Monoamine oxidase inhibitor
Monoamine oxidase inhibitors (MAOIs) are a class of drugs that inhibit the activity of one or both monoamine oxidase enzymes: monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B). They are best known as powerful anti-depressants, as well as effective therapeutic agents for panic disorder and social phobia. They are particularly effective in treatment-resistant depression and atypical depression. They are also used in the treatment of Parkinson's disease and several other disorders.
|Monoamine oxidase inhibitor|
|Use||Treatment of major depressive disorder, atypical depression, Parkinson's disease, and several other disorders|
|Mechanism of action||Enzyme inhibitor|
|Biological target||Monoamine oxidase enzymes:
MAO-A and/or MAO-B
Reversible inhibitors of monoamine oxidase A (RIMAs) are a subclass of MAOIs that selectively and reversibly inhibit the MAO-A enzyme. RIMAs are used clinically in the treatment of depression and dysthymia. As they are safer in single-drug overdose, they do not approach the monoamine levels of the older, irreversible MAOIs like phenelzine and tranylcypromine. RIMAs have not gained widespread market share in the United States. Due to their reversibility, RIMAs are weaker than irreversible MAOIs in increasing the monoamines important in depressive disorder.
New research into MAOIs indicates that much of the concern over their supposed dangerous dietary side effects stems from misconceptions and misinformation, and that it is still underutilized despite demonstrated efficacy. New research also questions the validity of the perceived severity of dietary reactions, which has been based on outdated research. Despite this, many psychiatrists still reserve monoamine oxidase inhibitors 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.
Newer MAOIs such as selegiline (typically used in the treatment of Parkinson's disease) and the reversible MAOI moclobemide provide a safer alternative and are now sometimes used as first-line therapy.
MAOIs have been found to be effective in the treatment of panic disorder with agoraphobia, social phobia, atypical depression or mixed anxiety disorder and depression, bulimia, and post-traumatic stress disorder, as well as borderline personality disorder. MAOIs appear to be particularly effective in the management of bipolar depression according to a recent retrospective-analysis. 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.
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 dysthymia complicated by panic disorder or hysteroid dysphoria, which involves repeated episodes of depressed mood in response to feeling rejected.
People taking MAOIs generally need to change their diets to limit or avoid foods and beverages containing tyramine. If large amounts of tyramine are consumed, they may suffer hypertensive crisis, which can be fatal. Examples of foods and beverages with potentially high levels of tyramine include animal liver and fermented substances, such as alcoholic beverages and aged cheeses. Excessive concentrations of tyramine in blood plasma can lead to hypertensive crisis by increasing the release of norepinephrine (NE), which causes blood vessels to constrict by activating alpha-1 adrenergic receptors. Ordinarily, MAO-A would destroy the excess NE; when MAO-A is inhibited, however, NE levels get too high, leading to dangerous increases in blood pressure.
RIMAs are displaced from MAO-A in the presence of tyramine, rather than inhibiting its breakdown in the liver as general MAOIs do. Additionally, MAO-B remains free and continues to metabolize tyramine in the stomach, although this is less significant than the liver action. Thus, RIMAs are unlikely to elicit tyramine-mediated hypertensive crisis; moreover, dietary modifications are not usually necessary when taking a reversible inhibitor of MAO-A (i.e., moclobemide) or low doses of selective MAO-B inhibitors (e.g., selegiline 6 mg/24 hours transdermal patch).
The most significant risk associated with the use of MAOIs is the potential for drug interactions with over-the-counter and prescription medicines, illicit drugs or medications, and some dietary supplements (e.g., St. John's wort, tryptophan). 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 (epinephrine) dosage should be reduced by 75%, and duration is extended.)
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, tramadol, and dextromethorphan. Drugs that affect the release or reuptake of epinephrine, norepinephrine, or dopamine typically need to be administered at lower doses due to the resulting potentiated and prolonged effect. MAOIs also interact with tobacco-containing products (e.g., cigarettes) and may potentiate the effects of certain compounds in tobacco. This may be reflected in the difficulty of smoking cessation, as tobacco contains naturally occurring MAOI compounds in addition to the nicotine.
