Monoamine oxidase inhibitor

From Wikipedia, the free encyclopedia

Monoamine oxidase inhibitors (MAOIs) are chemicals which inhibit the activity of the monoamine oxidase enzyme family. They have a long history of use as medications prescribed for the treatment of depression. They are particularly effective in treating atypical depression.[citation needed]

Because of potentially lethal dietary and drug interactions, monoamine oxidase inhibitors have historically been reserved as a last line of treatment, used only when other classes of antidepressant drugs (for example selective serotonin reuptake inhibitors and tricyclic antidepressants) have failed.[1] A transdermal patch form of the MAOI selegiline, called Emsam, was approved for use by the Food and Drug Administration in the United States on February 28, 2006.[2]

New research into MAOIs indicate that much of the concern over their dangerous dietary side effects stems from misconceptions and misinformation, and that despite proven effectiveness of this class of drugs, it is underutilized and misunderstood in the medical profession. [3] New research also questions the validity of the perceived severity of dietary reactions, which has historically been based on outdated research. [4]



[edit] Indications

In the past, MAOIs were prescribed for those resistant to tricyclic antidepressant therapy.[citation needed] Newer MAOIs such as selegiline (typically used in the treatment of Parkinson's disease) and the reversible MAOI moclobemide provide a safer alternative[5] and are now sometimes used as first-line therapy. However, these substances are not always as effective as their predecessors.[citation needed]

MAOIs have been found to be effective in the treatment of panic disorder with agoraphobia, social phobia, atypical depression or mixed anxiety and depression, bulimia, and post-traumatic stress disorder, as well as borderline personality disorder. There are reports of MAOI efficacy in obsessive-compulsive disorder (OCD), trichotillomania, dysmorphophobia, and avoidant personality disorder, but these reports are from uncontrolled case reports.[5]

MAOIs can also be used in the treatment of Parkinson's disease by targeting MAO-B in particular (therefore affecting dopaminergic neurons), as well as providing an alternative for migraine prophylaxis. Inhibition of both MAO-A and MAO-B is used in the treatment of clinical depression and anxiety.

MAOIs appear to be particularly indicated for outpatients with "neurotic depression" complicated by panic disorder or hysteroid dysphoria, which involves repeated episodes of depressed mood in response to feeling rejected.[6]

[edit] Mechanism of action

MAOIs act by inhibiting the activity of monoamine oxidase, thus preventing the breakdown of monoamine neurotransmitters and thereby increasing their availability. There are two isoforms of monoamine oxidase, MAO-A and MAO-B. MAO-A preferentially deaminates serotonin, melatonin, epinephrine, and norepinephrine. MAO-B preferentially deaminates phenylethylamine and trace amines. Dopamine is equally deaminated by both types.

[edit] Reversibility

The early MAOIs inhibited monoamine oxidase irreversibly. When they react with monoamine oxidase, they permanently deactivate it, and the enzyme cannot function until it has been replaced by the body, which can take about two weeks. A few newer MAOIs, a notable one being moclobemide, are reversible, meaning that they are able to detach from the enzyme to facilitate usual catabolism of the substrate. The level of inhibition in this way is governed by the concentrations of the substrate and the MAOI.

Harmaline found in Peganum harmala, as well as the Ayahausca vine, Banisteriopsis caapi, and Passiflora incarnata are reversible inhibitors of MAO-A (RIMA).[7]

[edit] Selectivity

In addition to reversibility, MAOIs differ by their selectivity of the MAO receptor. Some MAOIs inhibit both MAO-A and MAO-B equally, other MAOIs have been developed to target one over the other.

MAO-A inhibition reduces the breakdown of primarily serotonin, norepinephrine, and dopamine; selective inhibition of MAO-A allows for tyramine to be metabolised via MAO-B.[8] Agents that act on serotonin if taken with another serotonin-enhancing agent may result in a potentially fatal interaction called serotonin syndrome or with irreversible and unselective inhibitors (such as older MAOIs), of MAO a hypertensive crisis as a result of tyramine food interactions is particularly problematic with older MAOIs. Tyramine is broken down by MAO-A and MAO-B, therefore inhibiting this action may result in excessive build-up of it, so diet must be monitored for tyramine intake.

