Moclobemide, sold under the brand names Amira, Aurorix,[8] Clobemix, Depnil and Manerix[9] among others, is a reversible inhibitor of monoamine oxidase A (RIMA) drug primarily used to treat depression and social anxiety.

Initially, Aurorix was also marketed by Roche in South Africa, but was withdrawn after its patent rights expired and Cipla Medpro's Depnil and Pharma Dynamic's Clorix became available at half the cost.

No significant rise in blood pressure occurs when moclobemide is combined with amines such as tyramine-containing foods or pressor amine drugs, unlike with the older irreversible and non-selective monoamine oxidase inhibitors (MAOIs), which cause a severe rise in blood pressure with such combination.

[17] MAOIs such as moclobemide are reported to have a relatively fast onset of action compared to other antidepressant drug classes,[18] and have good long-term tolerability in terms of side effects.

[19] Tolerance does not seem to occur; research has found that moclobemide retains its beneficial therapeutic properties in depression for at least a year.

[11][12] Reversible MAOIs such as moclobemide may have advantages in the treatment of depression associated with Alzheimer's disease due to its effect on noradrenaline.

[25] Due to its superior safety profile, moclobemide has been recommended as a first line agent for the treatment of depression in the elderly.

[61] Other side effects include nausea, insomnia, tremor and lightheadedness; orthostatic hypotension (dizziness upon standing) is uncommon even among the elderly.

The following are the potential adverse effects and their respective incidences:[14][71] Avoid use in:[11] and caution is recommended in:[12] Moclobemide has fewer interactions than irreversible MAOIs.

[85] Irreversible MAOIs can cause unpleasant and occasionally dangerous side effects such as a hypertensive crises after intake of food or drink containing indirectly acting sympathomimetic amines such as tyramine.

[86] Of 2300 people in multiple clinical trials who were treated with moclobemide in doses up to 600 mg with no dietary restrictions, none experienced a tyramine-mediated hypertensive reaction.

[58] As the pressor effect of moclobemide is so low, dietary restrictions are not necessary in people eating a normal diet, in contrast to irreversible MAOIs.

[89] While moclobemide or the irreversible MAO-B selective inhibitor selegiline taken alone has very little pressor effect, and requires no dietary restriction, the combination of selegiline with moclobemide leads to a significant enhancement of the pressor effect and such a combination requires dietary restriction of foods containing high amounts of tyramine.

[92] Intoxications with moclobemide as single agent are usually mild; however, when combined with tricyclic or SSRI antidepressants the overdose is much more toxic and potentially fatal.

[95] Patients with mixed intoxications (e.g. with other CNS active drugs) may show severe or life-threatening symptoms and should be hospitalized.

Withdrawal symptoms appear to be very rare with moclobemide compared to other antidepressants[citation needed]; a single report of relatively mild flu-like symptoms persisting for 7 days after rapid reduction of high dose moclobemide therapy has been reported in one patient.

[97] Discontinuation of moclobemide is recommended to be done gradually to minimise side effects (e.g. rapid return of condition being treated and/or the appearance of withdrawal symptoms).

Tolerance to the therapeutic effects has been reported in a small number of users of MAOIs including moclobemide.

[17] Moclobemide is a benzamide,[13] derivative of morpholine,[98] which acts pharmacologically as a selective, reversible inhibitor of monoamine oxidase-A (RIMA),[10] a type of monoamine oxidase inhibitor (MAOI), and increases levels of norepinephrine (noradrenaline), dopamine, and especially serotonin[9][99] in neuronal cells as well as in synaptic vesicles; extracellular levels also increase which results in increased monoamine receptor stimulation and suppression of REM sleep, down regulation of beta-3 adrenergic receptors.

Moclobemide's primary action is to disable MAO-A enzymes from decomposing norepinephrine, serotonin, and dopamine which results in a rising level of these neurotransmitters.

[9] Single or repeated dosing with 100–300 mg of moclobemide leads to a reduction in deaminated metabolites of amines such as 3,4-dihydroxyphenylacetic acid, 3,4-dihydroxyphenylethylglycol as well as 5-HIAA.

[9][99] The inhibition of MAO-A by moclobemide is 10 times more potent than the irreversible MAOI phenelzine and approximately equivalent to tranylcypromine and isocarboxazid.

[109] Long-term treatment with moclobemide leads to an increase in cyclic adenosine monophosphate (cAMP) binding to cAMP-dependent protein kinase (PKA).

[110] Moclobemide is chemically unrelated to irreversible MAOI antidepressants and only has a very weak pressor effect of orally administered tyramine.

The pharmacodynamic action encompasses activation, elevation of mood, and improvement of symptoms like dysphoria, fatigue, and difficulties in concentration.

[5] Moclobemide has good penetration across the blood brain barrier with peak plasma levels within the central nervous system occurring 2 hours after administration.

Reversible MAOIs were developed in the hope that they would exert efficacy in depressive disorders but with less of the toxicity of the older irreversible compounds; moclobemide's discovery and marketing brought the renewed interest in MAOIs due to an absence of dangerous tyramine food interactions and potent antidepressant effects.

[127] Moclobemide as well as other newer antidepressants such as the SSRIs led to changes in prescribing patterns and broadened the treatment options for the management of depressive disorders.

[78][130] Additionally moclobemide was found, unlike most other antidepressants on the market, to actually improve all aspects of sexual function.

[9] Due to a lack of financial incentive, such as the costs of conducting the necessary trials to gain approval, moclobemide is unavailable in the USA pharmaceutical market.