Depressant
A depressant, or central depressant, is a drug that lowers neurotransmission levels, which is to depress or reduce arousal or stimulation, in various areas of the brain.[1] Depressants are also colloquially referred to as downers as they lower the level of arousal when taken. Stimulants or "uppers" increase mental or physical function, hence the opposite drug class of depressants is stimulants, not antidepressants.
Depressants are widely used throughout the world as prescription medicines and as illicit substances. Alcohol is a very prominent depressant. Alcohol can be and is more likely to be a large problem among teenagers and young adults. When depressants are used, effects often include ataxia, anxiolysis, pain relief, sedation or somnolence, and cognitive or memory impairment, as well as in some instances, euphoria, dissociation, muscle relaxation, lowered blood pressure or heart rate, respiratory depression, and anticonvulsant effects. Depressants also act to produce anesthesia. Cannabis may sometimes be considered a depressant due to one of its components, cannabidiol. The latter is known to treat insomnia, anxiety and muscle spasms similar to other depressive drugs. However, tetrahydrocannabinol, another component, may slow brain function to a small degree while reducing reaction to stimuli, it is generally considered to be a stimulant and main psychoactive agent to sometimes cause anxiety, panic and psychosis instead. Other depressants can include drugs like Xanax (a benzodiazepine) and a number of opioids. Gabapentinoids like gabapentin and baclofen are depressants and have anticonvulsant and anxiolytic effects. Most anticonvulsants like Lamotrigine and Phenytoin are depressants. Carbamates (Felbamate Carisoprodol) are depressants that are similar to barbiturates.
Depressants exert their effects through a number of different pharmacological mechanisms, the most prominent of which include facilitation of GABA, and inhibition of glutamatergic or monoaminergic activity. Other examples are chemicals that modify the electrical signaling inside the body, the most prominent of these being bromides and channel blockers.
Indications
Depressants are used medicinally to relieve the following symptoms:
- Anxiety disorders such as:
- Insomnia
- Obsessive–compulsive disorder
- Seizures
- Convulsions
- Depression
- Pain
Types
Alcohol
![](http://upload.wikimedia.org/wikipedia/commons/thumb/7/7a/Alcoholic_beverages.jpg/220px-Alcoholic_beverages.jpg)
An alcoholic beverage is a drink that contains alcohol (also known formally as ethanol), an anesthetic that has been used as a psychoactive drug for several millennia. Ethanol is the oldest recreational drug still used by humans. Ethanol can cause alcohol intoxication when consumed. Alcoholic beverages are divided into three general classes for taxation and regulation of production: beers, wines, and spirits (distilled beverages). They are legally consumed in most countries around the world. More than 100 countries have laws regulating their production, sale, and consumption.[2]
The most common way to measure intoxication for legal or medical purposes is through blood alcohol content (also called blood alcohol concentration or blood alcohol level). It is usually expressed as a percentage of alcohol in the blood in units of mass of alcohol per volume of blood, or mass of alcohol per mass of blood, depending on the country. For instance, in North America a blood alcohol content of "0.10" or more correctly 0.10 g/dL means that there are 0.10 g of alcohol for every dL of blood (i.e., mass per volume is used there).[3]
Barbiturates
Barbiturates are effective in relieving the conditions that they are designed to address (insomnia, seizures). They are also commonly used for unapproved purposes, are physically addictive, and have serious potential for overdose. In the late 1950s, when many thought that the social cost of barbiturates was beginning to outweigh the medical benefits, a serious search began for a replacement drug. Most people still using barbiturates today do so in the prevention of seizures or in mild form for relief from the symptoms of migraines.
Benzodiazepines
![](http://upload.wikimedia.org/wikipedia/commons/thumb/1/12/Xanax_2_mg.jpg/220px-Xanax_2_mg.jpg)
A benzodiazepine (sometimes colloquially "benzo"; often abbreviated "BZD") is a drug whose core chemical structure is the fusion of a benzene ring and a diazepine ring. The first such drug, chlordiazepoxide (Librium), was discovered accidentally by Leo Sternbach in 1955, and made available in 1960 by Hoffmann–La Roche, which has also marketed the benzodiazepine diazepam (Valium) since 1963.
Benzodiazepines enhance the effect of the neurotransmitter gamma-aminobutyric acid (GABA) at the GABAA receptor, resulting in sedative, hypnotic (sleep-inducing), anxiolytic (anti-anxiety), anticonvulsant, and muscle relaxant properties; also seen in the applied pharmacology of high doses of many shorter-acting benzodiazepines are amnesic-dissociative actions. These properties make benzodiazepines useful in treating anxiety, insomnia, agitation, seizures, muscle spasms, alcohol withdrawal and as a premedication for medical or dental procedures. Benzodiazepines are categorized as either short-, intermediate-, or long-acting. Short- and intermediate-acting benzodiazepines are preferred for the treatment of insomnia; longer-acting benzodiazepines are recommended for the treatment of anxiety.
In general, benzodiazepines are safe and effective in the short term, although cognitive impairments and paradoxical effects such as aggression or behavioral disinhibition occasionally occur. A minority react reverse and contrary to what would normally be expected. For example, a state of panic may worsen considerably following intake of a benzodiazepine. Long-term use is controversial due to concerns about adverse psychological and physical effects, increased questioning of effectiveness, and, because benzodiazepines are prone to cause tolerance, physical dependence, and, upon cessation of use after long-term use, benzodiazepine withdrawal syndrome. Due to adverse effects associated with the long-term use of benzodiazepines, withdrawal from benzodiazepines, in general, leads to improved physical and mental health. The elderly are at an increased risk of experiencing both short- and long-term adverse effects.
There is controversy concerning the safety of benzodiazepines in pregnancy. While they are not major teratogens, uncertainty remains as to whether they cause cleft palate in a small number of babies and whether neurobehavioural effects occur as a result of prenatal exposure; they are known to cause withdrawal symptoms in the newborn. Benzodiazepines can be taken in overdoses and can cause dangerous deep unconsciousness. However, they are much less toxic than their predecessors, the barbiturates, and death rarely results when a benzodiazepine is the only drug taken; however, when combined with other central nervous system depressants such as alcohol and opiates, the potential for toxicity and fatal overdose increases. Benzodiazepines are commonly misused and taken in combination with other addictive drugs. In addition, all benzodiazepines are listed in Beers List, which is significant in clinical practice.
Cannabis
Cannabis is often considered either in its own unique category or as a mild psychedelic.[4][5] The chemical compound tetrahydrocannabinol (THC), which is found in cannabis, has many depressant effects such as muscle relaxation, sedation, decreased alertness, and less tiredness.[citation needed] Contrary to the previous statement, activation of the CB1 receptor by cannabinoids causes an inhibition of GABA, the exact opposite of what central nervous system depressants do.[6]
Carbamates
Carbamates are a class of depressants or "tranquilizers" that are synthesized from urea.[7] Carbamates have anxiolytic,[8] muscle relaxant,[8] anticonvulsant,[9] hypnotic,[8] antihypertensive,[10] and analgesic effects. It has other uses like muscle tremors, agitation, and alcohol withdrawal. It's muscle relaxant effects are useful for strains, sprains, and muscle injuries together with rest, physical therapy, and other measures.[8] The effects, synthesis and mechanism of action of Carbamates are very similar to barbiturates.[11] There are many different types of Carbamates, some only produce anxiolytic effects and hypnotic effects while some only have anticonvulsant effects.