MAO-B inhibition reduces the breakdown mainly of dopamine and phenethylamine so there are no dietary restrictions associated with this. MAO-B would also metabolize tyramine, as the only differences between dopamine, phenethylamine, and tyramine are two phenylhydroxyl groups on carbons 3 and 4. The 4-OH would not be a steric hindrance to MAO-B on tyramine.[9] Two MAO-Bi drugs, selegiline and rasagiline have been approved by the FDA without dietary restrictions, except in high-dosage treatment, wherein they lose their selectivity.[2][10]

[edit] Dangers

When ingested orally, MAOIs inhibit the catabolism of dietary amines. When foods containing tyramine are consumed (so-called "cheese effect"), the individual may suffer from hypertensive crisis. If foods containing tryptophan are consumed, hyperserotonemia may result. The amount required to cause a reaction varies greatly from individual to individual, and depends on the degree of inhibition, which in turn depends on dosage and selectivity.

The exact mechanism by which tyramine causes a hypertensive reaction is not well-understood, but it is assumed that tyramine displaces norepinephrine from the storage vesicles.[11] This may trigger a cascade in which excessive amounts of norepinephrine can lead to a hypertensive crisis. Another theory suggests that proliferation and accumulation of catecholamines causes hypertensive crisis[12]

Tyrosine, not tyramine, is the precursor to catecholamines. Tyramine is a breakdown product of tyrosine. In the gut and during fermentation, tyrosine, an amino acid, is decarboxylated to tyramine. Under ordinary circumstances, tyramine is deaminated in the liver to an inactive metabolite, but, when the hepatic MAO (primarily MAO-A) is inhibited, the "first-pass" clearance of tyramine is blocked and circulating tyramine levels can climb. Elevated tyramine competes with tyrosine for transport across the blood–brain barrier (via aromatic amino acid transport) where it can then enter adrenergic nerve terminals. Once in the cytoplasmic space, tyramine will be transported via the vesicular monoamine transporter (VMAT) into synaptic vesicles, thereby displacing norepinephrine. The mass transfer of norepinephrine from its vesicular storage space into the extracellular space via mass action can precipitate the hypertensive crisis. Hypertensive crises can sometimes result in stroke or cardiac arrhythmia if not treated. In general, this risk is not present with RIMAs. Both kinds of intestinal MAO inhibition can cause hyperpyrexia, nausea, and psychosis if foods high in levodopa are consumed.

Examples of foods and drinks with potentially high levels of tyramine include liver and fermented substances, such as alcoholic beverages and aged cheeses.[13] (See a List of foods containing tyramine). Examples of levodopa-containing foods include broad beans. These diet restrictions are not necessary for those taking selective MAO-B inhibitors, unless these are being taken in high dosages, as mentioned above.

It deserves separate mention that some meat extracts and yeast extracts (Bovril, Marmite, Vegemite) contain extremely high levels of tyramine, and should not be used with these medications.

When MAOIs were first introduced, these risks were not known, and, over the following four decades, fewer than 100 people have died from hypertensive crisis.[citation needed] Presumed due to the sudden onset and violent appearance of the reaction, MAOIs gained a reputation for being so dangerous that, for a while, they were taken off the market in America entirely. However, it is now believed that, used as directed under the care of a qualified psychiatrist, this class of drugs is a viable alternative treatment for intermediate- to long-term use.

