User talk:Literaturegeek
Welcome!
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Benzos
Hi, thanks for your work on the benzodiazepine articles. You seem to be using footnotes a lot, but please make sure to use the correct templates. {{cite journal}} is for all journal articles; there is no need to tabulate all the parameters. In fact, this makes the editing box very hard to navigate. See the template page for some other recommendations. JFW | T@lk 20:44, 3 July 2007 (UTC)
You are welcome, I thought the nitrazepam article was not very well written and felt I would give a shot at enhancing it. Sorry first time editing and appears I didn't do quite as well as I expected. I did read about templates for references but see I didn't quite grasp how to do it properly. I believe I have managed to do it properly now. Thank you for pointing out my errors. Literaturegeek 21:59, 09 July 2007 (UTC)
MKULTRA
Re: Temazepam. At least some of your refs made it into the Temazepam article too. I propose to concentrate discussion common to all benzodiazepines in one place, for easier maintenance, instead of duplicating it over and over in all benzodiazepine articles. The Temazepam article is at least not what I want to read as a patient in e.g. a retirement home, when I look up the pills my doctor has given to me. I would think I have received a MKULTRA CIA brainwash drug, also used by KGB Russian prisons for torture, which will turn me into a vegetable and cause cancer, brainrot and testicular shrinkage. Also it will turn me into a CRIMINAL and JUNKIE in a "Jekyll and Hyde" manner. See discussion on Temazepam page. The discussion of dangers, obscure uses and misuses has to take up only an appropriate part of the article, if this is to be an encyclopedia of general importance. 70.137.178.160 (talk) 04:33, 4 April 2008 (UTC)
Quit stalking and harassing me and go away crazy man!!! I have had days and days of your wingeing like a baby. I had nothing to do with CIA mkultra edits, brainwashing etc to the temazepam article. Dry your eyes, quit crying, get over it and get a life or else take it up with the editor who made those edits and harass him/her instead of me. I didn't make those edits!!! I need a break from you crazy old man, I really really do. I am sorry but I am just sick of it. So please leave me alone.--Literaturegeek (talk) 05:45, 4 April 2008 (UTC)
Hi
I've left a note at Talk:Nitrazepam. Please try to tone down the stress level, and I believe both you and 70. would certainly benefit from walking away from benzo articles for a while. Fvasconcellos (t·c) 16:45, 4 April 2008 (UTC)
I appreciate doing that for me, if only you knew lol. I don't think he will stop. I doubt he will last 3 hours rather than 3 days. He is crazy...--Literaturegeek (talk) 16:48, 4 April 2008 (UTC)
Regarding Temazepam
Everything in the temazepam article is scientifically referenced. This anon user's edits will be reverted and he/she will be reported. I a pharmacology major, and drugs are what I study. User:thegoodson
Hi, Yeah I know it is all referenced. You did a good job on the article. I learnt quite a few things from it that I didn't previously know. I wasn't aware of it's use by the KGB and the CIA for example. Very interesting stuff. One point while I am chatting to you.
Do you have the full text of reference 37? This bit sounds like bad advice. Did they really say that in the fulltext or has that been just added in? I copied the text from the temazepam wiki article and put it in bold.
Gradual and careful reduction of the dosage, preferably with a milder long-acting benzodiazepine such as clonazepam or diazepam, or even a milder short to intermediate acting benzodiazepine such as oxazepam or alprazolam, was recommended to prevent severe withdrawal syndromes from developing. Other strong hypnotic benzodiazepines, whether short, intermediate or long-acting are not recommended.
Alprazolam and clonazepam are highly potent benzodiazepines. Alprazolam is renowned for causing withdrawal seizures. Usually it is chlordiazepoxide or diazepam only that is recommended for benzodiazepine withdrawal because they are long acting and available in small "low potency" dose sizes. Oxazepam is milder than most benzos but is very short acting. See this link. [1] and [2] and this link [3]. I think that the references used concerning withdrawing from temazepam could be improved or replaced with better ones. The reasons for using either chlordiazepoxide or diazepam can be backed up with common sense basic knowledge of pharmacology. The smallest dose of clonazepam is 0.5 mg which is equivalent to 10 mg of diazepam. You can't make small dose reductions with clonazepam.[4] Don't wanna post this on the talk page while that crazy anon user is about lol. What are your views?--Literaturegeek (talk) 10:05, 5 April 2008 (UTC)
- A little known secret is that temazepam was used in the research of mind control, brainwashing and mass-scale social engineering by Secret Intelligence agencies, including the KGB and the CIA. In the CIA, it was under code name MKSEARCH. It was used as a truth serum, it was used (in combination with other psychoactive drugs to try and brain wash people, it was used to keep Soviet dissidents in a constant vegetative state. This is part of the history of temazepam.
- Temazepam is an hypnotic benzodiazepine, and while many don't realize, temazepam and many other hypnotics such as nitrazepam and flunitrazepam may be less potent mg for mg than alprazolam or clonazepam, but their side effects are considerably more powerful. In the treatment of temazepam addiction, diazepam is recommended and is by far the most commonly used for such a purpose. In certain cases for certain individuals, clonazepam is recommended. However, short acting benzodiazepines can also be used and in certain cases, oxazepam, alprazolam, and bromazepam are used to manage withdrawals from hypnotic benzodiazepines. The hypnotic group is associated with a more severe withdrawal syndrome and permanent damage to the brain and many hypnotic abusers may develop speech or communication disorders, they have also been linked to cognition problems and balance disorders. Several of them (temazepam is among them) cause aphasia, dysnomia, delusional disorders, severe memory problems, motor coordination damage, and neurological problems. (read here: [5]). Alprazolam, though potent, is like M&M candies compared to temazepam and the hypnotics. The hypnotics are more akin to barbiturates in their ability to cause damage, addiction, and overdose.
- I spent a great deal of time working on the nitrazepam article aswell, so I hope this anon user doesn't mess with my work, which is scientifically referenced.