Side effects of Carbamates include drowsiness, dizziness, headache, diarreha, nausea, flatulence, liver failure, poor coordination, nystagmus, abuse, dizziness, weakness, nervousness, euphoria, overstimulation and dependence. Uncommon but potentially severe adverse reactions include hyper sensivity reactions including Stevens Johnson syndrome, embryo-fetal toxicity, stupor, and coma. Carbamates are fatal in overdose, which is why a lot of them have been replaced with benzodiazepines. It is not recommended to use most Carbamates like Carisoprodol for a long time as physical and psychological dependence does occur.[12]
Meprobamate which metabolizes to Carisoprodol was launched in 1955. It quickly become the first blockbuster psychotropic drug in America becoming popular in Hollywood and gaining fame for its seemingly miraculous effects. It has since been marketed under more than 100 trade names, from Amepromat through Quivet to Zirpon. Carisoprodol, which is still used today mainly for it's muscle relaxant effects has high abuse potential. It's mechanism of action is very similar to barbiturates, alcohol, methaqualone and benzodiazepines. Carsidoprodol allosterically modulates and directly activates the human α1β2γ2 GABAAR (GABAA) in the central nervous system in a barbiturate-like manner. This causes chloride channels to open, allowing chloride to flood into the neuron, slowing down communication betwen neurons; thus slowing down the nervous system.[13] Unlike benzodiazpines which increase the frequency of the chloride channel opening, Carisoprodol increase the duration of channel opening when GABA is bound.[14][15] GABA is the main inhibitory neurotransmitter in the nervous system, which causes its depressant effects.
Carbamates are fatal in overdose. Symptoms are similar to a barbiturate overdose. Symptoms typically include difficulty thinking, poor coordination, decreased level of consciousness, and a decreased effort to breathe (respiratory depression). An overdose is more likely to be fatal when it is mixed with another depressant that suppresses breathing. Death occurs this is typically due to a lack of breathing.
Physical and psychological dependence does happen with long term use of Carbamates; particularly Carisoprodol. Today Carisoprodol is only used short term for muscle pain, particularly back pain. Discontuation after long term use could be very intense and even possibly fatal. Withdrawal can resemble barbiturate, alcohol, or benzodiazepine withdrawal, as they all have a similar mechanism of action. Discontinuation symptoms include, confusion, disorientation, delirium, hallucinations (auditory & visual), insomnia, decreased appetite, anxiety, psychomotor agitation, pressured speech, tremor, tachycardia, seizures which could be fatal.[16]
Carbamates we're popular in the 1950's along with barbiturates. Although they have been slowly phased out; mainly due to the overdose and dependence risks, new derivates still exist. Felbamate is an anticonvulsant that was approved in 1993 that is commonly used today. It is a GABAA positive allosteric modulator and blocks the NR2B subunit of the NMDA receptor. Some carbamates block sodium channels. Phenprobamate was used as an anxiolytic and is still sometimes used in Europe for general anesthesia and for treating muscle cramps and spasticity. Methocarbamol is a popular drug that is commonly known as Robaxin, that is over the counter in some countries.. It is a carbamate with muscle relaxant effects. Tetrabamate; a is a controversial drug which is a combination of febarbamate, difebarbamate, and phenobarbital which is marketed in Europe was largely but not completely discontinued. April 4, 1997 after over 30 years of use due to reports of hepatitis and acute liver failure. The decision to restrict the use of the drug had been long-awaited. Carisoprodol; known as, "Soma" is still commonly used today for it's muscle relaxant effects. It is also very commonly abused around the world. It is a Schedule IV substance in the United States. Famous martial artist and actor Bruce Lee died due to an allergic reaction to meprobamate.
Approved
- Carisoprodol/Meprobamate/Tybamate (Soma/Miltown, Solacen) (muscle relaxant, anxiolytic, tranquilizer)
- Difebarbamate (Atrium, Sevrium) (tranquilizer)
- Emylcamate (Striatran) (anxiolytic and muscle relaxant)
- Ethinamate (Valamin, Valmid) (sedative-hypnotic)
- Febarbamate/Phenobamate (Solium, Tymium) (anxiolytic and tranquilizer)
- Felbamate (Felbatol) (anticonvulsant)
- Hexapropymate (Merinax) (hypnotic-sedative)
- Mebutamate (Capla, Dormate) (anxiolytic, sedative, antihypertensive)
- Phenprobamate (Gamaquil, Isotonil) (muscle relaxant, sedative, anxiolytic, anticonvulsant, anesthesia)
- Procymate (Equipax) (sedative, anxiolytic)
- Styramate (Sinaxamol) (muscle relaxant, anticonvulsant)
- Tetrabamate (febarbamate, difebarbamate, phenobarbital) (Atrium, G Tril, Sevrium) (anxiety, alcohol withdrawal, muscle tremors, agitation, depression)
Although a drug may be approved, it does not necessarily mean it is still used today.
Not approved
- Carisbamate (anticonvulsant)
- Clocental (hypnotic)
- Cyclarbamate (muscle relaxant and tranquilizer)
- Lorbamate (muscle relaxant and tranquilizer)
- Nisobamate (tranquilizer)
- Pentabamate (tranquilizer)
Gabapentinoids
Gabapentinoids are a unique and relatively novel class of depressants that selectively bind to the auxiliary α2δ subunit (CACNA2D1) and (CACNA2D2), site of certain VDCCs, and thereby act as inhibitors of α2δ subunit-containing Voltage-gated calcium channels. α2δ is nicknamed the "Gabapentin receptor". At physiologic or resting membrane potential, VDCCs are normally closed. They are activated (opened) at depolarized membrane potentials and this is the source of the "voltage-gated" epithet. Gabapentinoids bind to the α1 and α2 sites of the α2δ subunit family. Gabapentin is the prototypical gabapentinoid. The α2δ is found on L-type calcium channels, N-type calcium channels, P/Q-type calcium channels, and R-type calcium channels throughout the central and peripheral nervous systems. α2δ is located on presynaptic neurons and affects calcium channel trafficking and kinetics, initiates extracellular signaling cascades, gene expression and promotes excitatory synaptogenesis through thrombospondin 1 .[17] Gabapentinoids are not direct channel blockers, instead they disrupt the regulatory function of α2δ and its interactions with other proteins. Most of the effects of gabapentinoids are mediated by the high voltage activated N and P/Q-type calcium channels. P/Q-type calcium channels are mainly found in the cerebellum (Purkinje neurons) which made be responsible for the ataxic adverse effect of gabapentinoids, while N-type calcium channels are located throughout the central and peripheral nervous systems. N-type calcium channels are mainly responsible for the analgesic effects of gabapentinoids. Ziconotide, a non-gabapentinoid ω-conotoxin peptide binds to the N-type calcium channels and has analgesic effects 1000 times stronger than morphine. Gabapentinoids are selective for the α2δ site, but non-selective when they bind to the calcium channels complex. They act on the α2δ site to lower the release of many excitatory and pro-nociceptive neurochemicals including glutamate, substance P, calcitonin gene-related peptide (CGRP) and more.[18][19][20]
Gabapentinoids are absorbed from the intestines mainly by the Large neutral amino acid transporter 1 (LAT1, SLC7A5) and the Excitatory amino acid transporter 3 (EAAT3). They are one of the few drugs that use these amino acid transporters. Gabapentinoids are structurally similar to the Branched-chained amino acids L-leucine, and L-isoleucine, both of which also bind to the α2δ site. Branched-chained amino acids like l-leucine, l-isoleucine, and l-valine have many functions in the central nervous system. They modify large neutral amino acid (LNAA) transport at the blood–brain barrier, and reduce the synthesis neurotransmitter of neurotransmitters derived from aromatic-amino acids notably serotonin from tryptophan, and catecholamines from tyrosine and phenylalanine.[21] This may be relevant to the pharmacology of gabapentinoids.
