THE PHARMACOLOGY AND MODE OF ACTION OF VENLAFAXINE

Venlafaxine is an antidepressant with a unique pharmacological profile . It has two primary sites of action, inhibiting the presynaptic reupt ake transporter molecules for both serotonin and norepinephrine. It ha s its most potent effect on serotonin uptake, with norepinephrine reup take inhibition being approximately one third that of its inhibitory e ffect upon serotonin uptake. The inhibition of these two amine reuptak e systems appears to account for the pharmacological activity of venla faxine in neurophysiological and behavioural models sensitive to antid epressants, and presumably also for its clinical antidepressant activi ty. Both mechanisms appear to be active within a pharmacologically rel evant dose range. Venlafaxine has no affinity for adrenergic, choliner gic, or histaminergic neuroreceptors and so would be expected to have an improved adverse event and tolerability profile compared to the tri cyclic antidepressants. O-desmethylvenlaiaxine, the major metabolite i n humans, has a pharmacological profile similar to that of the parent drug, so that the pharmacological selectivity of venlafaxine is preser ved after its metabolism. Expected clinical advantages resulting from venlafaxine's dual mechanism of action would include a positive dose-r esponse curve and a relatively rapid onset of action.