TheGoodSon 07:58, 06 April 2008 (UTC)
Yea, I agree it is an important part of the history and if people are insisting on it being removed from the article we should then be allowed to go and destroy the history section of LSD wiki history section of LSD to be neutral. I disagree still with you on alprazolam clonazepam. Clonazepam is in the same family of benzos as flunitrazepam (rohypnol) and nitrazepam because all 3 are nitrobenzodiazepines. Clonazepam is nitrazepam with a chlorine atom stuck on it, only real difference molecularly. Yea the benzos used for insomnia tend to be much more potent and have more profound toxicities and long term CNS damage associated with them. You do seem very knowledgable about the benzodiazepine class of drugs but disagree on one or two points but hey at least we can talk about it sensibly. There are comments awaiting for you on the temazepam talk page. The benzo articles are now at the attention of wikimed and wikipharm so we might end up getting a few editors involved to try and resolve the conflict with this anon user. The nitrazepam article is locked because the anon user kept undoing the reverts of his edits by an admin. At least we know about this class of drugs extensively and can back each other up against this anon user who I really think knows very little about these drugs.--Literaturegeek (talk) 13:12, 6 April 2008 (UTC)
- Hi, You are right that clonazepam is nitrobenzodiazepines and that it's closely related to nitrazepam and flunitrazepam, however that doesn't make its pharmacological profile, toxicity, or side effect profile like nitrazepam or flunitrazepam. All benzodiazepines have a similar mechanism of action and overall they all cause sedation, anxiolysis, and muscle relaxant properties, but not all are equally strong or profound in their ability to cause amnesia, sedation, motor-impairment, dependence, etc. You must realize that potency doesn't mean "stronger". Clonazepam is a strong anxiolytic and anticonvulsant, but a weak sedative. This is due to it being a stronger agonist of certain GABAA receptor subunits. Though all benzodiazepines are full agonists of the GABAA receptor, most of them are stronger agonists to certain subunits of the GABAA receptor subtypes. GABAA receptor mediation has tremendous impact on the pharmacological profile, clinical effects, and therapeutic purpose. The differences in anxiolytic, motor, subjective and reinforcing effects of benzodiazepines is all due to their differences in how how strong of agonists they are to certain GABAA receptor subunits. Clonazepam for example, is a strong anxiolytic because it is a strong agonist of the α2 and/or α3 subunits. Anticonvulsant action is mediated by a more then one subunit, but α3 plays a big part, as do other GABAA receptors (γ subunits maybe?). Temazepam, nitrazepam, flunitrazepam, nimetazepam, flutoprazepam, triazolam, loprazolam, and midazolam are the most powerful agonists of the α1 subunit amongst all benzodiazepines. The α1 mediates sedative-hypnotic effects, amnesia, ataxia, motor-impairment, and reinforcing behavior (which means these eight benzodiazepines are the most likely to be abused and produce dependence). Not only are they the most powerful α1 agonists, but they are all very strong α2, α3, and α5 (alpha 5 has to do with memory). The fact that these eight and most of the other hypnotics are usually strong agonists at all receptor subunits basically means that they are at least as strong of anxiolytics as any of the "anxiolytic benzodiazepines". Nimetazepam's anticonvulsant effects are much stronger than both lorazepam's and clonazepam's, in fact, nimetazepam is arguably the most powerful anticonvulsant BZD, only midazolam may be a contender. Temazepam and Nitrazepam have powerful anticonvulsant properties aswell, at least as powerful as clonazepam as anticonvulsants. Triazolam and midazolam will cause more sedation and amnesia than any of the non-hypnotic benzodiazepines. These eight, and all hypnotic benzodiazepines are also strong agonists of the ω1 subtype receptor (omega 1 receptor). Other very strong α1 subunit agonists are lormetazepam, estazolam, brotizolam, and flurazepam - but they still fall short of the top eight I mentioned above. Alprazolam and clonazepam and many of the non-hypnotics are relatively weak to mild agonists of the α1 subunit, though alprazolam is somewhat of a stronger agonist than clonazepam at that particular site. This is why alprazolam and clonazepam, despite their potency, are much milder than nitrazepam, temazepam, flutoprazepam or any of the rest I mentioned. I hope you can see what a drastic difference there is between the stronger hypnotics and the rest of the family of benzodiazepines. Hypnotics like quazepam, cinolazepam, and doxefazepam fall somewhere in between. As does diazepam.
- Also, most of those dependent on something like temazepam or nimetazepam have an extremely high tolerance, so reduction with clonazepam is a possibility, but it is not one that is mostly recommended and it's obviously not the best choice either. Tapering off of hypnotics with oxazepam or alprazolam are only meant to be a temporary thing. A dependence on a hypnotic benzodiazepine is often extremely difficult and physiologically damaging, so technically a taper with any non-hypnotic benzo or even one of the weaker hypnotic benzos, is possible just as a temporary measure. TheGoodSon 05:30, 08 April 2008 (UTC)
Hi goodson. Temazepam has strong amnesiac functions, as does flunitrazepam and nitrazepam. I wonder if it is the stronger deteriorating effects on cognitive functions which make these benzos particularly bad? It is something that I suspect. I am not sure if clonazepam has as strong effects on cognition as say lorazepam, flunitrazepam, temazepam, nitrazepam etc. You are right in what you say about the subunits and how they have differing effects. Yea it is mainly the alpha5 subunit which causes the amnesia side effects. I wonder if temazepam is a stronger agonist of the alpha5 subunit.
