Pharmacological actions of benidipine hydrochloride in several isolated smooth muscles and myocardium.
Using various isolated smooth muscles and myocardium, the calcium antagonistic effect of (+/-)-(R*)-2,6-dimethyl-4-(m-nitrophenyl)- 1,4-dihydropyridine-3,5-dicarboxylic acid (R*)-1-benzyl-3-piperidinyl ester, methyl ester hydrochloride (benidipine hydrochloride, KW-3049), and its specificity were examined. Furthermore, the in vitro duration of action and the antispasmodic actions in coronary arteries were investigated in comparison with those of nifedipine, verapamil and diltiazem. 1. Ca antagonisms of KW-3049 When the Ca antagonistic effect of KW-3049 was investigated, for which the contractile responses to KCl in isolated mesenteric arteries in rabbits were taken as an indicator, the activity of KW-3049 was of about the same degree as nifedipine and approx. 30 times greater than those of verapamil and diltiazem. On the other hand, the negative inotropic action in isolated atria in rabbits was weaker than that of nifedipine. 2. Influences on responses to various agonists From the investigations using various isolated organs, it was evident that KW-3049 had neither agonistic nor antagonistic actions or very weak actions on the following receptors: alpha 1, alpha 2, beta 1, beta 2, H1, H2, muscarinic acetylcholine, 5HT2, angiotensin II, and prostaglandin F2 alpha. 3. Duration of in vitro actions Inhibitory actions of KW-3049 on 55 mmol/l-induced contractions in isolated mesenteric arteries in rabbits persisted even 180 min after the removal of drug solution and the repeated wash-out of tissues. On the other hand, those of nifedipine, verapamil and diltiazem disappeared within 60 to 120 min.(ABSTRACT TRUNCATED AT 250 WORDS)
Karasawa
A
A
Pharmaceutical Research Laboratories, Kyowa Hakko Kogyo Co., Ltd., Shizuoka, Japan.
Kubo
K
K
Shuto
K
K
Oka
T
T
Nakamizo
N
N
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003331:Coronary Vessels / Q000187:drug effects; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects; D015394:Molecular Structure; D009130:Muscle, Smooth / Q000187:drug effects*; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains
D002121:Calcium Channel Blockers; C050883:benidipine hydrochloride; D009543:Nifedipine