indication

For the treatment of depression.

pharmacology

Moclobemide belongs to a class of MAOI antidepressants known as reversible inhibitors of monoamine oxidase type-A (RIMAs). The primary role of monoamine oxidase MAO lies in the metabolism of and regulation of the levels of monoamines (serotonin, norepinephrine, and dopamine). Within neurons, MAO appears to regulate the levels of monoamines released upon synaptic firing. Since depression is associated with low levels of monoamines, the inhibition of MAO serves to ease depressive symptoms. RIMAs demonstrate transient inhibition of the substrate binding site of MAO-A as well as competitive displacement from this site by bioamines. The RIMAs are distinguished from the older monoamine oxidase inhibitors (MAOIs) by their selectivity and reversibility.

mechanism of action

The mechanism of action of moclobemide involves the selective, reversible inhibition of MAO-A. This inhibition leads to a decrease in the metabolism and destruction of monoamines in the neurotransmitters. This results in an increase in the monoamines, relieving depressive symptoms.

toxicity

LD50 (mouse) is 730mg/kg and LD50 (rat) is 1,300mg/kg. Signs of toxicity include hypertension, drowsiness, dizziness, confusion, tremors, headache, agitation, muscle rigidity and seizures.

biotransformation

Moclobemide is almost completely metabolized in the liver by Cytochrome P450 2C19 and 2D6.

absorption

Well absorbed from the gastrointestinal tract (> 95%). The presence of food reduces the rate but not the extent of absorption. Hepatic first pass metabolism reduces bioavailability to 45-70% following administration of a single dose, but increases to 80% with multiple dosing as a result of saturation of the first pass effect. Peak plasma concentrations are reached within 1 - 2 hours following oral administration.

half life

1-2 hours (4 hours in cirrhotic patients); metabolites are renally excreted

drug interactions

Amitriptyline: Possible severe adverse reaction with this combination

Amoxapine: Possible severe adverse reaction with this combination

Bezafibrate: MAO Inhibitors may enhance the adverse/toxic effect of Bezafibrate. Avoid concomitant use of bezafibrate with monoamine oxidase inhibitors (MAOIs) like moclobemide.

Brimonidine: MAO Inhibitors like moclobemide may enhance the hypertensive effect of Alpha2-Agonists (Ophthalmic). The concomitant use of monoamine oxidase inhibitors and ophthalmic alpha2 agonists is contraindicated.

Buprenorphine: Buprenorphine may enhance the adverse/toxic effect of MAO Inhibitors like moclobemide. When possible, avoid use of buprenorphine in patients who have used a monoamine oxidase inhibitor within the past 14 days due to possible severe adverse effects.

Cimetidine: Cimetidine may increase the serum concentration of moclobemide by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of moclobemide if cimetidine is initiated, discontinued or dose changed.

Citalopram: Possible serotoninergic syndrome

Clomipramine: Possible severe adverse reaction with this combination

Desipramine: Possible severe adverse reaction with this combination

Desvenlafaxine: Increased risk of serotonin syndrome. Ensure adequate washout period between therapies to avoid toxicity. Concurrent therapy should be avoided.

Dextromethorphan: Increased CNS toxicity

Dobutamine: Moclobemide increases the sympathomimetic effect of dobutamine.

Donepezil: Possible antagonism of action

Dopamine: Moclobemide increases the sympathomimetic effect of dopamine.

Doxepin: Possible severe adverse reaction with this combination

Ephedra: Moclobemide increases the sympathomimetic effect of ephedra.

Ephedrine: Moclobemide increases the sympathomimetic effect of ephedrine.

Epinephrine: Moclobemide increases the sympathomimetic effect of epinephrine.

Fenoterol: Moclobemide increases the sympathomimetic effect of fenoterol.

Fluoxetine: Risk of serotoninergic syndrome

Fluvoxamine: Increased incidence of adverse effects with this association

Galantamine: Possible antagonism of action

Imipramine: Possible severe adverse reaction with this combination

Isoproterenol: Moclobemide increases the sympathomimetic effect of isoproterenol.