If a person is on a strong benzodiazepine, the way I manage it is to advise them to cross over gradually to diazepam (or if not diazepam chlordiazepoxide as a second line choice). If it is done gradually over a period of 4 - 12 weeks crossing a quarter of their dose or even an 8th of their dose at a time I would say about 95% of people can successfully cross over, including those on temazepam, nitrazepam and other benzos. The remaining 5% have to "file down" their sedative hypnotic or other benzo or else they have to find a compounding pharmacist to make up specialised dose capsules or liquid solution if they have a particularly strong physical dependence on their benzo. Complications occur I would say in about 50% of people and often failure occurs when the switch over is abrupt, such as suddenly switching say 4 mg of lorazepam for 40 mg of diazepam or 1 mg of clonazepam for 20 mg of diazepam overnight. It seems the "subtle" differences between the benzos in binding affinities can be felt quite intensely if their is a sudden change from one benzo to another. Another major problem as well is doctors who aren't familar with accurate equivalencies and use inaccurate equivalencies. Commonly doctors will think clonazepam 0.5 equals 5 mg of diazepam, instead of 10 mg or even less or doctors will try to "guess" the equivalency and this leads to disaster and failure to provocation of severe withdrawal effects. Half the time they diagnose these withdrawal syndromes as bipolar disorder and psychosis and so forth. You wouldn't believe how much of my work involves dealing with misdiagnosis for benzodiazepine withdrawal and some of the diagnosis given. Many end up on neuroleptics and all sorts of other drugs and told they need them for the rest of their life when all they suffered was benzo or ssri or alcohol withdrawal etc. When I am talking about potent benzodiazepines, I am usually but not always talking in terms of diazepam equivalents which I use regularly. So for example the smallest dose of alprazolam available is 0.25 mg which is equivalent to 5 mg of diazepam and the largest dose size available I think is 2 mg which is equivalent to 40 mg of diazepam. People are sometimes prescribed 8 mg of alprazolam (xanax) equivalent to 180 mg of diazepam. Same with clonazepam, smallest available dose size is 0.5 mg, equivalent to 10 mg of diazepam. Not good for tapering purposes because diazepam is available in 2 mg sized tablets, is very long acting and is also available in liquid form to make tiny reductions towards then end of a taper. I met a psychopharmacologist who was addicted to 100 mg of lorazepam once, 1000 mg of diazepam equivalent. There are reports in the medical literature of people abusing 2 or 3 thousand mg diazepam equivalent in the medical literature. One thing about benzo dependency especially in terms of drug abuse is if someone gets a serious drug abuse problem, there seems to be no "ceiling effect". The dose just keeps going up and up and up, not in everyone, in a small number of abusers. There does seem to be more of a limit with other drugs of misuse in what you commonly see, like there is usually a ceiling effect. I think that it is because tolerance to benzodiazepine agonists develops so rapidly often within days or weeks, especially to the sedative effects and often tolerance is complete and total without a dose increase. They are one of the fastest tolerance producing drugs. Didn't mean to write so much but oh well.--Literaturegeek (talk) 17:57, 9 April 2008 (UTC)
Re:Anon user
Personally I would like to see a resolution to this but I think you shouldn't be getting further drawn into this argument. I can't see how it can help matters. Most of the facts you initially answered and when it was obvious that this user was not listening there was little point in continuing. Unfortunately I don't have any particular knowledge of any of the administrators. I haven't got a very obvious presence on Wikipedia. So I can't help in that respect. My advice is just ignore this person. It's unnecessary putting this much time and effort fighting a cause into one user. My best advice on the topic would be just to ignore this user as there seems to be no reasoning with him/her.
While I will admit that the most of this anon users point were poor there was one argument that the user in question presented which showed some validity. This was the question of toxic doses in the rat experiments. This is a very messy area of pharmacology as it's very difficult to compare the metabolism of drugs on different animals. Most pharmacists and pharmacologists have limited knowledge in this area, myself included. This article may give some insight into the complexity of the area. The main reason for this complexity is because CYP50 compounds have been studied in far greater detail in humans than in animals. Also adding to this is differing physiologies of the species. e.g. The appendix is active in most wild creatures, cows have differing digestive systems, dogs are more susceptible to bromide toxicity etc.
Try not to let this sour your experience on wikipedia. If you manage to keep your cool with this you'll show you're the more rational individual. Medos (talk • contribs) 13:59, 5 April 2008 (UTC)
I would like to see a resolution to it as well with the troller and stalker banned. More drama now on the chlordiazepoxide page. I continue because I am trying to protect my reputation from this gibberish that this anon user talks about. They are making me famous on here. I will try and back away from them. Yea I know that animal studies are have their limitations and are sometimes not relevant to humans and that pharmacokinetics and multiple other reasons makes them difficult to interpret when compared to humans. Thanks for the link, I will give it a read. I do think that they do have some relevance because animal studies are used in FDA approval processes though and much of the psychopharmacological knowledge of receptor binding and other aspects of neuroscience comes from animal studies, especially mechanism of action of drugs.--Literaturegeek (talk) 21:03, 5 April 2008 (UTC)
- Studies are not only done on animal subjects, but homo sapiens are tested upon as well. Besides, the animal subjects aren't lab rats most of the time, contrary to what many believe. Baboons, Rhesus monkeys and other species of monkeys are often the main subjects of drug experimentation. Chimpanzees have been used in experimentation, but it is less prevalent nowadays due to the fact that chimps are so closely related to humans and as a result, experimentation on chimps is almost looked upon as a crime against humanity.
TheGoodSon 07:44, 06 April 2008 (UTC)
- I do agree that there is some middle ground between animal studies and human studies and they will as a general rule have similar effects. There is validity in animal studies when trying to design appropriate doses from phase 1 trials of drugs. It's just a science that isn't widely known. For instance I think that a lot of people would probably not realise that your average beagle metabolises some drugs closer to a human than a rhesus monkey. The main issue is that people have perceptions about this area, both positive and negative. Although I will admit that this caution generally applies more to newer drugs rather than established ones like benzodizapines. You're fact that lab rats aren't used most of the time is incorrect. In the UK in 2006 out of the 3.01 million procedures on living animals rats and mice accounted for 83% of them. Dogs, cats, horses and non-human primates accounted for less than 1% of the procedures conducted.see here It's an ethical nightmare to conduct trials on anything other than mice and rats. In fact you could argue that comparing phase 1 drugs trials to primates, humans are a less protected species. :) Medos (talk • contribs) 10:57, 6 April 2008 (UTC)
Please try to disengage
Literaturegeek, please stop responding to 70.'s edits with personal attacks and offensive remarks. If you feel upset or weirded out, try to disengage instead of escalating this. Fvasconcellos (t·c) 20:42, 5 April 2008 (UTC)