While safer than general MAOIs, RIMAs still possess significant and potentially serious drug interactions with many common drugs; in particular, they can cause serotonin syndrome or hypertensive crisis when combined with almost any antidepressant or stimulant, common migraine medications, certain herbs, or even most cold medicines (including decongestants, antihistamines, and cough syrup).
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 too rapidly. The dependence-producing potential of MAOIs or antidepressants in general is not as significant as benzodiazepines, however. 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.
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.
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.
The MAOIs are infamous for their numerous drug interactions, including the following kinds of substances:
- Substances that are metabolized by monoamine oxidase, as they can be boosted by up to several-fold.
- Substances that increase serotonin, norepinephrine, or dopamine activity, as too much of any of these neurochemicals can result in severe acute consequences, including serotonin syndrome, hypertensive crisis, and psychosis, respectively.
Such substances that can react with MAOIs include:
- Phenethylamines: 2C-B, mescaline, phenethylamine (PEA), etc.
- Tryptamines: DMT (Prevents your body from digesting it, allowing one to experience effects by taking it orally i.e. by Ayahuasca), psilocin/psilocybin ("Magic Mushrooms"), etc.
- Norepinephrine, and/or dopamine reuptake inhibitors:
- Serotonin-norepinephrine reuptake inhibitors (SNRIs): desvenlafaxine, duloxetine, milnacipran, venlafaxine.
- Norepinephrine-dopamine reuptake inhibitors (NDRIs): amineptine, bupropion, methylphenidate, nomifensine.
- Norepinephrine reuptake inhibitors (NRIs): atomoxetine, mazindol, reboxetine.
- Tricyclic antidepressants (TCAs): amitriptyline, butriptyline, clomipramine, desipramine, dosulepin, doxepin, imipramine, lofepramine, nortriptyline, protriptyline, trimipramine.
- Tetracyclic antidepressants (TeCAs): amoxapine, maprotiline.
- Phenylpiperidine derivative opioids: meperidine/pethidine, tramadol, methadone, fentanyl, dextropropoxyphene, propoxyphene.
- Others: brompheniramine, chlorpheniramine, cocaine, cyclobenzaprine, dextromethorphan (DXM), ketamine, MDPV, nefazodone, phencyclidine (PCP), pheniramine, sibutramine, trazodone
- Serotonin, norepinephrine, and/or dopamine releasers: 4-methylaminorex (4-MAR), amphetamine, benzphetamine, cathine, cathinone, diethylcathinone, ephedrine, levmetamfetamine, lisdexamfetamine, MDMA ("Ecstasy"), methamphetamine, pemoline, phendimetrazine, phenethylamine (PEA), phentermine, propylhexedrine, pseudoephedrine, phenylephrine, tyramine.
- Local and general anesthetic in surgery and dentistry, in particular those containing epinephrine. There is no universally taught or accepted practice regarding dentistry and use of MAOIs such as phenelzine, and therefore it is vital to inform all clinicians, especially dentists, of the potential effect of MAOIs and local anesthesia. In preparation for dental work, withdrawal from phenelzine is specifically advised; since this takes two weeks, however, it is not always a desirable or practical option. Dentists using local anesthesia are advised to use a non-epinephrine anesthetic such as mepivacaine at a level of 3%. Specific attention should be paid to blood pressure during the procedure, and the level of the anesthetic should be regularly and appropriately topped-up, for non-epinephrine anesthetics take longer to come into effect and wear off faster. Patients taking phenelzine are advised to notify their psychiatrist prior to any dental treatment.
- Certain other supplements: Hypericum perforatum ("St John's wort"), inositol, Rhodiola rosea, S-adenosyl-L-methionine (SAMe), L-theanine.
- Antibiotics such as Linezolid
- Other monoamine oxidase inhibitors.
Mechanism of actionEdit
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 phenethylamine and certain other trace amines; in contrast, MAO-A preferentially deaminates other trace amines, like tyramine, whereas dopamine is equally deaminated by both types.
The early MAOIs covalently bound to the monoamine oxidase enzymes, thus inhibiting them irreversibly; the bound enzyme could not function and thus enzyme activity was blocked until the cell made new enzymes. The enzymes turn over approximately every 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.
