Pharmacodynamics of S-2150, a simultaneous calcium-blocking and alpha1-inhibiting antihypertensive drug, in rats.
The in-vivo pharmacodynamics of S-2150, a newly developed dual-blocking type antihypertensive drug, was evaluated following intravenous infusion to rats. Previous in-vitro studies showed that the drug has two distinct mechanisms of antihypertensive effect--calcium-channel blocking activity and alpha1-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 pharmacodynamic profile (as measured by the decrease in mean blood pressure), which could be described by a combination of two sigmoid Emax models independently connected with the central compartment and the effect compartment. These results suggested that the dual-blocking mechanism of S-2150, which has been observed in in-vitro experiments, was also evaluated by the pharmacodynamic analysis of in-vivo experimental data.
Ishibashi
T
T
Developmental Research Laboratories, Shionogi & Co. Ltd, Osaka, Japan. toru.ishibashi@shionogi.co.jp
Yano
Y
Y
Oguma
T
T
D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000493:pharmacokinetics; D000818:Animals; D000959:Antihypertensive Agents / Q000493:pharmacokinetics*; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D004110:Diltiazem / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D008297:Male; D008657:Metabolic Clearance Rate; D011224:Prazosin / Q000097:blood / Q000493:pharmacokinetics; D051381:Rats; D011918:Rats, Inbred SHR; D013997:Time Factors
D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; C104615:S 2150; D004110:Diltiazem; D011224:Prazosin