I will try again to ignor him. I am sorry, but I just get irritated by this person. Yes it is really weirding me out. I just want to return to the old days of wikipedia editing where I felt comfortable and edited in the peace and quiet I had without this person following my edits about and talking jibberish. I can't believe reviewers take this dude seriously. I am thinking of changing ISP's, maybe I can just disappear and create a new identity and not mention my old names? I know that is against the rules but if I am gonna have this stalker and admins are gonna let this weirdo constantly following me about going on and on and on about clutter and weirdo stuff, what choice do I have? There are other drugs that I have an interest in besides benzos. Perhaps I will disappear and come back on my new ISP with a new secret identity and edit a different class of drugs. I am running out of options. I will probably get banned at this rate anyway because I don't take too kindly to weirdo's following me about lol and it is simply not fair. Blah blah rant over sorry. Check my account(s), I have never been a troublemaker before. I edited in peace and when contacted was considerate in dealing with fellow editors and admins. I will try "disengaging" one more time.--Literaturegeek (talk) 20:50, 5 April 2008 (UTC)
Also, if I leave, no one will be checking on his edits and he will end up destroying a lot of articles. That is another reason that I am "fighting" with him. Fair enough these articles may not be class A or featured articles and thus have their issues but it doesn't mean you go on a rampage deleting huge blocks of text, article after article. Can you imagine how he would be left unchecked? Admins seem to think it is fine running about flagging article after article after article as disputed, getting them edit locked, deleting 2 thirds of an articles content with no discussion and filling talk pages up with jibberish.--Literaturegeek (talk) 20:56, 5 April 2008 (UTC)
- I'm sorry, but that's not the right approach. The anon's concerns are valid. Consensus should decide on whether the content he is removing belongs in the articles or not, and (a) it takes more than two to build consensus and (b) reverting one another is no use. If you keep adding back information you think is relevant, and he keeps removing it, nobody wins—least of all the people who are reading these articles on a daily basis and coming to Wikipedia for information—and you'll just keep going at each other in Talk pages. Fvasconcellos (t·c) 21:41, 5 April 2008 (UTC)
I understand consensus, but how to you reach consensus with someone who believes that all of his fellow nursing home residents worship a God with 5,000 heads and 10,000 ears? The whole nursing home have the same strange religion? I can try and reach consensus with a rational sane person nay problem whatsoever. Check my edits and the talk page of clonazepam, I tried to reach a consensus and gutted the clonazepam article myself but he was not happy he kept the argument going. He is way too weird.--Literaturegeek (talk) 21:45, 5 April 2008 (UTC)
I have begun conflict resolution, hopefully it will work this time. I am trying the calmer approach to try and get this resolved with the anon user and I have made some more compromise edits to clonazepam and chlordiazepoxide articles.--Literaturegeek (talk) 13:22, 6 April 2008 (UTC)
- Good—I'm sure you'll come to an agreement :) As an aside, I'd appreciate it if you could undo this edit. Although there is far more leeway regarding user pages, section headings should always be neutral (please see WP:USER and WP:TALK). Fvasconcellos* (t·c) 14:59, 6 April 2008 (UTC)
Cheers for bringing that to my attention. I decided to just remove the entire section as part of the deescalation of emotions and the situation.--Literaturegeek (talk) 15:15, 6 April 2008 (UTC)
Problem?
In case you missed it, I think something went wrong with this edit. No big deal. Angus McLellan (Talk) 17:22, 11 May 2008 (UTC)
- You're not the only one! I have the same troubles. Cheers, Angus McLellan (Talk) 17:34, 11 May 2008 (UTC)
I installed twinkle again and I think I have figured it out now. Take care and thanks for the message.--Literaturegeek | T@1k? 20:06, 12 May 2008 (UTC)
Reporting vandals
About you recent report to WP:AIV, it's no problem. One of the general prerequisites for reporting there is that the vandal must be active now, and have vandalised after sufficient recent warnings to stop. Thanks for reverting the vandalism and warning, though. Take care, -- Ed (Edgar181) 19:53, 12 May 2008 (UTC)
Thanks for the message and the information Edgar. Best wishes.--Literaturegeek | T@1k? 20:01, 12 May 2008 (UTC)
Toxicity of Benzos
Hi Literaturegeek, I myself have found conflicting research and data on the subject of teratogenic and carcinogenic effects of BZD's. Claims ranged from "none of the BZD's are carcinogenic" to "some may be, but very lightly", all the way to "all are". However, it seems that the very oldest BZD's (chlordiazepoxide, diazepam, nitrazepam, temazepam, flurazepam, oxazepam, etc) are the most notorious, but even within this group I have found mixed results. On the whole, I tend to agree with the notion that many of the older BZD's are carcinogenic and teratogenic. TheGoodSon 15:45, 13 May 2008 (UTC)
Thanks for the message. I agree with you regarding carcinogenicity. The literature on nitrazepam seems to be quite damning of that drug. I wonder if there would be any logic to the information in the genetic toxicity of the temazepam article being replaced with the information in the human toxicity section of the nitrazepam article? The information in the genetic toxicity section of the temazepam article doesn't mention temazepam but other benzodiazepines and this was one of the criticisms of that anon 70. user. The information in the nitrazepam article refers to benzodiazepines in general so is relevant to the temazepam article. The other idea, I am wondering is is it worth putting in the main benzodiazepine article? It is lacking information on carcinogenicity. What are your views?--Literaturegeek | T@1k? 07:35, 14 May 2008 (UTC)
- Nitrazepam does seem to be the worst. Almost all BZD's have a chlorine at the 7 position. Only 5 have a nitro group, those being nitrazepam, nimetazepam, flunitrazepam, loprazolam & clonazepam. 4 out of the 5 are hypnotics and all seem to be quite carcinogenic. Clonazepam is the "softest" of the 5. I took out the genetic toxicity sub-section of temazepam since it does seem to be a bit controversial. However, I do think that adding the carcinogenicity information to the main benzodiazepine article is a good idea because if I were to guess, I'd say that at least half (maybe more?) of the benzodiazepines are carcinogenic to some degree. It's relevent and important in my view. TheGoodSon 17:06, 16 May 2008 (UTC)
Oh I didn't know that loprazolam had a nitro group. So is it also classed as a nitrobenzodiazepine? Yea, probably about half being carcinogenic or more sounds right.--Literaturegeek | T@1k? 20:17, 16 May 2008 (UTC)
Loprazolam is an imidazobenzodiazepine with a nitro group. The nitro group gives it an extra kick that makes it a highly effective hypnotic. Nitrobenzodiazepines are nitrazepam, clonazepam, and flunitrazepam - as you know. Nimetazepam and menitrazepam also have nitro groups, but aren't classed as nitrobenzodiazepines. Since you work in addictions, I think the chemical structures of BZD's with a prominent N-methyl group might be of great interest to you. Nimetazepam has a nitro group, but like temazepam and lormetazepam, the N-methyl group is much more prominent. The amazing thing about nimetazepam is that if you look at the chemical structure, it almost looks like it was solely designed for the purpose of recreational drug abuse, moreso than even temazepam (as a result of that N-methyl + nitro group). A prominent N-methyl group seems to play a role with the abuse potential of benzos. The pharmacokinetic properties (absorption, distribution, metabolism, and excretion) of temazepam, nimetazepam, and lormetazepam make them highly likely to be misused.
