MIZEST

MIZEST acts as an antagonist at central pre-synaptic alpha (2)-receptors, inhibiting negative feedback to the presynaptic nerve and causing an increase in NE release. Blockade of heteroreceptors, alpha (2)-receptors contained in serotonergic neurons, enhances the release of 5-HT, increasing the interactions between 5-HT and 5-HT1 receptors and contributing to the anxiolytic effects of MIZEST. MIZEST also acts as a weak antagonist at 5-HT1 receptors and as a potent antagonist at 5-HT2 (particularly subtypes 2A and 2C) and 5-HT3 receptors. MIZEST also exhibits significant antagonism at H1- receptors, resulting in sedation.

The absorption is rapid and complete, but, due to first-pass metabolism, absolute bioavailability is 50%. Protein binding- 85% MIZEST is extensively metabolized by demethylation and hydroxylation followed by glucuronide conjugation. Cytochrome P450 2D6 and cytochrome P450 1A2 are involved in formation of the 8-hyfroxy metabolite of MIZEST, and cytochrome P450 3A4 is responsible for the formation of the N-desmethyl and N-oxide metabolites. This drug is known to be substantially excreted by the kidney (75%). Half-life: 20- 40 hours

Usual Adult Dose for Depression Initial dose: 15 mg orally once a day at bedtime Maintenance dose: 15 to 45 mg per day Renal Dose Adjustment Use with caution in patients with renal insufficiency (CrCl< 40mL/min). Lower doses may be required. Liver Dose Adjustment Use with caution in patients with hepatic insufficiency. Lower doses may be required. Dose changes should not be made at interval of less than 1 to 2 weeks Elderly and patients with renal or hepatic impairment may require lower doses.

Available dose is 7.5/15mg tablet Each strip contains 10 tablets