The most significant risk associated with the use of MAOIs is the potential for interactions with over-the-counter and prescription medicines, illicit drugs or medications, and some supplements (e.g., St. John's Wort). It is vital that a doctor supervise such combinations to avoid adverse reactions. For this reason, many users carry an MAOI-card, which lets emergency medical personnel know what drugs to avoid. (E.g., adrenaline dosage should be reduced by 75%, and duration is extended.)[13] The risk of the interaction of MAOI medications with other drugs or certain foods is particularly dangerous because those on the medication who would have to restrict their diets often are depressed patients who "don't care if they live or die."[14]

MAOIs should not be combined with other psychoactive substances (antidepressants, painkillers, stimulants, both legal and illegal etc.) except under expert care. Certain combinations can cause lethal reactions, common examples including SSRIs, tricyclics, MDMA, meperidine,[15] tramadol, and dextromethorphan[citation needed]. Agents with actions on epinephrine, norepinephrine, or dopamine must be administered at much lower doses due to potentiation and prolonged effect.

Nicotine, a substance frequently implicated in tobacco addiction, has been shown to have "relatively weak" addictive properties when administered alone.[16] The addictive potential increases dramatically after co-administration of an MAOI, which specifically causes sensitization of the locomotor response in rats, a measure of addictive potential.[17][18] This may be reflected in the difficulty of smoking cessation, as tobacco contains naturally-occurring MAOI compounds in addition to the nicotine.[19][20][21]

[edit] Withdrawal

Antidepressants including MAOIs have some dependence-producing effects, the most notable one being a withdrawal syndrome, which may be severe especially if MAOIs are discontinued abruptly or over-rapidly. However, the dependence-producing potential of MAOIs or antidepressants in general is not as significant as benzodiazepines. For example, antidepressants have significantly less abuse potential than benzodiazepines. Withdrawal symptoms can be managed by a gradual reduction in dosage over a period of weeks, months or years to minimize or prevent withdrawal symptoms.[22]

MAOIs, as with any antidepressant medications, do not alter the course of the disorder, so it is possible that discontinuation can return the patient to the pre-treatment state.[23]

This consideration greatly complicates switching a patient between a MAOI and a SSRI, because it is necessary to clear the system completely of one drug before starting another. If one also tapers dosage gradually, the result is that for weeks a depressed patient will have to bear the depression without chemical help during the drug-free interval. This may be preferable to risking the effects of an interaction between the two drugs, but it is often not easy for the patient[citation needed].

[edit] Interactions

The MAOIs are infamous for their numerous drug interactions. Unless the interaction is desired, any drug that falls within the following classifications should be avoided:

Such substances include:

It is recommended by the FDA to contact a physician or pharmacist before taking any drug while on an MAOI.

[edit] History

The older MAOIs' heyday was mostly between the years 1957 and 1970.[8] The initial popularity of the 'classic' non-selective irreversible MAO inhibitors began to wane due to their serious interactions with sympathomimetic drugs and tyramine-containing foods that could lead to dangerous hypertensive emergencies. As a result, the use by medical practitioners of these older MAOIs declined. When scientists discovered that there are two different MAO enzymes (MAO-A and MAO-B), they developed selective compounds for MAO-B, (for example, selegiline, which is used for Parkinson's disease), to reduce the side-effects and serious interactions. Further improvement occurred with the development of compounds (moclobemide and toloxatone) that not only are selective but cause reversible MAO-A inhibition and a reduction in dietary and drug interactions.[24]

Irreversible MAOIs were the first antidepressants to be discovered, but they fell out of favour with the advent of the discovery of safer antidepressants; these newer antidepressant drug classes have fewer adverse effects, especially the dangerous irreversible MAOI food interaction with tyramine, sometimes referred to as the 'cheese syndrome', which leads to dangerous hypertension. However, reversible MAOIs lack these hypertensive adverse effects.[25] Moclobemide, was the first reversible inhibitor of MAO-A to enter widespread clinical practice; its reversible inhibitory features give it a number of advantages over the older irreversible MAO inhibitors.[26]

[edit] List of MAOIs

  • Antiparasitic
    • Invertebrate MAO Inhibitors
      • Amitraz antiparasitic used in animals for ticks, mites (sarcoptes, demodex) and lice. Used on plants as an insecticide against mites, aphids, etc.