- Benzos with their N-methyl analogues/derivatives:
- Nitrazepam ----> Nimetazepam (1964 synthesis)
- Lorazepam -----> Lormetazepam (methyl-lorazepam - 1984 synthesis?; lormetazepam is also the temazepam molecule with a orthochlorophenyl group, so it's equally a temazepam derivative as it is a lorazepam derivative)
- Oxazepam ------> Temazepam (1964 synthesis)
- Other benzos with an N-methyl group (less prominent):
- Nordazepam ----> Diazepam (diazepam has been heavily misused since its advent back in the early 60's)
If you notice, the methyl derivatives are ALL at least 150% as potent by weight . Ironically, not much in flunitrazepam's chemcial structure would suggest that it would be abuse prone - in fact, diazepam and nitrazepam show more prominent abuse potential. I'd say that this is one BZD that got "stoned" by the media. You might have already known this, but I thought it would be of interest to you. TheGoodSon 18:31, 19 May 2008 (UTC)
Thanks for the information. I was aware that modifications of chemical structures, even if they are slight can often change the potency and/or abuse potential of a drug significantly. This is true for other drug classes as you know such as opiates. Although I think you know more about the molecular make up of benzodiazepines than myself. I did a search and the only country where nimetrazepam is prescribed appears to be japan and perhaps a few other asian countries. Yea flunitrazepam got killed by the media, mostly as a date rape drug. Someone recently wrote something about the chemical structure of flunitrazepam and its potency and abuse potential on the talk page Talk:Flunitrazepam#similarity_to_mogadon_.28Nitrazapam.29. It can be difficult though to determine which benzo is the most abusable just based on which benzo is most abused in a country because the benzo which is most abused in a country is usually the benzo which is most prescribed. In the USA xanax is the most frequently prescribed benzo and is the most recreationally abused benzo. Xanax abuse in the UK for example is almost non-existent because it is rarely prescribed. It can only be prescribed privately over here. Diazepam and temazepam would be the main benzos of abuse in the UK now but they are the most commonly prescribed benzos.--Literaturegeek | T@1k? 22:42, 20 May 2008 (UTC)
Premazepam
Hi again, looks like you have added premazepam to the list of benzodiazepines. I have some research on that particular BZD here[6]. It seems like an interesting benzo. If you want to go ahead and summarize and add the information, please do. If you don't have the time right now, I will do it when I get the chance. It's not an urgent matter.
The crazy anon user has disappeared it seems. Well, I call this a victory for us. Hope we continue working together on improving the articles on benzodiazepines. We seem to be the most serious and active on them, though I have been quite busy with other things lately. I should be back on within the next few days to continue working on the articles. Right now, I am going to concentrate on expanding some of the articles on the newer or rare benzodiazepines (doxefazepam, meclonazepam, reclazepam, fludiazepam, etc) TheGoodSon 16:07, 13 May 2008 (UTC)
Thanks, I read that link and all of the other abstracts in pubmed on premazepam and added relevant ones to the premazepam article (there are only 9 abstracts listed in pubmed). It looks like it is a partial agonist of central benzodiazepine receptors, similar to flurazepam which is also a partial agonist. I summarised the information in it and added it to the premazepam article. I think partial agonists are less problematic than full agonists at least in terms of dependency, although I have known people who had a bad time coming off of flurazepam but I guess if they had a bad time coming off of flurazepam they would have had twice or perhaps 10 times the pain coming off of temazepam or nitrazepam, would be my guess. Well I suggest reading the last post I made to the anon user Talk:Clonazepam#ref.5B60.5D and you will see how I got rid of the anon user. It is very eye opening, when you read it. I have certainly learnt for the future how to deal with people like anon 70. I think that we were targeted by someone paid by Roche pharmaceuticals because we wrote factual peer reviewed information which they didn't like. One benzodiazepine that I think needs expanding on is lorazepam. It is a hypnotic benzodiazepine and I suspect if or when you research neurological damage from prolonged use and how quickly it induces dependency you will learn that it is on par with nitrazepam and temazepam. I am welcome to working along with you on the benzodiazepine articles. It will be interesting to see what information you pull up on the rarer benzodiazepines. I recently learnt that nordazepam (aka nordiazepam and aka desmethyldiazepam) is a partial agonist of the benzodiazepine receptor. I had assumed because it is an active metabolite of diazepam it would be a full agonist.--Literaturegeek | T@1k? 07:47, 14 May 2008 (UTC)
- It's almost hard to believe that flurazepam is only a partial agonist of the benzodiazepine receptors since first, it is an old generation BZD, and second, it's a sedative-hypnotic. Flurazepam has an interesting history among the benzos, especially for a partial agonist. Could it be that flurazepam is only antagonistic at certain receptor subtypes (or just at one receptor subtype)?
- Anyway, I did read your reply to that anon user. I laughed while reading it :). It's a possibility that he/she was a Roche employee since he/she came out of nowhere editing the articles. He/she was also quite immature - at one point he/she began to mock my ethnicity and than tried to discredit me by labelling me a "German nationalist".
