Cardiovascular effects of LAS 30538, a new vascular selective Ca(2+)-channel blocker.

Abstract	A new compound, 1-[2-(2,6-dimethylphenoxy)ethyl]-alpha,alpha-bis-(p-fluorphenyl)-4 -piperidine methanol (LAS 30538), was found to have potent vasodilator effects. Its vasorelaxant activity was demonstrated in rat perfused hindlimbs contracted with 80 mM K+, having an IC50 value of 40 nM. In conscious spontaneously hypertensive rats, LAS 30538 administered orally, caused dose-dependent sustained falls in systolic blood pressure with an ED30 value of 11 mg kg-1. In pithed rats, LAS 30538, strongly inhibited vasoconstriction induced by the alpha 2-adrenoceptor agonist B-HT 933 and the calcium agonist compound Bay K8644 with ED50 values of 4 mg kg-1 p.o. and 1.3 mg kg-1 i.v., respectively. Results from electrophysiological studies carried out using guinea-pig papillary muscles partially depolarized by 22 mM K+ are consistent with LAS 30538 acting as a Ca(2+)-channel blocker. When compared with verapamil, in guinea-pig and rabbit isolated heart preparations, LAS 30538 caused less cardiodepression and bradycardia. The results suggest that LAS 30538 may have some advantages over other Ca(2+)-channel blockers such as verapamil in causing less myocardial depression for a given level of vasodilatation.
Authors	I Cardelús, J Bou, J Llenas, P Berga, R W Gristwood
Journal	The Journal of pharmacy and pharmacology (J Pharm Pharmacol) Vol. 44 Issue 10 Pg. 830-5 (Oct 1992) ISSN: 0022-3573 [Print] England
PMID	1360509 (Publication Type: Comparative Study, Journal Article)
Chemical References	Calcium Channel Blockers Piperidines Vasoconstrictor Agents Vasodilator Agents LAS 30538 Verapamil Diltiazem Flunarizine
Topics	Animals Blood Pressure (drug effects) Calcium Channel Blockers (pharmacology) Diltiazem (pharmacology) Electrophysiology Flunarizine (pharmacology) Guinea Pigs Heart (drug effects) In Vitro Techniques Male Muscle, Smooth, Vascular (drug effects) Papillary Muscles (drug effects) Perfusion Piperidines (pharmacology) Rabbits Rats Rats, Inbred SHR Rats, Wistar Vasoconstrictor Agents (pharmacology) Vasodilator Agents (pharmacology) Verapamil (pharmacology)

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