Various tryptamine and phenethylamine/amphetamine derivatives such as αET, αMT, amphetamine (itself), methamphetamine, MDMA, 4-MTA, PMA, 2C-T-7, and 2C-T-21 may also have weak to strong MAOI effects at high doses. Many other unlisted hydrazines like hydrazine (itself), monomethylhydrazine, and phenylhydrazine have some MAOI properties as well.

[edit] See also

[edit] References

This article needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. (February 2010)
  1. ^ Mayo Clinic Staff, "Depression (major depression): Treatment and drugs"
  2. ^ a b "FDA Approves Emsam (Selegiline) as First Drug Patch for Depression." (Press release). U.S. Food and Drug Administration. 2006-02-28. Retrieved 2009-11-19.
  3. ^ Grady, Meghan M.; Meghan M. Grady and Stephen M. Stah (2012). "Practical guide for prescribing MAOIs: debunking myths and removing barriers". CNS Spectrums 17: 17, pp 2–10. doi:10.1017/S109285291200003X.
  4. ^ "Tyramine in foods and monoamine oxidase inhibitor drugs: A crossroad where medicine, nutrition, pharmacy, and food industry converge". Journal of Food Composition and Analysis 19 (2006) S58–S65.
  5. ^ a b Liebowitz MR, Hollander E, Schneier F, et al. (1990). "Reversible and irreversible monoamine oxidase inhibitors in other psychiatric disorders". Acta Psychiatr Scand Suppl 360: 29–34. doi:10.1111/j.1600-0447.1990.tb05321.x. PMID 2248064.
  6. ^ Dowson, JH (1987). "MAO inhibitors in mental disease: their current status. [Review]". Journal of Neural Transmission. Supplementum 23: 121–38. PMID 3295114.
  7. ^ Edward J. Massaro, Handbook of Neurotoxicology
  8. ^ a b Nowakowska E, Chodera A (July 1997). "[Inhibitory monoamine oxidases of the new generation]". Pol. Merkur. Lekarski (in Polish) 3 (13): 1–4. PMID 9432289.
  9. ^ ScienceDirect - Archives of Biochemistry and Biophysics : Structural insights into the mechanism of amine oxidation by monoamine oxidases A and B
  10. ^ BLTC Research [1] (2006). "Rasagiline: a neuroprotective smart drug?". The Good Drug Guide. Retrieved 2007-12-02. "At dosages above around 2 mg per day, rasagiline loses its selectivity for MAO type B and also inhibits MAO type A. An MAO-B selective regimen does not cause significant tyramine potentiation, the dreaded 'cheese effect' common to users of older unselective and irreversible MAOIs who eat tyramine-rich foods. This will be taken with and without foo. Thus, low-dosage rasagiline demands no special dietary restrictions."
  11. ^ Jacob, Giris; Gamboa, Alfredo; Diedrich, André; Shibao, Cyndya; Robertson, David; Biaggioni, Italo (August 2005). "Tyramine-Induced Vasodilation Mediated by Dopamine Contamination: A Paradox Resolved". Hypertension (Lippincott Williams & Wilkins) 46 (2): 358. doi:10.1161/01.HYP.0000172353.62657.8b. PMID 15967868. Retrieved 2007-12-02. "Tyramine displaces norepinephrine from neuronal vesicles into the axoplasm, and it is likely that some of it is converted to DHPG, and only a portion reaches the circulation."
  12. ^ A.J Giannini. Psychotropic Drug Overdose. In M.E. Keshavan,J.S. Jennedy. (eds) Drug-Induced Dysfunction in Psychiatry. NY, Hemisphere Publishing,1992, pg. 41. ISBN 0-89116-961-X