Gabapentin was designed by researchers at Parke-Davis to be an analogue of the neurotransmitter GABA that could more easily cross the blood–brain barrier and was first described in 1975 by Satzinger and Hartenstein.[22][23] Gabapentin was first approved for epilepsy, mainly as an add-on treatment to partial seizures. Gabapentinoids are GABA analogues,[24] but they do not bind to the GABA receptors, do not convert into GABA or another GABA receptor agonist in vivo, and do not directly modulate GABA transport or metabolism.[25][26] Phenibut and baclofen, two structurally related compounds are exceptions as they mainly act on the GABA B receptor.[27][28] Also, gabapentin, but not pregabalin, has been found to activate Kvvoltage-gated potassium channels (KCNQ). Despite this, gabapentinoids mimic GABA activity by inhibiting neurotransmission.[29] Gabapentinoids prevent delivery of the calcium channels to the cell membrane, and disrupt interactions of α2δ with NMDA receptors, AMPA receptors, neurexins, and thrombospondins. Some calcium channel blockers of the dihydropyridine class used for hypertension weakly block α2δ.[30]
Gabapentinoids have anxiolytic, anticonvulsant, antiallodynic, and antinociceptive properties.[19][31][32] Pregabalin and gabapentin are used in epilepsy, mainly partial seizures (focal). Gabapentinoids are not effective for generalized seizures. They are also used for postherpetic neuralgia, neuropathic pain associated with diabetic neuropathy, fibromyalgia, generalized anxiety disorder, and restless legs syndrome.[33][34][35][36][37][38] Pregabalin and gabapentin have many off-label uses including insomnia,[39] Alcohol and opioid withdrawal,[40] smoking cessation,[41] social anxiety disorder,[42] bipolar disorder,[43][44] attention deficit hyperactivity disorder,[45] chronic pain, hot flashes,[46] migraines and more. Baclofen is primarily used for the treatment of spastic movement disorders, especially in instances of spinal cord injury, cerebral palsy, and multiple sclerosis.[47] Phenibut is used in Russia, Ukraine, Belarus and Latvia to treat anxiety and to improve sleep, as in the treatment of insomnia.[48] It is also used for various other indications, including the treatment of asthenia, depression, alcoholism, alcohol withdrawal syndrome, post-traumatic stress disorder, stuttering, tics, vestibular disorders, Ménière's disease, dizziness, for the prevention of motion sickness, and for the prevention of anxiety before or after surgical procedures or painful diagnostic tests.[48] Phenibut, like other GABA B agonists, is also sometimes used by body builders to increase human growth hormone.
Reuters reported on 25 March 2010, that "Pfizer Inc violated a United States racketeering law by improperly promoting the epilepsy drug Neurontin (gabapentin). Under the Racketeer Influenced and Corrupt Organizations Act the penalty is automatically tripled, so the finding will cost Pfizer $141 million." The case stems from a claim from Kaiser Foundation Health Plan Inc. that "it was misled into believing Neurontin was effective for off-label treatment of migraines, bipolar disorder and other conditions. Pfizer argued that Kaiser physicians still recommend the drug for those uses", and that "the insurer's website also still lists Neurontin as a drug for neuropathic pain."
In some cases, gabapentinoids are abused and provide similar effects to alcohol, benzodiazepines and gamma-hydroxybutyric acid (GHB).[49][50][51] The FDA placed a black box warning on Neurontin (gabapentin), and Lyrica (pregabalin), for serious breathing problems.[52] Mixing gabapentinoids with opioids, benzodiazepines, barbiturates, GHB, alcohol, or any other depressant is potentially deadly.[53][54][55][56]
Common side effects of gabapentinoids include drowsiness, dizziness, weakness, increased appetite, urinary retention, shortness of breath, involuntary eye movements (nystagmus), uncontrollable jerking motions, auditory hallucinations, erectile dysfunction, and myoclonic seizures.[57][58]
An overdose of gabapentinoids usually consists of severe drowsiness, severe ataxia, blurred vision, slurred speech, severe uncontrollable jerking motions, and anxiety.[59][60] Like most anticonvulsants, pregabalin and gabapentin have an increased risk of suicidal thoughts and behaviors.[61][62] Gabapentinoids, like all calcium channel blockers are known to cause angioedema.[63] Taking them with an ACE inhibitor can increase the toxic effects of Gabapentinoids.[64] They may also enhance the fluid-retaining effect of certain anti-diabetic agents (thiazolidinediones). It is not known if they cause gingival enlargement like other calcium channel blockers. It is unclear if it is safe to use Gabapentinoids during pregnancy with some studies showing potential harm.[65]
Physical or physiological dependence does occur during long-term use of gabapentinoids.[66] Following abrupt or rapid discontinuation of pregabalin and gabapentin people report withdrawal symptoms like insomnia, headache, nausea, diarrhea, flu-like symptoms, anxiety, depression, pain, hyperhidrosis, seizures, psychomotor agitation, confusion, disorientation, and gastrointestinal complaints.[67][68] Acute withdrawal from baclofen and phenibut may also cause auditory and visual hallucinations, and acute psychosis.[69][70] Baclofen withdrawal can be more intense if it is administered intrathecally or for long periods of time. If Baclofen or Phenibut is used for long periods of time it can resemble intense benzodiazepine, GHB or alcohol withdrawal. To minimize withdrawal symptoms Baclofen or Phenibut should be tapered down slowly. Abrupt withdrawal from Phenibut or Baclofen could be possibly be life-threatening, because of it’s mechanism of action. Abrupt withdrawal can cause rebound seizures and severe agitation.[71][70]
- Gabapentin (Neurontin)
- Gabapentin Enacarbil (Horizant, Regnite)
- Gabapentin Extended-Release (Gralise)
- Pregabalin (Lyrica)
- Phenibut (Anvifen, Fenibut, Noofen)
- Baclofen (Lioresal)
- Mirogabalin (Tarlige) (Japan Only)
Not approved:
- Imagabalin
- Tolibut
- 4-Flurophenibut
- HSK16149
- Trans-4 and cis-4-[18F] fluorogabapentin (α2δ PET Imaging)
- 4-Methylpregabalin
- PD-217,014
- Atagabalin
- Arbaclofen
- Saclofen
Opioids
Contrary to popular misconception, opioids are not depressants in the classical sense.[4] They do produce central nervous system depression, however, they also excite certain areas of the central nervous system. To remain true to the term 'depressant' – opioids cannot be classified as such. For opioid agonists and opium derivatives, these are classified differently. Analgesic or narcotic correctly identifies these drugs. However, they do have depressant actions nonetheless.