In addition to reversibility, MAOIs differ by their selectivity of the MAO enzyme subtype. 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. 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 its excessive build-up, 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. 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.
MAOIs started off due to the serendipitous discovery that iproniazid was a potent MAO inhibitor (MAOI). Originally intended for the treatment of tuberculosis, in 1952, iproniazid's antidepressant properties were discovered when researchers noted that the depressed patients given iproniazid experienced a relief of their depression. Subsequent in vitro work led to the discovery that it inhibited MAO and eventually to the monoamine theory of depression. MAOIs became widely used as antidepressants in the early 1950s. The discovery of the 2 isoenzymes of MAO has led to the development of selective MAOIs that may have a more favorable side-effect profile.
The older MAOIs' heyday was mostly between the years 1957 and 1970. 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. Moclobemide, was the first reversible inhibitor of MAO-A to enter widespread clinical practice.
List of MAO inhibiting drugsEdit
- Nonselective MAO-A/MAO-B inhibitors
- Selective MAO-A inhibitors
- Selective MAO-B inhibitors
MAOIs that have been withdrawn from the marketEdit
- Nonselective MAO-A/MAO-B inhibitors
- Benmoxin (Nerusil, Neuralex)
- Iproclozide (Sursum)
- Iproniazid (Marsilid, Iprozid, Ipronid, Rivivol, Propilniazida) (discontinued worldwide except for France)
- Mebanazine (Actomol)
- Octamoxin (Ximaol, Nimaol)
- Pheniprazine (Catron)
- Phenoxypropazine (Drazine)
- Pivalylbenzhydrazine (Tersavid)
- Safrazine (Safra) (discontinued worldwide except for Japan)
- Caroxazone (Surodil, Timostenil)
- Selective MAO-A inhibitors
- Minaprine (Cantor)
List of RIMAsEdit
Naturally occurring RIMAs in plants
- Cristancho, Mario. "Atypical Depression in the 21st Century: Diagnostic and Treatment Issues". Psychiatric Times. Archived from the original on 2 December 2013. Retrieved 23 November 2013.
- Isbister, Geoffrey K., et al. "Moclobemide poisoning: toxicokinetics and occurrence of serotonin toxicity." British journal of clinical pharmacology 56.4 (2003): 441-450
- Kato T, Dong B, Ishii K, Kinemuchi H (1986) Brain dialysis: in vivo metabolism of dopamine and serotonin by monoamine oxidase A but not B in the striatum of unrestrained rats. J Neurochem 46:1277–1282
- Grady, Meghan M.; Stahl, Stephen M. (2012). "Practical guide for prescribing MAOIs: debunking myths and removing barriers". CNS Spectrums. 17: 17, pp 2–10. doi:10.1017/S109285291200003X. Archived from the original on 7 July 2017.
- McCabe-Sellers, Beverly J.; Staggs, Cathleen G.; Bogle, Margaret L. (2006). "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: S58–S65. doi:10.1016/j.jfca.2005.12.008. Archived from the original on 8 April 2013.
- "Depression (major depressive disorder) - Symptoms and causes". mayoclinic.com. Archived from the original on 29 October 2013. Retrieved 1 May 2018.
- Liebowitz, M. R.; Hollander, E.; Schneier, F.; Campeas, R.; Welkowitz, L.; Hatterer, J.; Fallon, B. (1990). "Reversible and irreversible monoamine oxidase inhibitors in other psychiatric disorders". Acta Psychiatrica Scandinavica. 82 (S360): 29–34. doi:10.1111/j.1600-0447.1990.tb05321.x. PMID 2248064.
- Buigues, J; Vallejo, J (1987). "Therapeutic response to phenelzine in patients with panic disorder and agoraphobia with panic attacks". The Journal of Clinical Psychiatry. 48 (2): 55–9. PMID 3542985.
- Liebowitz, Michael R.; Schneier, Frank; Campeas, Raphael; Hollander, Eric; Hatterer, Julie; Fyer, Abby; Gorman, Jack; Papp, Laslo; Davies, Sharon; Gully, Robert; Klein, Donald F. (1992). "Phenelzine vs Atenolol in Social Phobia". Archives of General Psychiatry. 49 (4): 290–300. doi:10.1001/archpsyc.49.4.290. PMID 1558463.
