Pharmacodynamics of S-2150, a simultaneous calcium-blocking and alpha(1)-inhibiting antihypertensive drug, in rats

The in-vivo pharmacodynamics of S-2150, a newly developed dual-blocking typ e antihypertensive drug, was evaluated following intravenous infusion to ra ts. Previous in-vitro studies showed that the drug has two distinct mechani sms of antihypertensive effect-calcium-channel blocking activity and alpha( 1)-adrenoceptor antagonism-which could be explained by a combination of two different pharmacodynamic models. The present in-vivo study showed that S-2150 also displays a complex pharma codynamic profile (as measured by the decrease in mean blood pressure), whi ch could be described by a combination of two sigmoid E-max models independ ently connected with the central compartment and the effect compartment. These results suggested that the dual-blocking mechanism of S-2150, which h as been observed in in-vitro experiments, was also evaluated by the pharmac odynamic analysis of in-vivo experimental data.