Meperidine: Increased CNS toxicity (can cause death)

Mephentermine: Moclobemide increases the sympathomimetic effect of mephentermine.

Metaraminol: Moclobemide increases the sympathomimetic effect of metaraminol.

Methoxamine: Moclobemide increases the sympathomimetic effect of methoxamine.

Norepinephrine: Moclobemide increases the sympathomimetic effect of norepinephrine.

Nortriptyline: Possible severe adverse reaction with this combination

Orciprenaline: Moclobemide increases the sympathomimetic effect of orciprenaline.

Paroxetine: Possible severe adverse reaction with this combination

Phenylephrine: Moclobemide increases the sympathomimetic effect of phenylephrine.

Phenylpropanolamine: Moclobemide increases the sympathomimetic effect of phenylpropanolamine.

Pirbuterol: Moclobemide increases the sympathomimetic effect of pirbuterol.

Procaterol: Moclobemide increases the sympathomimetic effect of procaterol.

Protriptyline: Possible severe adverse reaction with this combination

Pseudoephedrine: Moclobemide increases the sympathomimetic effect of pseudoephedrine.

Rivastigmine: Possible antagonism of action

Rizatriptan: The MAO inhibitor, moclobemide, may decrease the metabolism and clearance of the serotonin 5-HT receptor agonist, rizatriptan. Concomitant therapy is contraindicated.

Salbutamol: Moclobemide increases the sympathomimetic effect of salbutamol.

Selegiline: Decrease in selectivity

Sertraline: Possible severe adverse reaction with this combination

Sibutramine: Possible serotoninergic syndrome with this combination

Tacrine: The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Moclobemide, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.

Terbinafine: Terbinafine may reduce the metabolism and clearance of Moclobemide. Consider alternate therapy or monitor for therapeutic/adverse effects of Moclobemide if Terbinafine is initiated, discontinued or dose changed.

Terbutaline: Moclobemide increases the sympathomimetic effect of terbutaline.

Tetrabenazine: Tetrabenazine may increase the adverse/toxic effects of Moclobemide. Concomitant therapy is contraindicated.

Ticlopidine: Ticlopidine may decrease the metabolism and clearance of Moclobemide. Consider alternate therapy or monitor for adverse/toxic effects of Moclobemide if Ticlopidine is initiated, discontinued or dose changed.

Tolcapone: Tolcapone and Moclobemide decrease the metabolism of endogenous catecholamines. Concomitant therapy may result in increased catecholamine effects. Consider alternate therapy or use cautiously and monitor for increased catecholamine effects.

Tramadol: Tramadol may increase the risk of serotonin syndrome and seizure induction by the MAO inhibitor, moclobemide.

Tranylcypromine: Increased risk of serotonin syndrome. Use caution during concomitant therapy and monitor for symptoms of serotonin syndrome.

Trazodone: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Trimethobenzamide: Trimethobenzamide and Moclobemide, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Monitor for enhanced anticholinergic effects.

Trimipramine: Increased risk of serotonin syndrome. Ensure adequate washout period between therapies to avoid toxicity. Avoid combination or monitor for symptoms of serotonin syndrome and/or hypertensive crisis.

Triprolidine: Triprolidine and Moclobemide, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Additive CNS depressant effects may also occur. Monitor for enhanced anticholinergic and CNS depressant effects.

Trospium: Trospium and Moclobemide, two anticholinergics, may cause additive anticholinergic effects and enhanced adverse/toxic effects. Monitor for enhanced anticholinergic effects.

Tryptophanyl-5'amp: Possible severe adverse reaction with this combination

Venlafaxine: Increased risk of serotonin syndrome. Ensure adequate washout period between therapies to avoid toxicity. Concurrent therapy should be avoided.

Zolmitriptan: The MAO inhibitor, moclobemide, may increase the serum concentration of zolmitriptan by decreasing its metabolism. Concomitant therapy and use of zolmitriptan within two weeks of discontinuing moclobemide are contraindicated.