- Versiani, M.; Nardi, A. E.; Mundim, F. D.; Alves, A. B.; Liebowitz, M. R.; Amrein, R. (1992). "Pharmacotherapy of social phobia. A controlled study with moclobemide and phenelzine". The British Journal of Psychiatry. 161 (3): 353–60. doi:10.1192/bjp.161.3.353. PMID 1393304.
- Heimberg, Richard G.; Liebowitz, Michael R.; Hope, Debra A.; Schneier, Franklin R.; Holt, Craig S.; Welkowitz, Lawrence A.; Juster, Harlan R.; Campeas, Raphael; Bruch, Monroe A.; Cloitre, Marylene; Fallon, Brian; Klein, Donald F. (1998). "Cognitive Behavioral Group Therapy vs Phenelzine Therapy for Social Phobia". Archives of General Psychiatry. 55 (12): 1133–41. CiteSeerX . doi:10.1001/archpsyc.55.12.1133. PMID 9862558.
- Jarrett, RB; Schaffer, M; McIntire, D; Witt-Browder, A; Kraft, D; Risser, RC (1999). "Treatment of atypical depression with cognitive therapy or phenelzine: A double-blind, placebo-controlled trial". Arch Gen Psychiatry. 56 (5): 431–7. doi:10.1001/archpsyc.56.5.431. PMC . PMID 10232298.
- Liebowitz, Michael R.; Quitkin, Frederic M.; Stewart, Jonathan W.; McGrath, Patrick J.; Harrison, Wilma; Rabkin, Judith; Tricamo, Elaine; Markowitz, Jeffrey S.; Klein, Donald F. (1984). "Phenelzine v imipramine in atypical depression. A preliminary report". Archives of General Psychiatry. 41 (7): 669–77. doi:10.1001/archpsyc.1984.01790180039005. PMID 6375621.
- Walsh, B; Stewart, JW; Roose, SP; Gladis, M; Glassman, AH (1984). "Treatment of bulimia with phenelzine: A double-blind, placebo-controlled study". Arch Gen Psychiatry. 41 (11): 1105–9. doi:10.1001/archpsyc.1983.01790220095015. PMID 6388524.
- Rothschild, Rachel; Quitkin, H. Matthew; Quitkin, Frederic M.; Stewart, Jonathan W.; Ocepek-Welikson, Katja; McGrath, Patrick J.; Tricamo, Elaine (1994). "A double-blind placebo-controlled comparison of phenelzine and imipramine in the treatment of bulimia in atypical depressives". International Journal of Eating Disorders. 15 (1): 1–9. doi:10.1002/1098-108X(199401)15:1<1::AID-EAT2260150102>3.0.CO;2-E. PMID 8124322.
- Walsh, B.Timothy; Stewart, Jonathan W.; Roose, Steven P.; Gladis, Madeline; Glassman, Alexander H. (1985). "A double-blind trial of phenelzine in bulimia". Journal of Psychiatric Research. 19 (2–3): 485–9. doi:10.1016/0022-3956(85)90058-5. PMID 3900362.
- Walsh, B; Gladis, M; Roose, SP; Stewart, JW; Stetner, F; Glassman, AH (May 1988). "Phenelzine vs placebo in 50 patients with bulimia". Arch Gen Psychiatry. 45 (5): 471–5. doi:10.1001/archpsyc.1988.01800290091011. PMID 3282482.
- Davidson, J; Ingram, J; Kilts, C (1987). "A pilot study of phenelzine in the treatment of post-traumatic stress disorder". The British Journal of Psychiatry. 150 (2): 252–5. doi:10.1192/bjp.150.2.252.
- Soloff, PH; Cornelius, J; George, A; Nathan, S; Perel, JM; Ulrich, RF (1993). "Efficacy of phenelzine and haloperidol in borderline personality disorder". Arch Gen Psychiatry. 50 (5): 377–85. doi:10.1001/archpsyc.1993.01820170055007. PMID 8489326.