Piperidinediones
![](http://upload.wikimedia.org/wikipedia/commons/thumb/3/37/Glutethimide.svg/150px-Glutethimide.svg.png)
Piperidinediones are a class of depressants that are not used anymore. There are Piperidinediones that are used for other purposes like breast cancer.[1][2][3] . The Piperidinedione class is very structurally similar to barbiturates. Piperidinediones inclide Glutethimide, Methyprylon, Pyrithyldione, Glutarimide, and Aminoglutethimide. The first 3, (Glutethimide, Methyprylon, Pyrithyldione) are central nervous depressants. The Piperidinedione depressants, specifcally Glutethimide is a positive modulator of the GABAA anion channel. The drug increases inhibitory GABAergic tone and causes neuro-inhibition of the cortical and limbic systems, observed clinically as a sedative-hypnotic effect.[4] Glutethimide is also a potent inhibitor of the CYP 2D6 enzyme in the liver. This enzyme is responsible for converting many drugs from beta blockers to antidepressants to opioids and opiates. Due to its effects on the conversion of opioids, it was highly abused and mixed with opioids like codeine. Codeine needs to get metabolized to morphine in the liver to have its psychoactive and analgesic effects. Mixing codeine with the Piperidinedione Glutethimide allowed more codeine to be converted into morphine in the body; this increasing its effect. This was known as "hits", "cibas and codeine", "Dors and 4s". Glutethimide was believed to be safer than barbiturates, but many people died from the drug. Demand was high in the United States at one point. Production of glutethimide was discontinued in the US in 1993 and in several eastern European countries, most notably Hungary, in 2006.
Glutethimide withdrawal is intense and resembles barbiturate withdrawal. It features hallucinations and delirium; typical of a depressant withdrawal. In the 1970s, there were reports of neonatal withdrawal from glutethimide. Infants born to mothers addicted to glutethimide responded well initially, then had recurrence of symptoms about 5 days later, including overactivity, restlessness, tremors, hyperreflexia, hypotonus, vasomotor instability, incessant crying, and general irritability.
Glutethimide withdrawal featured severe agitation, tremor and seizures which could be fatal.
Overdose causes stupor or coma and respiratory depression.
- Methyprylon (Dimerin, Methyprylone, Noctan, Noludar)
- Pyrithyldione (Presidon, Pyridion, Pyridione, Pyrithyldion, Pyrithyldione)
- Piperidione (Ascron, Dihyprylon, Dihyprylone, Sedulon, Tusseval) (Withdrawan before approval)
- Glutethimide (Doriden)
Quinazolinone
Quinazolinones are a class of depressants that are rarely used anymore. Quinazolinone have powerful sedative, hypnotic, and anxiolytic effects. Quinazolinones structures are very similar to some antibiotics. Quinazolines main mechanism of action is binding to the GABAA receptor.[72] It does not bind to the ethanol, barbiturate, neurosteroid, or benzodiazepine site.[72] Instead it binds on a site right betwen the GABRB2 (β2) and (α1) GABRA1 proteins on the GABAA receptor.[72] The anesthetic etomidate and Anticonvulsant loreclezole may also bind to this site.[72]
Overdose on Quinazolinone sometimes causes effects that are the opposite of Quinazolinone like sedation. Overdose consists of hyperreflexia, vomiting, kidney failure, delirium, hypertonia, coma, myoclonic twitches, somnolence, euphoria, muscular hyperactivity, agitated delirium, tachycardia, and tonic-clonic seizures. In 1982 2,764 people visited US emergency rooms from overdosing on Quinazolinones, specifically Methaqualone.[73] Mixing Quinazolines with another depressant is possibly fatal. Death from a Quinazolinone overdose is usually caused by death through cardiac or respiratory arrest. Overdose resembles barbiturate/carbamate overdose.
Quinazolinones withdrawal occurs when someone has become dependent on a quinazolinone substance and stops using them. Quinazolinone withdrawal resembles ethanol, barbiturate, benzodiazepine and carbamate withdrawal. It usually consists of restlessness, nausea and vomiting, decreased appetite, tachycardia, insomnia, tremor, hallucinations, delirium, confusion, seizures; which could cause death, EEG photoparoxysmal response, myoclonic twitches, fever, muscle spasms, and irritability.[74]
Methaqualone hydrochloride, a Quinazolinone anxiolytic and hypnotic is referred to as "quaaludes" "ludes" and "disco biscuits". Methaqualone was very commonly abused in the western world during the 1960s and 1970s. Methaqualone was mainly prescribed for insomnia as it was thought to be safer than barbiturates and carbamates.[5] Methaqualone became highly abused by people and celebrities after it's introduction in 1965.[73] Methaqualone was first synthesized in India in 1951 by Indra Kishore Kacker and Syed Husain Zaheer, who were conducting research on finding new antimalarial medications.[75][76] The drug name "Quaalude" (Methaqualone) is a portmanteau, combining the words "quiet interlude". Methaqualone was discontinued in the United States in 1985, mainly due to its psychological addictiveness, widespread abuse, and illegal recreational use. Non-benzodiazepines, and benzodiazepines are now uses to treat insomnia instead. Methaqualone is now a schedule I substance. Some quinazolinone analogues are still sold online. They come with risks of seizures.
Large doses of Methaqualone cause euphoria, disinhibition, increased sexuality, sociability, muscle relaxation, anxiolysis, and sedation. Today Methaqualone is widely abused in South Africa. Many celebrities have used Quinazolinone; specifically Methaqualone. Bill Cosby admitted to casual sex involving recreational use of Methaqualone (Quaaludes).[77][78][79] 18 year old actor Anissa Jones died at 18 from an overdose of cocaine, PCP, Methaqualone, and the barbiturate Seconal. Billy Murcia a drummer for the rock band New York Dolls died at 21 when he drowned in a bathtub while overdosing on heroin and Methaqualone.[80]
Cloroqualone was a Quinazolinone that binded to the GABAA and sigma-1 receptor. It had useful cough suppressant effects and weaker sedative effects than Methaqualone. But it was withdrawan due to its potential for abuse and overdose.[81]
Diproqualone is a Quinazolinone that is still used today. Diproqualone has sedative, anxiolytic, antihistamine and analgesic properties, resulting from its agonist activity at the β subtype of the GABAa receptor, antagonist activity at all histamine receptors, inhibition of the cyclooxygenase-1 enzyme, and possibly its agonist activity at both the sigma-1 receptor and sigma-2 receptor. Diproqualone is used primarily for the treatment of inflammatory pain associated with osteoarthritis and rheumatoid arthritis, and more rarely for treating insomnia, anxiety and neuralgia. Diproqualone is the only analogue of methaqualone that is still in widespread clinical use, due to its useful anti-inflammatory and analgesic effects in addition to the sedative and anxiolytic actions common to other drugs of this class. There are still some concerns about the potential of diproqualone for abuse and overdose, and so it is not sold as a pure drug but only as the camphosulfonate salt in combination mixtures with other medicines such as ethenzamide.
