Effects of benidipine hydrochloride on atrioventricular conduction time and postural reflex in gallamine-immobilized cats.
Using gallamine-immobilized cats, the effect of (+/-)-(R*)-2,6-dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-3,5-dic arb oxylic acid (R*)-1-benzyl-3-piperidinyl ester, methyl ester hydrochloride (benidipine hydrochloride, KW-3049) was compared with those of other drugs in terms of the propensity for atrioventricular conduction disturbances and orthostatic hypotension. The administration of KW-3049 at doses of 1 to 300 micrograms/kg i.v. dose-dependently lowered the blood pressure and also reduced the heart rate. In terms of the maximum blood pressure lowering activity, KW-3049 was similar in degree to nifedipine and approximately 30 times as potent as diltiazem, verapamil and phenoxybenzamine. KW-3049 as well as nifedipine, at doses with which the mean blood pressure can be reduced by 50 mmHg, hardly affected the PR-interval of ECG, whereas diltiazem and verapamil at their hypotensive doses markedly prolonged the PR interval. These four calcium antagonists at their high doses elicited 2nd or 3rd degree atrioventricular blocks in some cases. On the other hand, phenoxybenzamine did not affect the atrioventricular conduction at its hypotensive doses. Inhibitory action on the pressor responses to head-up tilting in cats was observed neither in KW-3049, nifedipine, verapamil nor diltiazem. On the contrary, phenoxybenzamine strongly inhibited the orthostatic pressor reflexes. From these results, it was suggested that in terms of the prolongation action of atrioventricular conduction KW-3049 is less potent than diltiazem and verapamil but similar in degree to nifedipine, and that KW-3049 is not likely to cause orthostatic hypotension.
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; D000959:Antihypertensive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001283:Atrioventricular Node / Q000187:drug effects* / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D002415:Cats; D004110:Diltiazem / Q000494:pharmacology / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005703:Gallamine Triethiodide; D006329:Heart Conduction System / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D007024:Hypotension, Orthostatic / Q000139:chemically induced*; D007103:Immobilization; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D010643:Phenoxybenzamine / Q000494:pharmacology / Q000627:therapeutic use; D011187:Posture; D014700:Verapamil / Q000494:pharmacology / Q000627:therapeutic use
D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; C050883:benidipine hydrochloride; D010643:Phenoxybenzamine; D014700:Verapamil; D004110:Diltiazem; D009543:Nifedipine; D005703:Gallamine Triethiodide