- Mallinger, Alan G.; Frank, Ellen; Thase, Michael E.; Barwell, Michelle M.; Diazgranados, Nancy; Luckenbaugh, David A.; Kupfer, David J. (2009). "Revisiting the effectiveness of standard antidepressants in bipolar disorder: are monoamine oxidase inhibitors superior?". Psychopharmacology Bulletin. 42 (2): 64–74. PMC . PMID 19629023.
- http://www.psycom.net/hysteroid.html Dowson, JH (1987). "MAO inhibitors in mental disease: their current status. [Review]". Journal of Neural Transmission. Supplementum. 23: 121–38. PMID 3295114.
- Mosher, Clayton James, and Scott Akins. Drugs and Drug Policy : The Control of Consciousness Alteration. Thousand Oaks, Calif.: Sage, 2007.[page needed]
- Stahl, Stephen (2011). Case Studies: Stahl's Essential Psychopharmacology.
- Lotufo-Neto F, Trivedi M, Thase ME (March 1999). "Meta-analysis of the reversible inhibitors of monoamine oxidase type A moclobemide and brofaromine for the treatment of depression". Neuropsychopharmacology. 20 (3): 226–47. doi:10.1016/S0893-133X(98)00075-X. PMID 10063483.
- FDA. "EMSAM Medication Guide" (PDF). Archived (PDF) from the original on 10 October 2015.
- Lavian, Gila; Finberg, John P.; Youdim, Moussa B. (1993). "The advent of a new generation of monoamine oxidase inhibitor antidepressants: pharmacologic studies with moclobemide and brofaromine". Clinical Neuropharmacology. 16 (Suppl 2): S1–7. PMID 8313392.
- Boyer, Edward W.; Shannon, Michael (2005). "The Serotonin Syndrome". New England Journal of Medicine. 352 (11): 1112–20. doi:10.1056/NEJMra041867. PMID 15784664.
- Pharmacology from H.P. Rang, M.M. Dale, J.M. Ritter, P.K. Moore, year 2003, chapter 38
- "MHRA PAR Dextromethorphan hydrobromide, p. 12" (PDF). Archived (PDF) from the original on 10 May 2017.
- 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.
- Fowler, J. S.; Volkow, N. D.; Wang, G. J.; Pappas, N.; Logan, J.; Shea, C.; Alexoff, D.; MacGregor, R. R.; Schlyer, D. J.; Zezulkova, I.; Wolf, A. P. (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. Bibcode:1996PNAS...9314065F. doi:10.1073/pnas.93.24.14065. PMC . PMID 8943061.
- Fowler, J. S.; Volkow, N. D.; Wang, G-J.; Pappas, N.; Logan, J.; MacGregor, R. R.; Alexoff, D.; Shea, C.; Schlyer, D. J.; Wolf, A. P.; Warner, D.; Zezulkova, I.; Cilento, R. (1996). "Inhibition of monoamine oxidase B in the brains of smokers". Nature. 379 (6567): 733–736. Bibcode:1996Natur.379..733F. doi:10.1038/379733a0. ISSN 0028-0836. PMID 8602220.
- 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.
- Dobson, Keith S.; 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 . PMID 18540740.
- "Active ingredient: Amphetamine – Brands, Medical Use, Clinical Data". DrugLib.com. Archived from the original on 21 September 2013. Retrieved 26 May 2013.
- Hammerness, Paul; Parada, Hector; Abrams, Annah (2002). "Linezolid: MAOI Activity and Potential Drug Interactions". Psychosomatics. 43 (3): 248–9. doi:10.1176/appi.psy.43.3.248-a. PMID 12075044.
- Fowler, J. S.; Logan, J; Azzaro, A. J.; Fielding, R. M.; Zhu, W; Poshusta, A. K.; Burch, D; Brand, B; Free, J; Asgharnejad, M; Wang, G. J.; Telang, F; Hubbard, B; Jayne, M; King, P; Carter, P; Carter, S; Xu, Y; Shea, C; Muench, L; Alexoff, D; Shumay, E; Schueller, M; Warner, D; Apelskog-Torres, K (2009). "Reversible Inhibitors of Monoamine Oxidase-A (RIMAs): Robust, Reversible Inhibition of Human Brain MAO-A by CX157". Neuropsychopharmacology. 35 (3): 623–631. doi:10.1038/npp.2009.167. PMC . PMID 19890267.