- The newer/rare BZD's are very interesting. For example, meclonazepam has anti-parasitic properties. Some others seem to be pure anxiolytics without any of the other effects. Etizolam for example is supposed to be a very strong anxiolytic, stronger than alprazolam, clonazepam, and bromazepam. These benzos will likely displace many of the older ones as the years pass, much in the same way that zolpidem and zopiclone displaced temazepam, nitrazepam, and triazolam as first line hypnotics, and much in the same way that nitrazepam, temazepam, triazolam and flunitrazepam displaced barbiturates. TheGoodSon 17:38, 16 May 2008 (UTC)
Yea I was pretty shocked as well reading that flurazepam was a partial agonist. I referenced it in the flurazepam pharmacology section of the flurazepam article. Although it made sense. One lady who I was trying to help wean off of flurazepam said that she couldn't tolerate valium because it made her too sleepy. This was when she was swapping a quarter of a flurazepam tablet for an equivalent dose of valium. It answered my question. I am not sure about the binding affinities for flurazepam at the various alpha subunits and whether it is a full agonist or not for certain benzo receptor containing subunits. Yea I think roche. They attacked my nationality as well. They mocked britain on the librium talk page and scotland on the talk page and germany as you know on temazepam page. I do wonder was the anon trying to push you into a position into either attacking america or something to then get american wiki admins to turn against you and myself, knowing that there is a heavy USA presense on wikipedia? Or maybe they were just being immature. Or maybe I am being paranoid. If they come back I won't fall for any of their tricks. You should reference the antiparasitic properties of meclonazepam in its article. That is very interesting and I would like to read that. Yea you are probably right that more selective anxiolytics will replace the older benzodiazepines in the future.--Literaturegeek | T@1k? 20:41, 16 May 2008 (UTC)
Userboxes
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Hope these are what you were after :)Tresiden (talk) 17:07, 13 May 2008 (UTC)
Thank you! I replied on your talk page.--Literaturegeek | T@1k? 06:32, 14 May 2008 (UTC)
Thanks for welcoming
I appreciate your endeavours in pointing at the wiki guidelines. Take care :-) --Prowikia (talk) 10:40, 19 May 2008 (UTC)
You are very welcome.--Literaturegeek | T@1k? 22:28, 20 May 2008 (UTC)
Thank you for the welcome Literaturegeek- heh, I have to apologise for it being belated. I thought at first you might've been Wiki's own answer to Myspace's mythic 'Tom' but I'm glad to see otherwise :P Good luck with your projects. Adolon au (talk) 17:14, 21 May 2008 (UTC)
Ha, no I am not a bot, I am real. :P I don't use myspace but I assume that myspace's "Tom" is a welcoming bot.--Literaturegeek | T@1k? 16:39, 22 May 2008 (UTC)
Nitrazepam toxicity
I undid your undo, not because something was wrong, but just as a reminder for the discussion on the talk page, see there. It is not clear to me if the refs really have the general consequences as you stated, or if this is too fast and speculative. Take a look. (no kidding with the rat poison, but it points to a species dependent mechanism, at least a bit). Look at the dismutase stuff. Why doesn't that apply? Can you explain or have another ref at hand which leads to more general results? 70.137.145.75 (talk) 12:05, 3 June 2008 (UTC)
Anon
I gave it (don't know if it's a he or she) the 3RR. TheGoodSon 18:16, 18 June 2008 (UTC)
Good move.--Literaturegeek | T@1k? 18:18, 18 June 2008 (UTC)
I'm willing to discuss the article, but only when he/she decides to begin discussions. As of yet, he/she is only engaging in an edit war. TheGoodSon 18:26, 18 June 2008 (UTC)
The article is safe for now, but we should brace ourselves for his return shortly. TheGoodSon 18:36, 18 June 2008 (UTC)
- Brace yourselves for his return? Need I remind you that these are valid concerns? The three of you have broken 3RR in a matter of hours. This is absolutely unacceptable behavior, and I can't believe neither of you were blocked. Fvasconcellos (t·c) 19:44, 18 June 2008 (UTC)
You currently appear to be engaged in an edit war. Note that the three-revert rule prohibits making more than three reversions on a single page within a 24 hour period. Additionally, users who perform a large number of reversions in content disputes may be blocked for edit warring, even if they do not technically violate the three-revert rule. If you continue, you may be blocked from editing. Please do not repeatedly revert edits, but use the talk page to work towards wording and content that gains a consensus among editors. If necessary, pursue dispute resolution.
Please note that any future reverting of the anonymous editor will lead straight to a block, on any of the articles you have been arguing over. · AndonicO Engage. 21:32, 18 June 2008 (UTC)
- No, you misunderstood me (apologies for being unclear); if you revert again, be it tomorrow or in three months, you'll be blocked for 24 hours. Reason for that being that you already broke 3RR, I'm just leaving you unblocked so you can discuss. A 24-hour block won't solve anything right now. If nothing has been worked out a week from now, I'll extend the protection time. · AndonicO Engage. 11:44, 19 June 2008 (UTC)
But that means that the anon can edit at will unchallenged by me as I can never revert them. It is like the 3rr has been applied indefinitely, where now I am on a zero revert rule. If I revert one time any time in the future or near future (you say 3 months, what about 3 years?) I am blocked for 24 hours.--Literaturegeek | T@1k? 10:34, 20 June 2008 (UTC)
Twinkle removed
Literaturegeek, your use of Twinkle to revert-war on the Temazepam article, breaking the three-revert rule in under 15 minutes and labeling legitimate edits as vandalism—which is strictly and specifically defined on Wikipedia—shows me that you have understood neither this definition nor the value of staying cool when the editing gets hot. As clearly stated in WP:TW (in a big red box at the top of the page, no less), users must take full responsibility for all actions performed with the aid of Twinkle. I am not confident that you are able to exercise constraint at this moment and avoid further inappropriate use of TW, and I am therefore removing your access to the script for a period of two weeks. Please note that, if you start misusing Twinkle again when you regain access to it, you may lose this privilege indefinitely or be blocked without further warning.
