Metazosin

Metazosin (KENOSIN) displaces 3H-prazosin from its bond to alpha-1 receptors of the cerebral cortex, antagonizes the effects of phenylephrin on spinal rats and on perfused peripheral vascular regions, which demonstrates that it is a blocker of alpha-1 adrenergic receptors. It does not affect the central alpha-2 adrenergic receptors. No peripheral antiserotonin effect was found. Metazosin decreases the blood pressure in normotensive and hypertensive animals. On intravenous administration, the decrease commences very rapidly after the onset of administration. In dogs, systolic and diastolic blood pressure, cardiac output, peripheral resistance and pressure in the pulmonary artery are decreased. In animals with experimentally increased pressure in the lesser circulation it produces a decrease in pressure. On the basis of hypotensively active doses in experimental animals, the administration of 5 mg was proposed as the clinica pose. Results of the 1st stage of clinical trials have demonstrated that this dose is effective in persons with the systolic pressure higher than 120 mm Hg. At present the effect of metazosin is tested on hypertonic patients.

Based on pharmacokinetic data from mice, rats, and rabbits the prediction of pharmacokinetics of intravenous metazosin in man has been performed. The correlations were based upon allometric scaling of plasma clearance and the volume of distribution at steady‐state. A one‐compartment body model approximating clinical pharmacokinetics fits well the elimination phase of subsequently measured metazosin concentrations in volunteers. Fitting human pharmacokinetic data to allometric equations enabled us to superimpose pharmacokinetic curves from different species.