- Edward J. Massaro (2002). Handbook of Neurotoxicology. ISBN 9780896037960.
- Nowakowska, Elżbieta; Chodera, Alfons (1997). "Inhibitory monoaminooksydazy nowej generacji" [New generation of monoaminooxidase inhibitors]. Polski Merkuriusz Lekarski (in Polish). 3 (13): 1–4. PMID 9432289.
- Edmondson, D. E.; Binda, C; Mattevi, A (2007). "Structural insights into the mechanism of amine oxidation by monoamine oxidases A and B". Archives of Biochemistry and Biophysics. 464 (2): 269–276. doi:10.1016/j.abb.2007.05.006. PMC . PMID 17573034.
- "FDA Approves Emsam (Selegiline) as First Drug Patch for Depression" (Press release). U.S. Food and Drug Administration. 28 February 2006. Archived from the original on 21 November 2009. Retrieved 19 November 2009.
- BLTC Research (2006). "Rasagiline: a neuroprotective smart drug?". The Good Drug Guide. Archived from the original on 9 December 2007. Retrieved 2 December 2007.
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 food. Thus, low-dosage rasagiline demands no special dietary restrictions.
- Ramachandraih C, Subramanyam N, Bar K, Baker G, Yeragani V (Apr–June 2011). "Antidepressants: From MAOIs to SSRIs and more". Indian J Psychiatry. 53 (2): 180–182. doi:10.4103/0019-5545.82567. PMC . PMID 21772661. Check date values in:
- Shulman, Kenneth I.; Herrmann, Nathan; Walker, Scott E. (2013). "Current Place of Monoamine Oxidase Inhibitors in the Treatment of Depression". CNS Drugs. 27 (10): 789–97. doi:10.1007/s40263-013-0097-3. PMID 23934742.
- 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.
- 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 . PMID 7905288.
- Baldwin D, Rudge S (1993). "Moclobemide: a reversible inhibitor of monoamine oxidase type A". Br J Hosp Med. 49 (7): 497–9. PMID 8490690.
- Lawrence KR, Adra M, Gillman PK (June 2006). "Serotonin toxicity associated with the use of linezolid: a review of postmarketing data". Clinical Infectious Diseases. 42 (11): 1578–83. doi:10.1086/503839. ISSN 1058-4838. PMID 16652315.
- Petzer, A; Harvey, B. H.; Wegener, G; Petzer, J. P. (2012). "Azure B, a metabolite of methylene blue, is a high-potency, reversible inhibitor of monoamine oxidase". Toxicol. Appl. Pharmacol. 258 (3): 403–9. doi:10.1016/j.taap.2011.12.005. PMID 22197611.
- Donskaya, N.S.; Antonkina, O.A.; Glukhan, E. N.; Smirnov, S. K. (1 July 2004). "Antidepressant Befol Synthesized Via Interaction of 4-Chloro-N-(3-chloropropyl)benzamide with Morpholine". Pharmaceutical Chemistry Journal. 0091-150X. Kluwer Academic Publishers-Plenum Publishers. 38 (7): 381–384. doi:10.1023/B:PHAC.0000048439.38383.5f.
- Kulkarni, SK; Bhutani, AK; Bishnoi, M. (3 September 2008). "Antidepressant activity of curcumin: involvement of serotonin and dopamine system". Psychopharmacology. 201 (3): 435–442. doi:10.1007/s00213-008-1300-y. PMID 18766332. Archived from the original on 31 March 2017
- Kulkarni, S. K.; Dhir, A. (March 2010). "An Overview of Curcumin in Neurological Disorders". Indian Journal of Pharmaceutical Sciences. 72 (2): 149–154. doi:10.4103/0250-474X.65012. PMC . PMID 20838516.
- "Curcumin and the MAO Inhibitor "Cheese Effect" from Tyramine Triggered Hypertension". EmediaHealth. 17 January 2012. Archived from the original on 30 March 2017. Retrieved 28 March 2017.