Etaqualone is a quinazolinone-class depressant. It has sedative, hypnotic, muscle relaxant and central nervous system depressant properties. It was highly abused, and had high risk for overdose. Users would snort or smoke the free base Etaqualone hydrochloride salt.
Methylmethaqualone is an analogue of Methaqualone with similar hypnotic and sedative effects. Methylmethaqualone differs from methaqualone by 4-methylation on the phenyl ring. It produces convulsions at only slightly above the effective sedative dose.[82] It would appear that this compound was sold on the black market in Germany as a designer drug analogue of methaqualone.[83]
Nitromethaqualone is a quinazolinone depressant with 10x more powerful hypnotic and sedative effects than Methaqualone.[84]
Quinazolinone's:
- Alfoqualone (Arofuto)
- Cloroqualone
- Diproqualone
- Etaqualone (Aolan, Athinazone, Ethinazone)
- Mebroqualone (MBQ)
- Mecloqualone (Nubarene, Casfen)
- Methaqualone (Quaalude, Sopor, Mandrax)
- Methylmethaqualone
- Nitromethaqualone
- SL-164 (Dicloqualone, DCQ)
Miscellaneous
- Alpha and beta blockers (carvedilol, propranolol, atenolol, etc.)
- Anticholinergics (atropine, hyoscyamine, scopolamine, etc.)
- Anticonvulsants (topiramate, carbamazepine, lamotrigine, etc.)
- Antihistamines (diphenhydramine, doxylamine, promethazine, etc.)
- Antipsychotics (haloperidol, chlorpromazine, clozapine, etc.)
- Hypnotics (zolpidem, zopiclone, chloral hydrate, eszopiclone, etc.)
- Muscle relaxants (baclofen, phenibut, carisoprodol, cyclobenzaprine, etc.)
- Sedatives (gamma-hydroxybutyrate, etc.)
Methods of intake
Combining multiple depressants can be very dangerous because the central nervous system's depressive properties have been proposed to increase exponentially instead of linearly.[citation needed] This characteristic makes depressants a common choice for deliberate overdoses in the case of suicide. The use of alcohol or benzodiazepines along with the usual dose of heroin is often the cause of overdose deaths in opiate addicts.
See also
References
- ^ "Depressant – Definition". Princeton WordNet. Retrieved 28 December 2013.
- ^ "Minimum Legal Age Limits". IARD.org. International Alliance for Responsible Drinking. Archived from the original on 4 May 2016. Retrieved 23 June 2016.
- ^ Ethanol Level at eMedicine
- ^ a b World Health Organization (August 31, 2009). Clinical Guidelines for Withdrawal Management and Treatment of Drug Dependence in Closed Settings (PDF). p. 3. ISBN 978-92-9061-430-2. Archived from the original (PDF) on March 12, 2014.
Cannabis is a depressant drug, but it also has hallucinogenic effects.
- ^ Amsterdam, Jan; Nutt, David; Brink, Wim (January 23, 2013). "Generic legislation of new psychoactive drugs" (PDF). J Psychopharmacol. 27 (3): 317–324. doi:10.1177/0269881112474525. PMID 23343598. S2CID 12288500.
Figure 1
- ^ Hájos, N.; Katona, I.; Naiem, S. S.; Mackie, K.; Ledent, C.; Mody, I.; Freund, T. F. (2000). "Cannabinoids inhibit hippocampal GABAergic transmission and network oscillations". European Journal of Neuroscience. 12 (9): 3239–3249. doi:10.1046/j.1460-9568.2000.00217.x. PMID 10998107. S2CID 23141482.
- ^ Jordan, Allan M.; Khan, Tariq H.; Malkin, Hugh; Osborn, Helen M. I. (August 2002). "Synthesis and analysis of urea and carbamate prodrugs as candidates for melanocyte-directed enzyme prodrug therapy (MDEPT)". Bioorganic & Medicinal Chemistry. 10 (8): 2625–2633. doi:10.1016/s0968-0896(02)00097-4. ISSN 0968-0896. PMID 12057651.
- ^ a b c d Conermann, Till; Christian, Desirae (2022), "Carisoprodol", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID 31971718, retrieved 2022-11-30
- ^ Kulig, Katarzyna; Malawska, Barbara (October 2007). "Carisbamate, a new carbamate for the treatment of epilepsy". IDrugs: The Investigational Drugs Journal. 10 (10): 720–727. ISSN 1369-7056. PMID 17899491.
- ^ Kavelman, D. A.; Lewis, J. A. (1963-11-09). "Clinical Evaluation of a New Antihypertensive Agent: W583 (Mebutamate)". Canadian Medical Association Journal. 89 (19): 993–995. ISSN 0008-4409. PMC 1921904. PMID 14076168.
- ^ Rho, J. M.; Donevan, S. D.; Rogawski, M. A. (March 1997). "Barbiturate-like actions of the propanediol dicarbamates felbamate and meprobamate". The Journal of Pharmacology and Experimental Therapeutics. 280 (3): 1383–1391. ISSN 0022-3565. PMID 9067327.
- ^ "Meprobamate", LiverTox: Clinical and Research Information on Drug-Induced Liver Injury, Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases, 2012, PMID 31644030, retrieved 2022-11-30
- ^ Gonzalez, Lorie A.; Gatch, Michael B.; Taylor, Cynthia M.; Bell-Horner, Cathy L.; Forster, Michael J.; Dillon, Glenn H. (May 2009). "Carisoprodol-Mediated Modulation of GABAA Receptors: In Vitro and in Vivo Studies". The Journal of Pharmacology and Experimental Therapeutics. 329 (2): 827–837. doi:10.1124/jpet.109.151142. ISSN 0022-3565. PMC 2672873. PMID 19244096.
- ^ Twyman, Roy E.; Rogers, Carl J.; Macdonald, Robert L. (March 1989). "Differential regulation of ?-aminobutyric acid receptor channels by diazepam and phenobarbital". Annals of Neurology. 25 (3): 213–220. doi:10.1002/ana.410250302. hdl:2027.42/50330. ISSN 0364-5134. PMID 2471436. S2CID 72023197.
- ^ Twyman, R.; Rogers, C. J.; Macdonald, R. (1989). "Differential regulation of γ‐aminobutyric acid receptor channels by diazepam and phenobarbital". Annals of Neurology. 25 (3): 213–220. doi:10.1002/ANA.410250302. hdl:2027.42/50330. PMID 2471436. S2CID 72023197.
- ^ Ni, Karen; Cary, Margaret; Zarkowski, Paul (October 2007). "Carisoprodol withdrawal induced delirium: A case study". Neuropsychiatric Disease and Treatment. 3 (5): 679–682. ISSN 1176-6328. PMC 2656305. PMID 19300598.
- ^ Spencer, Sade; Brown, Robyn M.; Quintero, Gabriel C.; Kupchik, Yonatan M.; Thomas, Charles A.; Reissner, Kathryn J.; Kalivas, Peter W. (2014-06-18). "α2δ-1 signaling in nucleus accumbens is necessary for cocaine-induced relapse". The Journal of Neuroscience. 34 (25): 8605–8611. doi:10.1523/JNEUROSCI.1204-13.2014. ISSN 1529-2401. PMC 4061396. PMID 24948814.
- ^ Dooley DJ, Taylor CP, Donevan S, Feltner D (2007). "Ca2+ channel alpha2delta ligands: novel modulators of neurotransmission". Trends Pharmacol. Sci. 28 (2): 75–82. doi:10.1016/j.tips.2006.12.006. PMID 17222465.
- ^ a b Elaine Wyllie; Gregory D. Cascino; Barry E. Gidal; Howard P. Goodkin (17 February 2012). Wyllie's Treatment of Epilepsy: Principles and Practice. Lippincott Williams & Wilkins. p. 423. ISBN 978-1-4511-5348-4.
- ^ Honorio Benzon; James P. Rathmell; Christopher L. Wu; Dennis C. Turk; Charles E. Argoff; Robert W Hurley (11 September 2013). Practical Management of Pain. Elsevier Health Sciences. p. 1006. ISBN 978-0-323-17080-2.
- ^ Fernstrom, John D. (June 2005). "Branched-chain amino acids and brain function". The Journal of Nutrition. 135 (6 Suppl): 1539S–46S. doi:10.1093/jn/135.6.1539S. ISSN 0022-3166. PMID 15930466.
- ^ Sneader, Walter (2005-10-31). Drug Discovery: A History. John Wiley & Sons. ISBN 978-0-470-01552-0.
- ^ Levandovskiy, Igor A; Sharapa, Dmitry I; Shamota, Tatyana V; Rodionov, Vladimir N; Shubina, Tatyana E (2011-02-01). "Conformationally restricted GABA analogs: from rigid carbocycles to cage hydrocarbons". Future Medicinal Chemistry. 3 (2): 223–241. doi:10.4155/fmc.10.287. ISSN 1756-8919. PMID 21428817.
- ^ Bryans, Justin S.; Wustrow, David J. (1999). "3-Substituted GABA analogs with central nervous system activity: A review". Medicinal Research Reviews. 19 (2): 149–77. doi:10.1002/(SICI)1098-1128(199903)19:2<149::AID-MED3>3.0.CO;2-B. PMID 10189176. S2CID 38496241.
- ^ Uchitel, O. D; Di Guilmi, M. N.; Urbano, F. J.; Gonzalez-Inchauspe, C. (2010). "Acute modulation of calcium currents and synaptic transmission by gabapentinoids". Channels (Austin). 4 (6): 490–496. doi:10.4161/chan.4.6.12864. PMID 21150315.
- ^ Sills, G. J. (2006). "The mechanisms of action of gabapentin and pregabalin". Current Opinion in Pharmacology. 6 (1): 108–13. doi:10.1016/j.coph.2005.11.003. PMID 16376147.
- ^ Lapin, I. (2001). "Phenibut (beta-phenyl-GABA): a tranquilizer and nootropic drug". CNS Drug Reviews. 7 (4): 471–481. doi:10.1111/j.1527-3458.2001.tb00211.x. ISSN 1080-563X. PMC 6494145. PMID 11830761.
- ^ Abramets, I. I.; Komissarov, I. V. (June 1985). "[Effect of fenibut on the GABA B receptors of the spinal motor neurons]". Biulleten' Eksperimental'noi Biologii I Meditsiny. 99 (6): 698–700. ISSN 0365-9615. PMID 2861865.
- ^ "Gabapentin – an overview | ScienceDirect Topics". www.sciencedirect.com. Retrieved 2022-04-26.
- ^ "Target Information | Therapeutic Target Database". db.idrblab.net. Retrieved 2022-05-23.
- ^ Douglas Kirsch (10 October 2013). Sleep Medicine in Neurology. John Wiley & Sons. p. 241. ISBN 978-1-118-76417-6.
- ^ Frye, Mark; Moore, Katherine (2009). "Gabapentin and Pregabalin". In Schatzberg, Alan F.; Nemeroff, Charles B. (eds.). The American Psychiatric Publishing Textbook of Psychopharmacology. pp. 767–77. doi:10.1176/appi.books.9781585623860.as38. ISBN 978-1-58562-309-9.
- ^ Garcia-Borreguero, D.; Larrosa, O.; de la Llave, Y.; Verger, K.; Masramon, X.; Hernandez, G. (2002-11-26). "Treatment of restless legs syndrome with gabapentin: a double-blind, cross-over study". Neurology. 59 (10): 1573–1579. doi:10.1212/wnl.59.10.1573. ISSN 0028-3878. PMID 12451200. S2CID 45436475.
- ^ Derry, Sheena; Bell, Rae Frances; Straube, Sebastian; Wiffen, Philip J.; Aldington, Dominic; Moore, R. Andrew (2019-01-23). "Pregabalin for neuropathic pain in adults". The Cochrane Database of Systematic Reviews. 1 (1): CD007076. doi:10.1002/14651858.CD007076.pub3. ISSN 1469-493X. PMC 6353204. PMID 30673120.
- ^ Ryvlin, Philippe; Perucca, Emilio; Rheims, Sylvain (December 2008). "Pregabalin for the management of partial epilepsy". Neuropsychiatric Disease and Treatment. 4 (6): 1211–1224. doi:10.2147/ndt.s4716. ISSN 1176-6328. PMC 2646650. PMID 19337461.
{{cite journal}}
: CS1 maint: unflagged free DOI (link) - ^ Derry, Sheena; Cording, Malene; Wiffen, Philip J.; Law, Simon; Phillips, Tudor; Moore, R. Andrew (2016-09-29). "Pregabalin for pain in fibromyalgia in adults". The Cochrane Database of Systematic Reviews. 9 (5): CD011790. doi:10.1002/14651858.CD011790.pub2. ISSN 1469-493X. PMC 6457745. PMID 27684492.
- ^ Baldwin, David S; Ajel, Khalil; Masdrakis, Vasilios G; Nowak, Magda; Rafiq, Rizwan (2013). "Pregabalin for the treatment of generalized anxiety disorder: an update". Neuropsychiatric Disease and Treatment. 9: 883–892. doi:10.2147/NDT.S36453. ISSN 1176-6328. PMC 3699256. PMID 23836974.
{{cite journal}}
: CS1 maint: unflagged free DOI (link) - ^ Cappuzzo, Kimberly A (2009). "Treatment of postherpetic neuralgia: focus on pregabalin". Clinical Interventions in Aging. 4: 17–23. ISSN 1176-9092. PMC 2685221. PMID 19503762.
- ^ Lo, Hsiao-Sui; Yang, Chien-Ming; Lo, Helen G.; Lee, Chien-Ying; Ting, Hua; Tzang, Bor-Show (March 2010). "Treatment effects of gabapentin for primary insomnia". Clinical Neuropharmacology. 33 (2): 84–90. doi:10.1097/WNF.0b013e3181cda242. ISSN 1537-162X. PMID 20124884. S2CID 4046961.
- ^ Freynhagen, Rainer; Backonja, Miroslav; Schug, Stephan; Lyndon, Gavin; Parsons, Bruce; Watt, Stephen; Behar, Regina (2016). "Pregabalin for the Treatment of Drug and Alcohol Withdrawal Symptoms: A Comprehensive Review". CNS Drugs. 30 (12): 1191–1200. doi:10.1007/s40263-016-0390-z. ISSN 1172-7047. PMC 5124051. PMID 27848217.
- ^ Sood, Amit; Ebbert, Jon O.; Wyatt, Kirk D.; Croghan, Ivana T.; Schroeder, Darrell R.; Sood, Richa; Hays, J. Taylor (March 2010). "Gabapentin for smoking cessation". Nicotine & Tobacco Research. 12 (3): 300–304. doi:10.1093/ntr/ntp195. ISSN 1462-2203. PMC 2825098. PMID 20081039.
- ^ Kawalec, Paweł; Cierniak, Agnieszka; Pilc, Andrzej; Nowak, Gabriel (April 2015). "Pregabalin for the treatment of social anxiety disorder". Expert Opinion on Investigational Drugs. 24 (4): 585–594. doi:10.1517/13543784.2014.979283. ISSN 1744-7658. PMID 25361817. S2CID 207477337.
- ^ Sokolski, K. N.; Green, C.; Maris, D. E.; DeMet, E. M. (December 1999). "Gabapentin as an adjunct to standard mood stabilizers in outpatients with mixed bipolar symptomatology". Annals of Clinical Psychiatry. 11 (4): 217–222. doi:10.1023/a:1022361412956. ISSN 1040-1237. PMID 10596736. S2CID 8468706.
- ^ Conesa, María‐Llanos; Rojo, Luis‐Miguel; Plumed, Javier; Livianos, Lorenzo (2012-01-16). "Pregabalin in the Treatment of Refractory Bipolar Disorders". CNS Neuroscience & Therapeutics. 18 (3): 269–270. doi:10.1111/j.1755-5949.2011.00289.x. ISSN 1755-5930. PMC 6493626. PMID 22449111.
- ^ Hamrin, V.; Bailey, K. (2001). "Gabapentin and methylphenidate treatment of a preadolescent with attention deficit hyperactivity disorder and bipolar disorder". Journal of Child and Adolescent Psychopharmacology. 11 (3): 301–309. doi:10.1089/10445460152595630. ISSN 1044-5463. PMID 11642481.
- ^ Pandya, K J; Morrow, G R; Roscoe, J A; Hickok, J T; Zhao, H; Pajon, E; Sweeney, T J; Banerjee, T K; Flynn, P J (2005-09-03). "Gabapentin for hot flashes in 420 women with breast cancer: a randomised double-blind placebo-controlled trial". Lancet. 366 (9488): 818–824. doi:10.1016/S0140-6736(05)67215-7. ISSN 0140-6736. PMC 1627210. PMID 16139656.
- ^ "Baclofen". The American Society of Health-System Pharmacists. Retrieved 2011-12-06.
- ^ a b Lapin I (2001). "Phenibut (beta-phenyl-GABA): a tranquilizer and nootropic drug". CNS Drug Reviews. 7 (4): 471–81. doi:10.1111/j.1527-3458.2001.tb00211.x. PMC 6494145. PMID 11830761.
- ^ Hägg, Staffan; Jönsson, Anna K.; Ahlner, Johan (2020). "Current Evidence on Abuse and Misuse of Gabapentinoids". Drug Safety. 43 (12): 1235–1254. doi:10.1007/s40264-020-00985-6. ISSN 0114-5916. PMC 7686181. PMID 32857333.
- ^ Smith, Blair H; Higgins, Cassie; Baldacchino, Alex; Kidd, Brian; Bannister, Jonathan (August 2012). "Substance misuse of gabapentin". The British Journal of General Practice. 62 (601): 406–407. doi:10.3399/bjgp12X653516. ISSN 0960-1643. PMC 3404313. PMID 22867659.
- ^ Althobaiti, Yusuf S.; Alghorabi, Amal; Alshehri, Fahad S.; Baothman, Bandar; Almalki, Atiah H.; Alsaab, Hashem O.; Alsanie, Walaa; Gaber, Ahmed; Almalki, Hussam; Alghamdi, Abdulrahman S.; Basfer, Ahmad (2020-06-26). "Gabapentin-induced drug-seeking-like behavior: a potential role for the dopaminergic system". Scientific Reports. 10 (1): 10445. Bibcode:2020NatSR..1010445A. doi:10.1038/s41598-020-67318-6. ISSN 2045-2322. PMC 7320158. PMID 32591630.
- ^ "FDA warns about serious breathing problems with seizure and nerve pain medicines gabapentin (Neurontin, Gralise, Horizant) and pregabalin (Lyrica, Lyrica CR)". U.S. Food and Drug Administration (FDA). 19 December 2019. Archived from the original on 22 December 2019. Retrieved 21 December 2019.
This article incorporates text from this source, which is in the public domain.
- ^ Gomes, Tara; Juurlink, David N.; Antoniou, Tony; Mamdani, Muhammad M.; Paterson, J. Michael; van den Brink, Wim (2017-10-03). "Gabapentin, opioids, and the risk of opioid-related death: A population-based nested case–control study". PLOS Medicine. 14 (10): e1002396. doi:10.1371/journal.pmed.1002396. ISSN 1549-1277. PMC 5626029. PMID 28972983.
{{cite journal}}
: CS1 maint: unflagged free DOI (link) - ^ Kriikku, Pirkko; Ojanperä, Ilkka (July 2021). "Pregabalin and gabapentin in non-opioid poisoning deaths". Forensic Science International. 324: 110830. doi:10.1016/j.forsciint.2021.110830. ISSN 1872-6283. PMID 34000615. S2CID 234770186.
- ^ Elliott, Simon P.; Burke, Timothy; Smith, Christopher (January 2017). "Determining the Toxicological Significance of Pregabalin in Fatalities". Journal of Forensic Sciences. 62 (1): 169–173. doi:10.1111/1556-4029.13263. ISSN 1556-4029. PMID 27864947. S2CID 39480384.
- ^ Kalk, Nicola J.; Chiu, Ching-Ting; Sadoughi, Rasa; Baho, Heli; Williams, Bryn D.; Taylor, David; Copeland, Caroline S. (2022-04-18). "Fatalities associated with gabapentinoids in England (2004–2020)". British Journal of Clinical Pharmacology. 88 (8): 3911–3917. doi:10.1111/bcp.15352. ISSN 1365-2125. PMC 9543893. PMID 35435281. S2CID 248228229.
- ^ Gabapentin for Adults with Neuropathic Pain: A Review of the Clinical Efficacy and Safety. CADTH Rapid Response Reports. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health. 2015. PMID 26180879.
- ^ Toth, Cory (February 2014). "Pregabalin: latest safety evidence and clinical implications for the management of neuropathic pain". Therapeutic Advances in Drug Safety. 5 (1): 38–56. doi:10.1177/2042098613505614. ISSN 2042-0986. PMC 4110876. PMID 25083261.
- ^ Desai, Aaron; Kherallah, Yazan; Szabo, Cheryl; Marawar, Rohit (March 2019). "Gabapentin or pregabalin induced myoclonus: A case series and literature review". Journal of Clinical Neuroscience. 61: 225–234. doi:10.1016/j.jocn.2018.09.019. ISSN 1532-2653. PMID 30381161. S2CID 53165515.
- ^ Isoardi, Katherine Z.; Polkinghorne, Gregory; Harris, Keith; Isbister, Geoffrey K. (December 2020). "Pregabalin poisoning and rising recreational use: a retrospective observational series". British Journal of Clinical Pharmacology. 86 (12): 2435–2440. doi:10.1111/bcp.14348. ISSN 1365-2125. PMC 7688538. PMID 32374500.
- ^ Gibbons, Robert D.; Hur, Kwan; Brown, C. Hendricks; Mann, J. John (December 2010). "Gabapentin and Suicide Attempts". Pharmacoepidemiology and Drug Safety. 19 (12): 1241–1247. doi:10.1002/pds.2036. ISSN 1053-8569. PMC 2992093. PMID 20922708.
- ^ Cross, Aaron L.; Viswanath, Omar; Sherman, Andrew l (2022), "Pregabalin", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID 29261857, retrieved 2022-05-21
- ^ Read, Stephanie H.; Giannakeas, Vasily; Pop, Paula; Bronskill, Susan E.; Herrmann, Nathan; Chen, Simon; Luke, Miles J.; Wu, Wei; McCarthy, Lisa M.; Austin, Peter C.; Normand, Sharon-Lise (October 2021). "Evidence of a gabapentinoid and diuretic prescribing cascade among older adults with lower back pain". Journal of the American Geriatrics Society. 69 (10): 2842–2850. doi:10.1111/jgs.17312. ISSN 1532-5415. PMID 34118076. S2CID 235412378.
- ^ Quintero, Gabriel C (2017-02-09). "Review about gabapentin misuse, interactions, contraindications and side effects". Journal of Experimental Pharmacology. 9: 13–21. doi:10.2147/JEP.S124391. ISSN 1179-1454. PMC 5308580. PMID 28223849.
{{cite journal}}
: CS1 maint: unflagged free DOI (link) - ^ "Pregabalin Use During Pregnancy". Drugs.com. Retrieved 2022-06-11.
- ^ Schifano, Fabrizio (2014-06-01). "Misuse and Abuse of Pregabalin and Gabapentin: Cause for Concern?". CNS Drugs. 28 (6): 491–496. doi:10.1007/s40263-014-0164-4. ISSN 1179-1934. PMID 24760436. S2CID 4508086.
- ^ Ishikawa, Hayahito; Takeshima, Masahiro; Ishikawa, Hiroyasu; Ayabe, Naoko; Ohta, Hidenobu; Mishima, Kazuo (September 2021). "Pregabalin withdrawal in patients without psychiatric disorders taking a regular dose of pregabalin: A case series and literature review". Neuropsychopharmacology Reports. 41 (3): 434–439. doi:10.1002/npr2.12195. ISSN 2574-173X. PMC 8411313. PMID 34382380.
- ^ Hellwig, Thaddaus R.; Hammerquist, Rhonda; Termaat, Jill (2010-06-01). "Withdrawal symptoms after gabapentin discontinuation". American Journal of Health-System Pharmacy. 67 (11): 910–912. doi:10.2146/ajhp090313. ISSN 1535-2900. PMID 20484214.
- ^ Alvis, Bret D.; Sobey, Christopher M. (January 2017). "Oral Baclofen Withdrawal Resulting in Progressive Weakness and Sedation Requiring Intensive Care Admission". The Neurohospitalist. 7 (1): 39–40. doi:10.1177/1941874416637404. ISSN 1941-8744. PMC 5167087. PMID 28042369.
- ^ a b Hardman, Matthew I.; Sprung, Juraj; Weingarten, Toby N. (May 2019). "Acute phenibut withdrawal: A comprehensive literature review and illustrative case report". Bosnian Journal of Basic Medical Sciences. 19 (2): 125–129. doi:10.17305/bjbms.2018.4008. ISSN 1512-8601. PMC 6535394. PMID 30501608.
- ^ Mohammed, Imran; Hussain, Asif (2004-08-09). "Intrathecal baclofen withdrawal syndrome- a life-threatening complication of baclofen pump: A case report". BMC Clinical Pharmacology. 4: 6. doi:10.1186/1472-6904-4-6. ISSN 1472-6904. PMC 514562. PMID 15301690.
{{cite journal}}
: CS1 maint: unflagged free DOI (link) - ^ a b c d Hammer, Harriet; Bader, Benjamin M.; Ehnert, Corina; Bundgaard, Christoffer; Bunch, Lennart; Hoestgaard-Jensen, Kirsten; Schroeder, Olaf H.-U.; Bastlund, Jesper F.; Gramowski-Voß, Alexandra; Jensen, Anders A. (August 2015). "A Multifaceted GABAA Receptor Modulator: Functional Properties and Mechanism of Action of the Sedative-Hypnotic and Recreational Drug Methaqualone (Quaalude)". Molecular Pharmacology. 88 (2): 401–420. doi:10.1124/mol.115.099291. ISSN 0026-895X. PMC 4518083. PMID 26056160.
- ^ a b "Methaqualone (Encyclopedia of Drugs and Addictive Substances) - eNotes.com". 2012-02-23. Archived from the original on 2012-02-23. Retrieved 2022-12-01.
- ^ "Quaaludes Addiction and Abuse, Statistics, Signs, Symptoms & Side Effects". Addiction Hope. Retrieved 2022-12-01.
- ^ "Lawrence Journal-World - Google News Archive Search". news.google.com. Retrieved 2022-12-01.
- ^ van Zyl, Etienne F. (2001-11-01). "A survey of reported synthesis of methaqualone and some positional and structural isomers". Forensic Science International. 122 (2): 142–149. doi:10.1016/S0379-0738(01)00484-4. ISSN 0379-0738. PMID 11672968.
- ^ Moghe, Sonia (2015-07-25). "Cosby deposition: Quaaludes came from L.A. gynecologist". CNN. Retrieved 2022-12-01.
- ^ Bowley, Graham; Ember, Sydney (2015-07-19). "Bill Cosby, in Deposition, Said Drugs and Fame Helped Him Seduce Women". The New York Times. ISSN 0362-4331. Retrieved 2022-12-01.
- ^ "Gloria Allred wins Cobb Energy Bill Cosby concert protest case | Radio & TV Talk". 2016-09-11. Archived from the original on 2016-09-11. Retrieved 2022-12-01.
- ^ "New York Doll Murcia died here". shadyoldlady.com. Retrieved 2022-12-01.
- ^ PubChem. "Cloroqualone". pubchem.ncbi.nlm.nih.gov. Retrieved 2022-12-01.
- ^ "Wayback Machine" (PDF). 2011-07-19. Archived from the original (PDF) on 2011-07-19. Retrieved 2022-12-01.
- ^ "Wayback Machine" (PDF). 2011-07-19. Archived from the original (PDF) on 2011-07-19. Retrieved 2022-12-01.
- ^ Szirmai, A. (November 1963). "Pharmacological and Therapeutic Studies with a New Quinazolone Derivative, Nitromethaqualone". Therapeutische Umschau. Revue Therapeutique. 20: 542–546. ISSN 0040-5930. PMID 14101319.
External links
- Painfully Obvious – A Community Resource
- Fact sheets and Harm Reduction Strategies About Depressants and Other Recreational Drugs
- U.S. Department of Human and Health Services: Drug Categories for Substances of Abuse
- About Psychotropic Medications: Quick Reference to Medications Used in Mental Health Archived 2019-07-01 at the Wayback Machine
- National Institute on Drug Abuse: "NIDA for Teens: Prescription Depressant Medications".