Aurorix Mechanism of Action

Pharmacology: Pharmacodynamics: Mechanism of Action: Moclobemide is an antidepressant which affects the monoaminergic cerebral neurotransmitter system by means of a reversible inhibition of monoamine oxidase preferentially of type A (RMAO-A). The metabolism of noradrenaline, dopamine and serotonin is decreased by this effect, and this leads to increase extracellular concentrations of these neuronal transmitters.
As a result of its elevating effect on mood and psychomotor activity, moclobemide relieves symptoms such as dysphoria, exhaustion, lack of drive and inability to concentrate. These effects most often appear within the first week of therapy. Moclobemide also relieves symptoms related to social phobia.
Though moclobemide has no sedative properties, it improves the quality of sleep in most depressive patients within days. Moclobemide does not impair alertness.
Clinical/Efficacy Studies: Short-term and long-term animal studies indicate low toxicity. No cardiac toxicity has been observed.
Pharmacokinetics: Absorption: After oral administration, moclobemide is completely absorbed from the gastrointestinal tract into the portal blood. Peak plasma concentrations of the drug are usually reached within one hour of administration. A hepatic first-pass effect reduces the systemically available dose fraction (bioavailability). However, saturation of these metabolic pathways during the first week of dosing (300-600 mg/day) results in essentially complete oral bioavailability thereafter. Plasma concentrations following multiple doses of moclobemide increase over the first week of therapy and then stabilize. When the daily dose is increased, there is a greater-than-proportional increase in steady-state concentrations.
Distribution: Due to its lipophilic nature, moclobemide is extensively distributed in the body. The volume of distribution (V_ss) is about 1.0 l/kg. Binding of the drug to plasma proteins, mainly albumin, is low (50%). Insignificant amounts are excreted in human breast milk.
Metabolism/Biotransformation: The drug is almost entirely metabolised before its elimination from the body. Metabolism occurs largely via oxidative reactions on the morphine/morpholine moiety of the molecule. Degradation products with pharmacological activity are present in the systemic circulation in man at very low concentrations only. The major metabolites present in plasma are a lactam derivative and an N-oxide derivative. Moclobemide has been shown to be metabolised in part by the polymorphic isoenzymes CYP2C19 and CYP2D6. Thus, in genetically or drug-induced (via metabolic inhibitors) poor metabolisers, metabolism of the drug may be affected. Two studies conducted to investigate the magnitude of these effects suggested that, due to the presence of multiple alternative metabolic pathways, they are of no clinical significance and should not necessitate dosage modification.
Elimination: Moclobemide is rapidly eliminated by metabolic processes. Total clearance is approximately 20-50 l/hour. The mean elimination half-life during multiple dosing (300 mg b.i.d) is approximately 3 hours and generally ranges from 2-4 hours in most patients. Less than 1% of a dose is excreted renally in unchanged form. The metabolites formed are eliminated renally. Insignificant amounts are secreted in human breast milk.
Pharmacokinetics in special populations: Elderly: Absorption and disposition parameters are unchanged in the elderly.
Patients with renal impairment: Renal disease does not alter the elimination characteristics of moclobemide.
Patients with hepatic impairment: In advanced liver insufficiency, the metabolism of moclobemide is reduced (see Special Dosage Instructions under Dosage & Administration).