Please also realize that this is not meant as punishment. It is a protective measure meant to prevent further edit warring and disruption. Fvasconcellos (t·c) 02:11, 20 June 2008 (UTC)
Replied here.User_talk:Fvasconcellos#Temazepam..--Literaturegeek | T@1k? 03:23, 20 June 2008 (UTC)
- OK, I've restored your Twinkle privileges. Please tread carefully, and remember Temazepam is still under 0RR. Best, Fvasconcellos (t·c) 22:05, 9 July 2008 (UTC)
Talkpages
The talkpage of an article is not the place for lengthy discussions of another editor's actions. If you wish wider community input on this editor, file a request for comment at Wikipedia:Requests for comment/User conduct. Any further off-topic posts on the tamazepam talkpage will be deleted. Please discuss the article and references. Nothing else. Tim Vickers (talk) 13:34, 21 June 2008 (UTC)
Sorry about that. I don't want to escalate things at the moment with the anon, so I won't file a request for comments. Thank you for your message.--Literaturegeek | T@1k? 14:12, 21 June 2008 (UTC)
- No problem, you're not the only one I've talked to about this. Hopefully if we concentrate only on the text and sources it will result in less heat and more light. Tim Vickers (talk) 14:22, 21 June 2008 (UTC)
Hitler
In the temazepam talk (now hidden) you claimed Hitler used water fluoridation to dumb people down. Where is this information from? Fluoridation is still done in the UK and the US. 70.137.161.241 (talk) 01:18, 22 June 2008 (UTC)
I have heard it in several places. I think the first time was in a DVD on fluoride someone gave me. I just did a google scholar search, lots of results there. I just found this link and learnt something new. [7] It looks like water fluoridation was first invented and used by the communist's in Russia before being adopted by Hitler as a way of making the masses docile, dumbed down and easily suggestable.--Literaturegeek | T@1k? 10:29, 22 June 2008 (UTC)
Why do you ask? Are you getting MKULTRA or MKSEARCH type mind control conspiracy theories into your head? :=) --Literaturegeek | T@1k? 11:26, 22 June 2008 (UTC)
Not really. The Wp article fluoridation doesn't mention it. They only talk about introduction since 1952. It is still done in UK and US. Now I know why my head feels so strangely hollow... I do however believe the Hitler story is a conspiracy theory too. (Aren't you living in UK?) 70.137.161.241 (talk) 14:36, 22 June 2008 (UTC)
Regarding the temazepam conspiracy theories and KGB/CIA stories: (I am taking this off the temazepam page, it really doesn't belong to the discussion there at the moment) It should be clear to you that in totalitarian states everything in the arsenal of a psych ward, and more, is being used to subdue people. It is not a surprise that temazepam was used in prison psych wards, probably along with everything else at the hands of the doctors. You can add this chapter to everything at the hands of a psychiatrist or anesthesiologist. Personally I believe the Scophedal is nicer for such purposes. Or JB329. Temazepam is just the lukewarm holy water, in comparison. Hell, it is sleeping pill for the old people, and drug of abuse for the kiddies, just not in same ballpark with real mindbenders. 70.137.161.241 (talk) 15:01, 22 June 2008 (UTC)
- Sounds like Godwin's law in action! :) Tim Vickers (talk) 17:12, 22 June 2008 (UTC)
I actually just spent 45 minutes looking into this (whether the nazis fluoridated the water, out of interest) and it looks like it is based on flimsy isolated statements in fringe books, so looks like it might not be true and is a conspiracy theory. the allegation is that fluoride was used to dumb down jews in at least one concentration camp. I should research things before I spout them as definitive fact. Anyway there have been studies that show increased thyroid disorders in places in America where water is fluoridated so I will stick to normal H20.--Literaturegeek | T@1k? 19:25, 22 June 2008 (UTC)
Anon you can't remove any edits done by thegoodson or myself from articles. We are all on a zero revert rule. You will get blocked for 24 hours if you undo or remove any edits we have done and vice versa.--Literaturegeek | T@1k? 19:28, 22 June 2008 (UTC)
What about above theory of totalitation drug use, Scophedal, JB329 etc. ? Do you really think the kiddie and grannie drug temazepam sticks out there? Obviously you are a little unaware of the possibilities? Temazepam is imo useless, the guy will just doze away. But e.g. the above will knock him out standing in a technical k.o. Then they will have him count the fingers and have a little heart to heart talk. 70.137.161.241 (talk) 00:09, 23 June 2008 (UTC)
http://www.springerlink.com/content/j130670641552610/
Seriously, what do you think they were trying to achieve here? (and related refs on the page)
If you are interested in such conspiracy theory and want the facts read
Franke, S.: Lehrbuch der Militärchemie; Band 1, Ost-Berlin, Militärverlag der Deutschen Demokratischen Republik
(Franke S.: Teaching book of military chemistry; Vol 1, East-Berlin, Military press of the German democratic republic.)
This is not fringe material but the std teaching book for the military academy on chemical (ehem!) agent, sabotage and subversion (ehem!) agent. For east german competent (ehem!) military and (ehem!) security people. They really didn't use kiddie and grannie pills, except maybe to relax and chill out themselves between (ehem!) heart to heart talks. 70.137.161.241 (talk) 21:27, 25 June 2008 (UTC)
Page unprotection?
Hi there, I've raised the possibility of unprotecting the tamazepam page here. What are your thoughts? Tim Vickers (talk) 17:03, 22 June 2008 (UTC)
- I see you're still worried about this. What are your concerns? Are you worried that edit warring will break out again? I think that I'd make it a condition of unprotection that anybody edit-warring will be blocked immediately. Tim Vickers (talk) 21:00, 22 June 2008 (UTC)
No, I was neutral because of what Fvasconcellos said about thegoodson not having been around is all.--Literaturegeek | T@1k? 10:53, 23 June 2008 (UTC)
- I've unprotected it, please edit slowly. I'd recommend redrafting sections one at a time on the talkpage, like we're doing with the tolerance one at the moment. Tim Vickers (talk) 21:07, 23 June 2008 (UTC)
Reverts
You have reverted 2 of my edits.
1. Clorazepate. I have correctly cited against the ref of the statement. You say I have to provide a citation of the follow up study. Its already there in your ref. Read it. Don't revert me. 0RR.
2. Flurazepam Already agreed on the Temazepam page. Unspecific to Flurazepam, is about sedatives in general. Tangential to Flurazepam. Again: Don't REVERT me.
Put those back. 70.137.181.232 (talk) 23:00, 14 July 2008 (UTC)
You broke the 0RR by manually deleting/reverting text first without discussing on the talk page. Anyway keep your hair on. I read what you wrote on the talk page after I asked you to write on the talk page and can see the validity of that edit to clorazepate and agree with it.
As for the elderly section of the temazepam article which was deleted. I scrolled down the temazepam page and it was not discussed unless I missed it. Please tell me the title of the section that it was discussed in. It is relevant to flurazepam, the review includes flurazepam. Review papers are actually considered a strong evidence base on wikipedia. It was deleted off of temazepam because a single short sentence in the paragraph was the same as in the abstract, I really don't know why it couldn't have been reworded in the temazepam article rather than deleting it. It takes all of 5 seconds. Oh yea bias, any excuse to delete stuff eh.--Literaturegeek | T@1k? 00:22, 15 July 2008 (UTC)
It was deleted because 1. copyvio 2. it doesn't belong there anyway.
Nobody protested, neither did I. I agree the copyvio could have easily been fixed, but it is not the important point. The impotant point is similar to the benzodiazepines committee. As it stands it applies to practically all sedatives, is unspecific to flurazepam, doesn't address the specific problem of its long halflife and possible consequences.
I agree that for flurazepam it could be more important than for temazepam, because of long halflife and consequently possible accumulation. But flurazepam is also more lipid soluble than temazepam, so redistribution into a larger volume plays more of a role. I don't know how the steady state looks. I agree it is a concern. But the reference is much too general there.
But I don't think it justifies a whole chapter, more a short warning about possible accumulation and resulting daytime impairment, as well as general mention that it is not intended for long-term use.
