Reversible inhibitors of monoamine oxidase A (RIMAs) are a class of drugs which selectively and reversibly inhibit the enzyme monoamine oxidase A (MAO-A). They are used clinically in the treatment of depression and dysthymia, though they have not gained widespread market share due to limited efficacy relative to other antidepressants. Because of their reversibility and selectivity, RIMAs are safer than the older monoamine oxidase inhibitors (MAOIs).
While safer than general MAOIs, RIMAs still have highly dangerous and sometimes fatal 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).
Warning: Many psychoactive substances that are reasonably safe to use on their own can suddenly become dangerous and even life-threatening when combined with certain other substances. The following list provides some known dangerous interactions (although it is not guaranteed to include all of them).
Always conduct independent research (e.g. Google, DuckDuckGo, PubMed) to ensure that a combination of two or more substances is safe to consume. Some of the listed interactions have been sourced from TripSit.
- 2C-T-x - MAO-B inhibitors can increase the potency and duration of phenethylamines unpredictably, which could be dangerous given the unpredictability of the 2C-T-x series
- 2C-x - MAO-B inhibitors can increase the potency and duration of phenethylamines unpredictably
- DOx - MAO-B inhibitors can increase the potency and duration of phenethylamines unpredictably
- Ketamine - MAO-B inhibitors appear to increase the potency of Ketamine. MAO-A inhbitors have some negative reports associated with the combination but there isn't much information available
- NBOMes - MAO-B inhibitors can increase the potency and duration of phenethylamines unpredictably
- Opioids - Coadministration of monoamine oxidase inhibitors (MAOIs) with certain opioids has been associated with rare reports of severe and fatal adverse reactions. There appear to be two types of interaction, an excitatory and a depressive one. Symptoms of the excitatory reaction may include agitation, headache, diaphoresis, hyperpyrexia, flushing, shivering, myoclonus, rigidity, tremor, diarrhea, hypertension, tachycardia, seizures, and coma. Death has occurred in some cases.
- Alcohol - Tyramine found in many alcoholic beverages can have dangerous reactions with MAOIs, causing an increase in blood pressure.
- MXE - MAO-B inhibitors appear to increase the potency of MXE. MAO-A inhbitors have some negative reports associated with the combination but there isn't much information available
- Amphetamines - MAO-B inhibitors can increase the potency and duration of phenethylamines unpredictably. MAO-A inhibitors with amphetamine can lead to hypertensive crises.
- aMT - aMT is an MAOI on its own. Using enzyme inhibitors can greatly reduce predictability of effects.
- Cocaine - This combination is poorly explored
- DXM - High risk of serotonin syndrome
- MDMA - MAO-B inhibitors can increase the potency and duration of phenethylamines unpredictably. MAO-A inhibitors with MDMA will lead to hypertensive crises.
- PCP - This combination is very poorly explored
List of RIMAs
Naturally occurring sources
- Syrian rue (Peganum harmala) (note that it also contains a MAO-A and MAO-B inhibitors)
- Turmeric (Curcuma longa): Curcumin (selectivity for MAO-A is disputed). Curcumin is commonly sold with piperine that enhances the effect of MAO inhibition.
For an updated list of RIMAs, see: List of RIMAs (Wikipedia)
Trade names: Apo-Moclob, Apo-Moclobemide, Auromid, Aurorix, Bei Su, Biorix, Depnil, Eutac, Hai Bei Lin, Langtian, Manerix, Mobemid, Moclamine, Moclo A, Moclobemid - 1 A Pharma, Moclobemid AL, Moclobemid HEXAL, Moclobemid ratiopharm, Moclobemida, Moclobemida Genedec, Moclobemida Teva, Moclobemide Actavis, Moclobemide Aurobindo, Moclobemide CF, Moclobemide Mylan, Moclobemide Sandoz, Moclobemide Sopharma, Moclobemide Teva, Moclobemid-neuraxpharm, Moclobemid-ratiopharm, Moclobeta, Moclod, moclodura, Moclostad, Mocrim, Modafinil Arrow, Moklar, Teva-Moclobemide, Tian Tai, Ya Zheng, and Zorix)
With moclobemide doses above 900 mg/d the risk of interaction with ingested tyramine might become clinically relevant.
- 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. (February 2010). "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. ISSN 0893-133X.
- Garcia, Eddie; Santos, Cynthia (2022). "Monoamine Oxidase Inhibitor Toxicity". StatPearls. StatPearls Publishing.
- Massaro, E. J. (2002). Handbook of Neurotoxicology. Totowa, NJ: Humana Press. p. 237. ISBN 0-89603-796-7.
- 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.
- 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.
- Tomás Herraiz; Simon D. Brandt (July–August 2014). "5-(2-Aminopropyl)indole (5-IT): a psychoactive substance used for recreational purposes is an inhibitor of human monoamine oxidase (MAO)". Drug Testing and Analysis. 6 (7–8): 607–613. doi:10.1002/dta.1530. PMID 24115740.
- Arai, Y., Toyoshima, Y., Kinemuchi, H. (1986). "Studies of Monoamine Oxidase and Semicarbazide-Sensitive Amine Oxidase II. Inhibition by α-Methylated Substrate-Analogue Monoamines, α-Methyltryptamine, α-Methylbenzylamine and Two Enantiomers of α-Methylbenzylamine". The Japanese Journal of Pharmacology. 41 (2): 191–197. doi:10.1254/jjp.41.191.
- "Moclobemide International Brands". Drugs.com. Retrieved 3 June 2017.