  13. ^ a b Mosher, Clayton James, and Scott Akins. Drugs and Drug Policy : The Control of Consciousness Alteration. Thousand Oaks, Calif.: Sage, 2007.
  14. ^ Kramer, Peter D. Listening to Prozac. New York, N.Y., U.S.A.: Viking, 1993.
  15. ^ Pharmacology from H.P. Rang, M.M. Dale, J.M. Ritter, P.K. Moore, year 2003, chapter 38
  16. ^ Guillem K, Vouillac C, Azar MR, et al. (September 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.
  17. ^ Villégier AS, Blanc G, Glowinski J, Tassin JP (September 2003). "Transient behavioral sensitization to nicotine becomes long-lasting with monoamine oxidases inhibitors". Pharmacol. Biochem. Behav. 76 (2): 267–74. doi:10.1016/S0091-3057(03)00223-5. PMID 14592678.
  18. ^ Amsterdam, J. V.; Talhout, R.; Vleeming, W.; Opperhuizen, A. (2006). "Contribution of monoamine oxidase (MAO) inhibition to tobacco and alcohol addiction". Life Sciences 79 (21): 1969–1973. doi:10.1016/j.lfs.2006.06.010. PMID 16884739. edit
  19. ^ Berlin, I.; m. Anthenelli, R. (2001). "Monoamine oxidases and tobacco smoking". The International Journal of Neuropsychopharmacology 4 (1): 33–42. doi:10.1017/S1461145701002188. PMID 11343627. edit
  20. ^ Fowler, J. S.; Volkow, N. D.; Wang, G. J.; Pappas, N.; Logan, J.; Shea, C.; Alexoff, D.; MacGregor, R. R. et al. (1996). "Brain monoamine oxidase a inhibition in cigarette smokers". Proceedings of the National Academy of Sciences of the United States of America 93 (24): 14065–14069. doi:10.1073/pnas.93.24.14065. PMC 19495. PMID 8943061. edit
  21. ^ Fowler, J. S.; Volkow, N. D.; Wang, G.-J.; Pappas, N.; Logan, J.; MacGregor, R.; Alexoff, D.; Shea, C. et al. (1996). "Inhibition of monoamine oxidase B in the brains of smokers". Nature 379 (6567): 733–736. doi:10.1038/379733a0. ISSN 0028-0836. PMID 8602220.
  22. ^ van Broekhoven F, Kan CC, Zitman FG (June 2002). "Dependence potential of antidepressants compared to benzodiazepines". Prog. Neuropsychopharmacol. Biol. Psychiatry 26 (5): 939–43. doi:10.1016/S0278-5846(02)00209-9. PMID 12369270.
  23. ^ Dobson, K. S.; et al., Steven D.; Dimidjian, Sona; Schmaling, Karen B.; Kohlenberg, Robert J.; Gallop, Robert J.; Rizvi, Shireen L.; Gollan, Jackie K. et al. (2008). "Randomized Trial of Behavioral Activation, Cognitive Therapy, and Antidepressant Medication in the Prevention of Relapse and Recurrence in Major Depression". Journal of Consulting and Clinical Psychology 76 (3): 468–77. doi:10.1037/0022-006X.76.3.468. PMC 2648513. PMID 18540740.
  24. ^ Livingston MG, Livingston HM (April 1996). "Monoamine oxidase inhibitors. An update on drug interactions". Drug Saf 14 (4): 219–27. doi:10.2165/00002018-199614040-00002. PMID 8713690.
  25. ^ Nair NP, Ahmed SK, Kin NM (November 1993). "Biochemistry and pharmacology of reversible inhibitors of MAO-A agents: focus on moclobemide". J Psychiatry Neurosci 18 (5): 214–25. PMC 1188542. PMID 7905288.
  26. ^ Baldwin D, Rudge S (1993). "Moclobemide: a reversible inhibitor of monoamine oxidase type A". Br J Hosp Med 49 (7): 497–9. PMID 8490690.
  27. ^ Tomas Herraiz, Carolina Chaparro. Human monoamine oxidase enzyme inhibition by coffee and β-carbolines norharman and harman isolated from coffee. Life Sciences. 2006;78(8):795–802. doi:10.1016/j.lfs.2005.05.074. PMID 16139309.