A completely general discussion of the caveats of sedative use in the elderly is IMO overdone and then tangential to the article. Even more so the discussion what could be done, used, developed instead and what other drugs share the same problems. This is not a teaching book of geriatric sleep medicine. The reference could however be used in the short discussion to be inserted in side effects. Just my lay opinion. 70.137.181.232 (talk) 08:17, 15 July 2008 (UTC)
A more detailed chapter on pharmacokinetics of flurazepam, including redistribution effects and eventually active metabolites could also be included. I have no such reference, but I am sure if we find a good one it will also include a discussion of the elimination and accumulation in the elderly and resulting problems. If you find such more specific reference it would be much better. 70.137.181.232 (talk) 08:32, 15 July 2008 (UTC)
Maybe this is a good start http://www.rxlist.com/cgi/generic/fluraz_cp.htm Of course all the general considerations, no long term use recommended, careful with daytime aftereffects etc. apply. But this one is a bit more specific. Looks like the long lived part is the N1-desalkyl metabolite. (active). The other metabolite N1-hydroxyethyl-derivative is also active I think, and is a hypnotic, I guess. This and the flurazepam itself seem to have surprisingly short apparent halflives. The N1-desalkyl metabolite is I think more lipid soluble and has a larger distribution volume, I guess in my lay brain. It also has more the pharmacological properties of a day tranquilizer, namely long halflife and little hypnotic effect, I guess, so that it does make less sleepy than flurazepam itself, but prevents daytime rebound anxiety and withdrawal symptoms, I guess. 70.137.181.232 (talk) 11:57, 15 July 2008 (UTC)
So I can only guess that the goal of this drug design was to have a "two-in-one" combination of a short lived hypnotic and a long lived anxiolytic day tranquilizer. And with that profile it differs markedly from some other hypnotics. However, temazepam seems to embody a similar trick, namely the metabolite of N1-demethylation is desmethyl-temazepam=oxazepam. The O-conjugate of desmethyl-temazepam is excreted as a minor metabolite. (7%) How far this contributes to day time aftereffects I do not know. 70.137.181.232 (talk) 12:10, 15 July 2008 (UTC)
clorazepate
Your ref says tranxene 7.5mg discontinued. What about the others? 70.137.181.232 (talk) 20:42, 20 July 2008 (UTC)
I didn't write that although I found a source for it. I know that it is still available in the USA.--Literaturegeek | T@1k? 04:45, 21 July 2008 (UTC)
To be precise with that ref we can only say Clorazepate 7.5mg was removed. I wonder if the others are still available in UK. 70.137.181.232 (talk) 08:12, 21 July 2008 (UTC)
It has been completely removed from the UK market. I think only 7.5 mg tablets were available. I updated with a better reference which mentions product license removal.--Literaturegeek | T@1k? 21:53, 23 July 2008 (UTC)
Sounds implausible to me as the 7.5mg is a really low dose. Can you check against the national formulary (unaware how this is called in your neck of the woods), if others were licensed, on private prescription maybe? I am aware that the UK system is a bit complicated because of the state run system, in parallel with private presciptions. 70.137.181.232 (talk) 05:14, 24 July 2008 (UTC)
It is not listed in the British National Formulary, I checked both online [8] and in the BNF handbook. It is not available on private prescription either. Once a product license has been removed the drug is no longer available.--Literaturegeek | T@1k? 18:37, 24 July 2008 (UTC)
eszopiclone
Obviously you are not reading the refs. You just restored vandalism about "penis enlargement in males" etc., the ref doesn't mention that with a word. (Wasn't my edit however, but I give up the hope for Wikipedia as long as immature vandals are editing) 70.137.181.232 (talk) 20:54, 20 July 2008 (UTC)
Thank you anon, I fixed it, although the edit I reverted was also inappropriate editing. I know the feeling about editing here.--Literaturegeek | T@1k? 04:44, 21 July 2008 (UTC)
You are welcome. Still think I am a vandal/troll? 70.137.181.232 (talk) 08:12, 21 July 2008 (UTC)
I think your edits have been quite productive recently. I do worry is this the calm before the storm! :=)--Literaturegeek | T@1k? 21:34, 23 July 2008 (UTC)
My edits have been productive from the beginning. I have only applied much more stringent criteria for evidence and notability, than it was done before. In several cases I have done bold edits to get a discussion. It would be far from my intention to vandalize articles. I am also not "immature" or in any way mental, neurotic, senile or paid by somebody. You just didn't see immediately what I was doing. If you give the temazepam article a look, it is now much more organized, concise and armor plated with refs, which actually are cited to the iota. It needs however some more work on the open points which have maintenance tags on them and then a final polishing. I assume in your favor that you didn't read most references. What you have watched is not POV pushing, disguised by seemingly plausible arguments, but it is the methodical work I am used to. I admit that I am rather anal in removing free interpretation and WP:SYN. Where you thought I am applying original research, I actually only mentioned my impression as a running comment on the talk, but never used it to justify edits. The justification of edits has always been done in a methodical, almost algorithmic fashion. If you have the nerve to read it, I will be glad to write it up, you can scrutinize every of my edits and discuss it with me. I have given the article the meat grinder. If we continue to work on it, it can become a good article. Isn't that what you want? 70.137.181.232 (talk) 04:30, 24 July 2008 (UTC)
I do not think that you are immature, senile, mental or neurotic anymore. You have said yourself that you were involved in research and development of drugs in a laboratory setting as a neuroscientist for 36 years. So which drug company I guess I am wondering you worked in for 36 years? Yea I want a good article.--Literaturegeek | T@1k? 18:40, 24 July 2008 (UTC)
Oh, this is feature creep. I said I have worked in R&D for 35 years. But not for a drug company and not as a neuroscientist. Then let us continue to improve articles. 70.137.181.232 (talk) 22:51, 24 July 2008 (UTC)
Hey there
Good work on Barbiturate :) Fvasconcellos (t·c) 14:18, 25 July 2008 (UTC)
Thank you FV. :=) --Literaturegeek | T@1k? 17:00, 25 July 2008 (UTC)
What is childish bullshit wrt. original Edgewood Arsenal records, EA-3167 and a link to the Academy Press? After we had a long fight about temazepam as an interrogation drug (allegedly), which was really bullshit. 70.137.164.136 (talk) 00:18, 1 August 2008 (UTC)
Read this: