Nicotine

From Wikipedia, the free encyclopedia

This is an old revision of this page, as edited by 138.38.156.20 (talk) at 09:30, 11 September 2009. The present address (URL) is a permanent link to this revision, which may differ significantly from the current revision.

This article is about the chemical compound. For other uses, see Nicotine (disambiguation).
Nicotine
Clinical data
Dependence
liability		Medium to high
Routes of
administration		smoked (as smoking tobacco, mapacho, etc.), insufflated (as tobacco snuff or nicotine nasal spray), chewed (as nicotine gum, tobacco gum or chewing tobacco), transdermal (as nicotine patch, nicogel or topical tobacco paste), intrabuccal (as dipping tobacco, snus, dissolvable tobacco or creamy snuff), injected (as NicVAX), vaporized (as electronic cigarette, etc.), directly inhaled (as nicotine inhaler), drank (as nicotini or NicLite)
ATC code
Legal status
Legal status
  • AU: Unscheduled
  • UK: Unscheduled
  • US: WARNING[1]Unscheduled, but age restricted.
Pharmacokinetic data
Bioavailability20 to 45% (oral)
Elimination half-life2 hours
Identifiers
  • 3-[(2S)-1-methylpyrrolidin-2-yl]pyridine
CAS Number
PubChem CID
ChemSpider
CompTox Dashboard (EPA)
ECHA InfoCard100.000.177 Edit this at Wikidata
Chemical and physical data
FormulaC10H14N2
Molar mass162.26 g/mol g·mol−1
3D model (JSmol)
Density1.01 g/cm3
Melting point−79 °C (−110 °F)
Boiling point247 °C (477 °F)
  • C1=CC=NC=C1[C@@H]2CCCN2C
  (verify)

Nicotine is an alkaloid found in the nightshade family of plants (Solanaceae) which constitutes approximately 0.6–3.0% of dry weight of tobacco,[2][3] with biosynthesis taking place in the roots, and accumulating in the leaves. It functions as an antiherbivore chemical with particular specificity to insects; therefore nicotine was widely used as an insecticide in the past,[4][5] and currently nicotine analogs such as imidacloprid continue to be widely used.

In low concentrations (an average cigarette yields about 1 mg of absorbed nicotine), the substance acts as a stimulant in mammals and is the main factor responsible for the dependence-forming properties of tobacco smoking. According to the American Heart Association, the "nicotine addiction has historically been one of the hardest addictions to break." The pharmacological and behavioral characteristics that determine tobacco addiction are similar to those that determine addiction to drugs such as heroin and cocaine.[6] Nicotine content in cigarettes has actually slowly increased over the years, and one study found that there was an average increase of 1.6% per year between the years of 1998 and 2005. This was found for all major market categories of cigarettes.[7]

History and name

Nicotine is named after the tobacco plant Nicotiana tabacum, which in turn is named after Jean Nicot de Villemain, French ambassador in Portugal, who sent tobacco and seeds from Brazil to Paris in 1560 and promoted their medicinal use. Nicotine was first isolated from the tobacco plant in 1828 by German chemists Posselt & Reimann, who considered it a poison.[8] Its chemical empirical formula was described by Melsens in 1843,[9] its structure was discovered by Garry Pinner in 1893, and it was first synthesized by A. Pictet and Crepieux in 1904.[10]

Chemistry

Nicotine is a hygroscopic, oily liquid that is miscible with water in its base form. As a nitrogenous base, nicotine forms salts with acids that are usually solid and water soluble. Nicotine easily penetrates the skin. As shown by the physical data, free base nicotine will burn at a temperature below its boiling point, and its vapors will combust at 308 K (35 °C; 95 °F) in air despite a low vapor pressure. Because of this, most of the nicotine is burned when a cigarette is smoked; however, enough is inhaled to provide the desired effects. The amount of nicotine inhaled with tobacco smoke is a fraction of the amount contained in the tobacco leaves.

Optical activity

Nicotine is optically active, having two enantiomeric forms. The naturally-occurring form of nicotine is levorotatory, with [α]D = –166.4 °. The dextrorotatory form, (+)-nicotine, has only one-half the physiological activity of (–)-nicotine. It is therefore weaker in the sense that a higher dose is required to attain the same effects.[11] The salts of the (+)-nicotine are usually dextrorotatory.

Pharmacology

Pharmacokinetics

As nicotine enters the body, it is distributed quickly through the bloodstream and can cross the blood-brain barrier. On average it takes about seven seconds for the substance to reach the brain when inhaled[citation needed]. The half life of nicotine in the body is around two hours.[12]

The amount of nicotine absorbed by the body from smoking depends on many factors, including the type of tobacco, whether the smoke is inhaled, and whether a filter is used. For chewing tobacco, dipping tobacco, snus and snuff, which are held in the mouth between the lip and gum, or taken in the nose, the amount released into the body tends to be much greater than smoked tobacco. Nicotine is metabolized in the liver by cytochrome P450 enzymes (mostly CYP2A6, and also by CYP2B6). A major metabolite is cotinine.

Other primary metabolites include nicotine N'-oxide, nornicotine, nicotine isomethonium ion, 2-hydroxynicotine and nicotine glucuronide.[13]

Gluconuration and oxidative metabolism of nicotine to cotinine are both inhibited by menthol, an additive to mentholated cigarettes, thus increasing the half-life of nicotine in vivo[14].

Pharmacodynamics

Nicotine acts on the nicotinic acetylcholine receptors, specifically the ganglion type nicotinic receptor and one CNS nicotinic receptor. The former is present in the adrenal medulla and elsewhere, while the latter is present in the central nervous system (CNS). In small concentrations, nicotine increases the activity of these receptors. Nicotine also has effects on a variety of other neurotransmitters through less direct mechanisms.

In CNS

By binding to nicotinic acetylcholine receptors, nicotine increases the levels of several neurotransmitters - acting as a sort of "volume control". It is thought that increased levels of dopamine in the reward circuits of the brain are responsible for the euphoria and relaxation and eventual addiction caused by nicotine consumption. A single amino-acid difference between brain and muscle acetylcholine receptors explains why nicotine activates the CNS but does not activate skeletal muscles and cause instant death. Nicotine addiction is therefore a biological oddity. [15]

Tobacco smoke contains the monoamine oxidase inhibitors harman, norharman[16], anabasine, anatabine, and nornicotine. These compounds significantly decrease MAO activity in smokers.[16][17] MAO enzymes break down monoaminergic neurotransmitters such as dopamine, norepinephrine, and serotonin.

Chronic nicotine exposure via tobacco smoking up-regulates alpha4beta2* nAChR in cerebellum and brainstem regions[18][19] but not habenulopeduncular structures[20]. Alpha4beta2 and alpha6beta2 receptors, present in the ventral tegmental area, play a crucial role in mediating the reinforcement effects of nicotine.[21].

In PNS

Nicotine also activates the sympathetic nervous system,[22] acting via splanchnic nerves to the adrenal medulla, stimulates the release of epinephrine. Acetylcholine released by preganglionic sympathetic fibers of these nerves acts on nicotinic acetylcholine receptors, causing the release of epinephrine (and norepinephrine) into the bloodstream. Nicotine also has an affinity for melanin-containing tissues due to its precursor function in melanin synthesis or its irreversible binding of melanin and nicotine. This has been suggested to underlie the increased nicotine dependence and lower smoking cessation rates in darker pigmented individuals.[23]

In adrenal medulla

By binding to ganglion type nicotinic receptors in the adrenal medulla nicotine increases flow of adrenaline (epinephrine), a stimulating hormone. By binding to the receptors, it causes cell depolarization and an influx of calcium through voltage-gated calcium channels. Calcium triggers the exocytosis of chromaffin granules and thus the release of epinephrine (and norepinephrine) into the bloodstream. The release of epinephrine (adrenaline) causes an increase in heart rate, blood pressure and respiration, as well as higher blood glucose levels[24]

Cotinine is a byproduct of the metabolism of nicotine which remains in the blood for up to 48 hours. It can therefore be used as an indicator of a person's exposure to nicotine.[citation needed]

Psychoactive effects

Nicotine's mood-altering effects are different by report: in particular it is both a stimulant and a relaxant.[25] First causing a release of glucose from the liver and epinephrine (adrenaline) from the adrenal medulla, it causes stimulation. Users report feelings of relaxation, sharpness, calmness, and alertness.[26] By reducing the appetite and raising the metabolism, some smokers may lose weight as a consequence.[27][28]

When a cigarette is smoked, nicotine-rich blood passes from the lungs to the brain within seven seconds and immediately stimulates the release of many chemical messengers including acetylcholine, norepinephrine, epinephrine, vasopressin, arginine, dopamine, autocrine agents, and beta-endorphin.[29] This release of neurotransmitters and hormones is responsible for most of nicotine's effects. Nicotine appears to enhance concentration[30] and memory due to the increase of acetylcholine. It also appears to enhance alertness due to the increases of acetylcholine and norepinephrine. Arousal is increased by the increase of norepinephrine. Pain is reduced by the increases of acetylcholine and beta-endorphin. Anxiety is reduced by the increase of beta-endorphin. Nicotine also extends the duration of positive effects of dopamine[31] and increases sensitivity in brain reward systems.[32] Most cigarettes (in the smoke inhaled) contain 0.1 to 2.8 milligrams of nicotine.[33]

Research suggests that, when smokers wish to achieve a stimulating effect, they take short quick puffs, which produce a low level of blood nicotine.[34] This stimulates nerve transmission. When they wish to relax, they take deep puffs, which produce a high level of blood nicotine, which depresses the passage of nerve impulses, producing a mild sedative effect. At low doses, nicotine potently enhances the actions of norepinephrine and dopamine in the brain, causing a drug effect typical of those of psychostimulants. At higher doses, nicotine enhances the effect of serotonin and opiate activity, producing a calming, pain-killing effect. Nicotine is unique in comparison to most drugs, as its profile changes from stimulant to sedative/pain killer in increasing dosages and use.

Technically, nicotine is not significantly addictive, as nicotine administered alone does not produce significant reinforcing properties.[35] However, only after coadministration with an MAOI, such as those found in tobacco, nicotine produces significant behavioral sensitization, a measure of addiction potential. This is similar in effect to amphetamine.[36]

A 21 mg patch applied to the left arm

Nicotine gum, usually in 2-mg or 4-mg doses, and nicotine patches are available, as well as smokeless tobacco which do not have all the other ingredients in smoked tobacco.

Dependence

See also: Smoking cessation

Modern research shows that nicotine acts on the brain to produce a number of effects. Specifically, its addictive nature has been found to show that nicotine activates reward pathways—the circuitry within the brain that regulates feelings of pleasure and euphoria.[37]

Dopamine is one of the key neurotransmitters actively involved in the brain. Research shows that by increasing the levels of dopamine within the reward circuits in the brain, nicotine acts as a chemical with intense addictive qualities. In many studies it has been shown to be more addictive than cocaine and heroin, though chronic treatment has an opposite effect on reward thresholds.[citation needed] Like other physically addictive drugs, nicotine causes down-regulation of the production of dopamine and other stimulatory neurotransmitters as the brain attempts to compensate for artificial stimulation. In addition, the sensitivity of nicotinic acetylcholine receptors decreases. To compensate for this compensatory mechanism, the brain in turn upregulates the number of receptors, convoluting its regulatory effects with compensatory mechanisms meant to counteract other compensatory mechanisms. The net effect is an increase in reward pathway sensitivity, opposite of other drugs of abuse such as cocaine and heroin, which reduce reward pathway sensitivity.[32] This neuronal brain alteration persists for months after administration ceases. Due to an increase in reward pathway sensitivity, nicotine withdrawal is relatively mild compared to alcohol or heroin withdrawal.[citation needed] Nicotine also has the potential to cause dependence in many animals other than humans. Mice have been administered nicotine and exhibit withdrawal reactions when its administration is stopped.[citation needed]

A study found that nicotine exposure in adolescent mice retards the growth of the dopamine system, thus increasing the risk of substance abuse during adolescence.[38]

As the dopamine hypothesis of reward is slowly being challenged (ie, other systems may have a more vital role in reward), the conclusions drawn regarding the addictive nature of nicotine are likely to be troubled. If indeed, one of the more than 3000 uncharacterised chemicals in tobacco smoke activates one of the other pathways then there is the possibility that scientists will have to acknowledge, eventually, that nicotine is indeed not the primary reason for tobacco addiction and plays a minor role. Many studies that have employed nicotine in animal research (that has formed the basis for the addictive nature of nicotine) have utilised a method where an animal presses a lever to receive nicotine, but the amount of nicotine is often much higher than that received by a puff of a cigarette, even higher than all of the puffs in two cigarettes at once, leading to invalid conclusions. The new decade ahead my well produce controversial but necessary debate on the true nature of nicotine as an addictive substance.

Toxicology

See also: Nicotine poisoning

The LD50 of nicotine is 50 mg/kg for rats and 3 mg/kg for mice. 40–60 mg (0.5-1.0 mg/kg) can be a lethal dosage for adult humans.[39][40] Nicotine therefore has a high toxicity in comparison to many other alkaloids such as cocaine, which has an LD50 of 95.1 mg/kg when administered to mice. It is impossible however to overdose on nicotine through smoking alone (though a person can overdose on nicotine through a combination of nicotine patches, nicotine gum, and/or tobacco smoking at the same time.) [41][42] Spilling an extremely high concentration of nicotine onto the skin can result in intoxication or even death since nicotine readily passes into the bloodstream from dermal contact.[43]

The carcinogenic properties of nicotine in standalone form, separate from tobacco smoke, have not been evaluated by the IARC, and it has not been assigned to an official carcinogen group. The currently available literature indicates that nicotine, on its own, does not promote the development of cancer in healthy tissue and has no mutagenic properties. However, nicotine and the increased cholinergic activity it causes have been shown to impede apoptosis, which is one of the methods by which the body destroys unwanted cells (programmed cell death). Since apoptosis helps to remove mutated or damaged cells that may eventually become cancerous, the inhibitory actions of nicotine may create a more favourable environment for cancer to develop, though this also remains to be proven.[44][unreliable source?]

The teratogenic properties of nicotine have not yet been adequately researched, and while the likelihood of birth defects caused by nicotine is believed to be very small or nonexistent, nicotine replacement product manufacturers recommend consultation with a physician before using a nicotine patch or nicotine gum while pregnant or nursing.[44][unreliable source?]


Women who use nicotine gum and patches during the early stages of pregnancy face an increased risk of having babies with birth defects, says a study that looked at about 77,000 pregnant women in Denmark. The study found that women who use nicotine-replacement therapy in the first 12 weeks of pregnancy have a 60 percent greater risk of having babies with birth defects, compared to women who are non-smokers, the Daily Mail reported. The findings were published in the journal Obstetrics and Gynaecology.

Nicotine and oxidative stress

Nicotine is detoxified by the cytochrome p450 in the liver.

Link to circulatory disease

Nicotine has very powerful effects on arteries throughout the body. Nicotine is a stimulant, it raises blood pressure, and is a vasoconstrictor, making it harder for the heart to pump through the constricted arteries. It causes the body to release its stores of fat and cholesterol into the blood.[citation needed]

Nicotine has been speculated[who?] to increase the risk of blood clots by increasing plasminogen activator inhibitor-1, though this has not been proven. Plasma fibrinogen levels are elevated in smokers and are further elevated during acute COPD exacerbation. Also, Factor XIII, which stabilizes fibrin clots, is increased in smokers. But neither of the two previous effects have been shown yet to be caused by nicotine, [2] If blood clots in an artery, blood flow is reduced or halted, and tissue loses its source of oxygen and nutrients and dies in minutes.

Peripheral circulation, arteries going to the extremities, are also highly susceptible to the vasoconstrictor effects of nicotine as well as the increased risk of clots and clogging.[citation needed]

Therapeutic uses

The primary therapeutic use of nicotine is in treating nicotine dependence in order to eliminate smoking with its risks to health. Controlled levels of nicotine are given to patients through gums, dermal patches, lozenges, electronic/substitute cigarettes or nasal sprays in an effort to wean them off their dependence.

However, in a few situations, smoking has been observed to apparently be of therapeutic value to patients. These are often referred to as "Smoker’s Paradoxes".[45] Although in most cases the actual mechanism is understood only poorly or not at all, it is generally believed that the principal beneficial action is due to the nicotine administered, and that administration of nicotine without smoking may be as beneficial as smoking, without the higher risk to health due to tar and other ingredients found in tobacco.

For instance, recent studies suggest that smokers require less frequent repeated revascularization after percutaneous coronary intervention (PCI).[45] Risk of ulcerative colitis has been frequently shown to be reduced by smokers on a dose-dependent basis; the effect is eliminated if the individual stops smoking.[46][47] Smoking also appears to interfere with development of Kaposi's sarcoma,[48] breast cancer among women carrying the very high risk BRCA gene,[49] preeclampsia,[50] and atopic disorders such as allergic asthma.[51] A plausible mechanism of action in these cases may be nicotine acting as an anti-inflammatory agent, and interfering with the inflammation-related disease process, as nicotine has vasoconstrictive effects.[52]

With regard to neurological diseases, evidence suggests that the risk of developing Parkinson's disease or Alzheimer's disease might be 50% lower in smokers, compared to non-smokers.[53] Tobacco smoke has been shown to contain compounds capable of inhibiting MAO. Monoamine oxidase is responsible for the degredation of dopamine in the human brain. When dopamine is broken down by MAO-B, neurotoxic by-products are formed, possibly contributing to Parkinson's and Alzheimers disease.[54] Many such papers regarding Alzheimer's disease[55] and Parkinson's Disease[56] have been published. More recent studies find that there's no beneficial link between smoking and Alzheimer's, and in some cases suggest that it actually results in an earlier onset of the disease.[57][58][59][60]

Recent studies have indicated that nicotine can be used to help adults suffering from Autosomal dominant nocturnal frontal lobe epilepsy. The same areas that cause seizures in that form of epilepsy are also responsible for processing nicotine in the brain.[61]

It has been noted that the majority of people diagnosed with schizophrenia smoke tobacco. Estimates for the number of schizophrenics that smoke range from 75% to 90%. It was recently argued that the increased level of smoking in schizophrenia may be due to a desire to self-medicate with nicotine.[62][63] More recent research has found that mildly-dependent users got some benefit from nicotine, but not those who were highly-dependent.[64] All of these studies are based only on observation, and no interventional (randomized) studies have been done. Research on nicotine as administered through a patch or gum is ongoing.

Research as a potential basis for an antipsychotic agent

However, when the metabolites of nicotine were isolated and their effect on first the animal brain and then the human brain in people with schizophrenia were studied, it was shown that the effects helped with cognitive and negative symptoms of schizophrenia. Therefore, the nicotinergic agents, as antipsychotics which do not contain nicotine but act on the same receptors in the brain are showing promise as adjunct antipsychotics in early stages of FDA studies on schizophrenia. "The prepulse inhibition (PPI) is a phenomenon in which a weak prepulse attenuates the response to a subsequent startling stimulus. Therefore, PPI is believed to have face, construct, and predictive validity for the PPI disruption in schizophrenia, and it is widely used as a model to study the neurobiology of this disorder and for screening antipsychotics. Alpha7 nicotinic receptor agonists have reported to reverse the PPI disruption." Department of Clinical Pharmacology and Pharmacy, Neuroscience, Ehime University Graduate School of Medicine, Shitsukawa, Toon 791-0295, Japan.

Additionally, studies have shown that there are genes predisposing people with schizophrenia to nicotine use. "Evidence of association between smoking and alpha7 nicotinic receptor subunit gene in schizophrenia patients" .De Luca V, Wong AH, Muller DJ, Wong GW, Tyndale RF, Kennedy JL. Neurogenetics Section, Clarke Site, Centre for Addiction and Mental Health, Department of Psychiatry, Toronto, Ontario, Canada.

Therefore with these factors taken together the heavy usage of cigarettes and other nicotine related products among people with schizophrenia may be explained and novel antipsychotic agents developed that have these effects in a manner that is not harmful and controlled and is a promising arena of research for schizophrenia.

Nicotine and its metabolites are being researched for the treatment of a number of disorders, including ADHD, Schizophrenia and Parkinson's Disease.[65]

The therapeutic use of nicotine as a means of appetite-control and to promote weight loss is anecdotally supported by many ex-smokers who claim to put on weight after quitting. Studies of nicotine in mice[66] suggest it may play a role in weight-loss that is independent of appetite and studies involving the elderly suggest that nicotine affects not only weight loss, but also prevents some weight gain.[67]

See also

References

  1. ^ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 Oct 2023.
  2. ^ "Determination of the Nicotine Content of Various Edible Nightshades (Solanaceae) and Their Products and Estimation of the Associated Dietary Nicotine Intake". Retrieved 2008-10-05.
  3. ^ "Smoking and Tobacco Control Monograph No. 9" (PDF).
  4. ^ The Chemical Components of Tobacco and Tobacco Smoke
  5. ^ Some Pesticides Permitted in Organic Gardening
  6. ^ American Heart Association and Nicotine addiction.
  7. ^ Connolly, G. N.; Alpert, H. R.; Wayne, G. F.; Koh, H. (2007). "Trends in nicotine yield in smoke and its relationship with design characteristics among popular US cigarette brands, 1997-2005". Tobacco Control. 16 (5): e5. doi:10.1136/tc.2006.019695. PMID 17897974. {{cite journal}}: line feed character in |author= at position 17 (help)CS1 maint: multiple names: authors list (link)
  8. ^ Jack E. Henningfield; Mitch Zeller (2006). ""Nicotine psychopharmacology", research contributions to United States and global tobacco regulation: A look back and a look forward" (PDF). 184 (3–4): 286–291. doi:10.1007/s00213-006-0308-4. {{cite journal}}: Cite journal requires |journal= (help)CS1 maint: multiple names: authors list (link)
  9. ^ Melsens (1844). "Über das Nicotin". Journal für Praktische Chemie. 32 (1): 372–377. doi:10.1002/prac.18440320155.
  10. ^ http://medicolegal.tripod.com/toxicchemicals.htm Comptes rendus, 1903, 137, p 860
  11. ^ "Optical activity and living matter".
  12. ^ "Interindividual variability in the metabolism and cardiovascular effects of nicotine in man".
  13. ^ "Metabolism and Disposition Kinetics of Nicotine".
  14. ^ http://jpet.aspetjournals.org/cgi/content/abstract/310/3/1208
  15. ^ Xinan Xiu, Nyssa L. Puskar, Jai A. P. Shanata, Henry A. Lester & Dennis A. Dougherty. Nicotine binding to brain receptors requires a strong cation– interaction. Nature 458, 534-537 (26 March 2009)
  16. ^ a b Herraiz T, Chaparro C (2005). "Human monoamine oxidase is inhibited by tobacco smoke: beta-carboline alkaloids act as potent and reversible inhibitors". Biochem. Biophys. Res. Commun. 326 (2): 378–86. doi:10.1016/j.bbrc.2004.11.033. PMID 15582589.
  17. ^ Fowler JS, Volkow ND, Wang GJ; et al. (1998). "Neuropharmacological actions of cigarette smoke: brain monoamine oxidase B (MAO B) inhibition". J Addict Dis. 17 (1): 23–34. PMID 9549600. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  18. ^ Wüllner U, Gündisch D, Herzog H; et al. (2008). "Smoking upregulates alpha4beta2* nicotinic acetylcholine receptors in the human brain". Neurosci. Lett. 430 (1): 34–7. doi:10.1016/j.neulet.2007.10.011. PMID 17997038. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  19. ^ Walsh H, Govind AP, Mastro R; et al. (2008). "Up-regulation of nicotinic receptors by nicotine varies with receptor subtype". J. Biol. Chem. 283 (10): 6022–32. doi:10.1074/jbc.M703432200. PMID 18174175. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link)
  20. ^ Nguyen HN, Rasmussen BA, Perry DC (2003). "Subtype-selective up-regulation by chronic nicotine of high-affinity nicotinic receptors in rat brain demonstrated by receptor autoradiography". J. Pharmacol. Exp. Ther. 307 (3): 1090–7. doi:10.1124/jpet.103.056408. PMID 14560040.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  21. ^ Pons S, Fattore L, Cossu G; et al. (2008). "Crucial role of alpha4 and alpha6 nicotinic acetylcholine receptor subunits from ventral tegmental area in systemic nicotine self-administration". J. Neurosci. 28 (47): 12318–27. doi:10.1523/JNEUROSCI.3918-08.2008. PMID 19020025. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  22. ^ Yoshida T, Sakane N, Umekawa T, Kondo M (1994). "Effect of nicotine on sympathetic nervous system activity of mice subjected to immobilization stress". Physiol Behav. 55 (1): 53–7. doi:10.1016/0031-9384(94)90009-4. PMID 8140174. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  23. ^ King G, Yerger VB, Whembolua GL, Bendel RB, Kittles R, Moolchan ET. Link between facultative melanin and tobacco use among African Americans.(2009). Pharmacol Biochem Behav. 92(4):589-96. doi:10.1016/j.pbb.2009.02.011 PMID 19268687
  24. ^ Elaine N. Marieb and Katja Hoehn (2007). Human Anatomy & Physiology (7th Ed.). Pearson. pp. ?. ISBN 0-805-35909-5.
  25. ^ Effective Clinical Tobacco Intervention, Thereputics Letter, issue 21, September-October 1997, University of British Colombia
  26. ^ Gilbert Lagrue, François Lebargy, Anne Cormier, "From nicotinic receptors to smoking dependence: therapeutic prospects" Alcoologie et Addictologie Vol. : 23, N° : 2S, juin 2001, pages 39S - 42
  27. ^ Jean-Claude Orsini, "Dependence on tobacco smoking and brain systems controlling glycemia and appetite" Alcoologie et Addictologie Vol. : 23, N° : 2S, juin 2001, pages 28S - 36S
  28. ^ Smokers lose their appetite : Media Releases : News : The University of Melbourne
  29. ^ Chemically Correct: Nicotine, Andrew Novick
  30. ^ Rusted, J (1994-05-05). "Does nicotine improve cognitive function?". Psychopharmacology (115). Springer-Verlag: 547–549. Retrieved 2008-11-15. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  31. ^ http://chronicle.uchicago.edu/020328/nicotine.shtml
  32. ^ a b Kenny PJ, Markou A (2006). "Nicotine self-administration acutely activates brain reward systems and induces a long-lasting increase in reward sensitivity". Neuropsychopharmacology. 31 (6): 1203–11. doi:10.1038/sj.npp.1300905. PMID 16192981. However, these effects are an illusion brought about by Nicotine addiction. What appears to be relaxation, is merely the effect of ending the craving for Nicotine. The longer the periods between Nicotine intake, the greater the illusion of pleasure will be. {{cite journal}}: Unknown parameter |month= ignored (help)
  33. ^ Erowid Nicotine Vault : Dosage
  34. ^ Einstein, Stanley (1989). Drug and Alcohol Use: Issues and Factors. Springer. pp. 101–118. ISBN 0306413787.
  35. ^ Guillem K, Vouillac C, Azar MR; et al. (2005). "Monoamine oxidase inhibition dramatically increases the motivation to self-administer nicotine in rats". J. Neurosci. 25 (38): 8593–600. doi:10.1523/JNEUROSCI.2139-05.2005. PMID 16177026. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  36. ^ Villégier AS, Blanc G, Glowinski J, Tassin JP (2003). "Transient behavioral sensitization to nicotine becomes long-lasting with monoamine oxidases inhibitors". Pharmacol. Biochem. Behav. 76 (2): 267–74. PMID 14592678. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  37. ^ NIDA - Research Report Series - Tobacco Addiction - Extent, Impact, Delivery, and Addictiveness
  38. ^ Nolley EP, Kelley BM (2007). "Adolescent reward system perseveration due to nicotine: studies with methylphenidate". Neurotoxicol Teratol. 29 (1): 47–56. doi:10.1016/j.ntt.2006.09.026. PMID 17129706.
  39. ^ Okamoto M, Kita T, Okuda H, Tanaka T, Nakashima T (1994). "Effects of aging on acute toxicity of nicotine in rats". Pharmacol Toxicol. 75 (1): 1–6. PMID 7971729. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  40. ^ IPCS INCHEM
  41. ^ http://learn.genetics.utah.edu/content/addiction/drugs/overdose.html
  42. ^ http://www.drugtext.org/library/articles/coffin.htm
  43. ^ Lockhart LP (1933). "Nicotine poisoning". Br Med J. 1: 246–7.
  44. ^ a b "Toxicology". Retrieved 2008-10-05. {{cite web}}: Text "eBasedTreatment" ignored (help)
  45. ^ a b Cohen, David J. (2001). "Impact of Smoking on Clinical and Angiographic Restenosis After Percutaneous Coronary Intervention". Circulation. 104: 773. doi:10.1161/hc3201.094225. PMID 11502701. Retrieved 2006-11-06. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  46. ^ Longmore, M., Wilkinson, I., Torok, E. Oxford Handbook of Clinical Medicine (Fifth Edition) p. 232
  47. ^ Green JT, Richardson C, Marshall RW; et al. (2000). "Nitric oxide mediates a therapeutic effect of nicotine in ulcerative colitis". Aliment Pharmacol Ther. 14 (11): 1429–34. doi:10.1046/j.1365-2036.2000.00847.x. PMID 11069313. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  48. ^ "Smoking Cuts Risk of Rare Cancer". UPI. March 29, 2001. Retrieved 2006-11-06.
  49. ^ Recer, Paul (May 19, 1998). "Cigarettes May Have an Up Side". AP. Retrieved 2006-11-06.
  50. ^ Lain, Kristine Y. (1991). "Urinary cotinine concentration confirms the reduced risk of preeclampsia with tobacco exposure". American Journal of Obstetrics and Gynecology. 181 (5): 908–14. PMID 11422156. Retrieved 2006-11-06. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help); line feed character in |coauthors= at position 79 (help)
  51. ^ Hjern, A (2001). "Does tobacco smoke prevent atopic disorders? A study of two generations of Swedish residents". Clin Exp Allergy. 31 (6): 908–14. doi:10.1046/j.1365-2222.2001.01096.x. PMID 11422156. Retrieved 2006-11-06. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  52. ^ Lisa Melton (2006). "Body Blazes". Scientific American: 24. {{cite journal}}: Unknown parameter |month= ignored (help)
  53. ^ Parkinson's Disease: The Newest Advances
  54. ^ Fratiglioni, L (2000). "Smoking and Parkinson's and Alzheimer's disease: review of the epidemiological studies". Behav Brain Res. 113 (1–2): 117–20. doi:10.1016/S0166-4328(00)00206-0. PMID 10942038. {{cite journal}}: |access-date= requires |url= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  55. ^ Thompson, Carol. "Alzheimer's disease is associated with non-smoking". Retrieved 2006-11-06.
  56. ^ Thompson, Carol. "Parkinson's disease is associated with non-smoking". Retrieved 2006-11-06.
  57. ^ "Alzheimer's Starts Earlier for Heavy Drinkers, Smokers". Reuters. 2008-04-17. Retrieved 2008-06-27.
  58. ^ Peck, Peggy (2002-07-25). "Smoking Significantly Increases Risk of Alzheimer's Disease Among Those Who Have No Genetic Predisposition". Retrieved 2008-06-27.
  59. ^ Aggarwal NT, Bienias JL, Bennett DA; et al. (2006). "The relation of cigarette smoking to incident Alzheimer's disease in a biracial urban community population". Neuroepidemiology. 26 (3): 140–6. doi:10.1159/000091654. PMID 16493200. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  60. ^ Lerche Davis,, Jeanie (2004-03-22). "Smoking Speeds Dementia, Alzheimer's Disease". Retrieved 2008-06-27.{{cite web}}: CS1 maint: extra punctuation (link)
  61. ^ "Nicotine as an antiepileptic agent in ADNFLE: An n-of-one study".
  62. ^ de Leon J, Tracy J, McCann E, McGrory A, Diaz FJ (2002). "Schizophrenia and tobacco smoking: a replication study in another US psychiatric hospital". Schizophr Res. 56 (1–2): 55–65. doi:10.1016/S0920-9964(01)00192-X. PMID 12084420. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  63. ^ de Leon J, Dadvand M, Canuso C, White AO, Stanilla JK, Simpson GM (1995). "Schizophrenia and smoking: an epidemiological survey in a state hospital". Am J Psychiatry. 152 (3): 453–5. PMID 7864277. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  64. ^ Aguilar MC, Gurpegui M, Diaz FJ, de Leon J (2005). "Nicotine dependence and symptoms in schizophrenia: naturalistic study of complex interactions". Br J Psychiatry. 186: 215–21. doi:10.1192/bjp.186.3.215. PMID 15738502. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  65. ^ "Attention-Deficit Hyperactivity Disorder". Reuters Health. Reuters. 2001. Archived from the original on 2006-04-26. Nicotine improves ADHD symptoms. Although such findings should certainly not encourage anyone to smoke, some studies are focusing on benefits of nicotine therapy in adults with ADHD. {{cite web}}: Unknown parameter |month= ignored (help)
  66. ^ Schechter MD, Cook PG (1976). "Nicotine-induced weight loss in rats without an effect on appetite". Eur J Pharmacol. 38 (1): 63–9. doi:10.1016/0014-2999(76)90201-6. PMID 954834. {{cite journal}}: Unknown parameter |month= ignored (help)
  67. ^ Cigarette Smoking and Weight Loss in Nursing Home Residents [1]


45. Suemaru K, Kohnomi S, Umeda K H (2008). "[Evaluation of antipsychotic and relative drugs using disruption of prepulse inhibition as an animal model for schizophrenia]". Nihon Shinkei Seishin Yakurigaku Zasshi (in Japanese). 28 (3): 121–6. PMID 18646597. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link) 46. De Luca V, Wong AH, Muller DJ, Wong GW, Tyndale RF, Kennedy JL (2004). "Evidence of association between smoking and alpha7 nicotinic receptor subunit gene in schizophrenia patients". Neuropsychopharmacology. 29 (8): 1522–6. doi:10.1038/sj.npp.1300466. PMID 15100704. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)

External links

Further reading

  • Bilkei-Gorzo A, Rácz I, Michel K, Darvas M, Rafael Maldonado López, Zimmer A. (2008 63: 164-71). "A common genetic predisposition to stress sensitivity and stress-induced nicotine craving". Biol. Psychiatry. {{cite journal}}: Check date values in: |year= (help)CS1 maint: multiple names: authors list (link)

Template:Parasympathomimetics

Retrieved from "https://en.wikipedia.org/w/index.php?title=Nicotine&oldid=313160344"