  28. ^ Herraiza T, Gonzáleza D, Ancín-Azpilicuetac C, Aránb VJ, Guillén H. β-Carboline alkaloids in Peganum harmala and inhibition of human monoamine oxidase (MAO). Food and Chemical Toxicology. 2010;48(3):839–845. doi:10.1016/j.fct.2009.12.019. PMID 20036304.
  29. ^ Yong Nam Han, Shi Yong Ryu, Byung Hoon Han. Antioxidant activity of resveratrol closely correlates with its monoamine oxidase-A inhibitory activity. Archives of Pharmacal Research. 1990;13(2):132–135. doi:10.1007/BF02857789.
  30. ^ Ying Xu, Bao-Shan Ku, Hai-Yan Yao, Yan-Hua Lin, Xing Ma, Yong-He Zhang, Xue-Jun Li. The effects of curcumin on depressive-like behaviors in mice. European Journal of Pharmacology. 2005;518(1):40–46. doi:10.1016/j.ejphar.2005.06.002. PMID 15987635.
  31. ^ van Diermen D, Marston A, Bravo J, Reist M, Carrupt PA, Hostettmann K. Monoamine oxidase inhibition by Rhodiola rosea L. roots. Journal of Ethnopharmacology. 2009 Mar 18;122(2):397–401. doi:10.1016/j.jep.2009.01.007. PMID 19168123.
  32. ^ Stafford GI, Pedersen PD, Jäger AK, van Staden J. Monoamine oxidase inhibition by southern African traditional medicinal plants. South African Journal of Botany. 2007;73(3):384–390. doi:10.1016/j.sajb.2007.03.001.
  33. ^ White HL, Scates PW, Cooper BR. Extracts of Ginkgo biloba leaves inhibit monoamine oxidase. Life Science. 1996;58(16):1315–21. doi:10.1016/0024-3205(96)00097-5. PMID 8614288.
  34. ^ Dreiseitel A, Korte G, Schreier P, et al. (May 2009). "Berry anthocyanins and their aglycons inhibit monoamine oxidases A and B". Pharmacol. Res. 59 (5): 306–11. doi:10.1016/j.phrs.2009.01.014. PMID 19416630.
  35. ^ Xu Y, Li S, Chen R, et al. (January 2010). "Antidepressant-like effect of low molecular proanthocyanidin in mice: involvement of monoaminergic system". Pharmacol. Biochem. Behav. 94 (3): 447–53. doi:10.1016/j.pbb.2009.10.007. PMID 19857512.
  36. ^ Shyh-Mirn Lin, Shih-Wei Wang, Su-Chen Ho, Ya-Li Tang. Protective effect of green tea (-)-epigallocatechin-3-gallate against the monoamine oxidase B enzyme activity increase in adult rat brains. Nutrition. 2010;26(11–12):1195–1200. doi:10.1016/j.nut.2009.11.022.
  37. ^ LD Konga, Christopher HK Chengb, RX Tan. Inhibition of MAO A and B by some plant-derived alkaloids, phenols and anthraquinones. Journal of Ethnopharmacology. 2004;91(2–3):351–355. doi:10.1016/j.jep.2004.01.013.
  38. ^ Hiroyuki Haraguchi, Yasumasa Tanaka, Amal Kabbash, Toshihiro Fujioka, Takashi Ishizu, Akira Yagi. Monoamine oxidase inhibitors from Gentiana lutea. Phytochemistry. 2004;65(15):2255–2260. doi:10.1016/j.phytochem.2004.06.025.
  39. ^ Zion v. New York Hospital, 1994
  40. ^ Court TV coverage, 1994
  41. ^ Lerner, Barron H. (November 8, 2006). "The case that shook medicine". Washington Post.
  42. ^ Robert Morgenthau, Manhattan District Attorney May 1986
  43. ^ MTCMA Training manual "Effects of Sleep Deprivation on Fire Fighters and EMS Responders"
  44. ^ Robins, Natalie (1995). The Girl Who Died Twice. New York: Delacorte Press. ISBN 0-385-30809-4.
Sympatholytic (and closely related) antihypertensives (C02)