Pharmacological profile of a novel 1,5-benzothiazepine calcium antagonist.
The in vitro cardiovascular effects of a new 1,5-benzothiazepine derivative, RS-5773 ((2S,3S)-3-acetoxy-8-benzyl-2,3-dihydro-5-[2-(dimethylamino)ethyl]-2-(4- methoxy-phenyl)-1,5-benzothiazepine-4-(5H)-one hydrochloride, CAS 129173-57-5), were examined in isolated rat aorta and isolated guinea pig heart preparations. Like diltiazem or nifedipine, RS-5773 preferentially relaxed K(+)-contracted aorta rather than phenylephrine-contracted aorta, suggesting that the agent interfered with calcium channels. Vasorelaxant effects of RS-5773 on K(+)-contracted aorta was about 5 times more potent than those of diltiazem. The vasorelaxation with RS-5773 developed very slowly and was resistant to washout. The negative effects of the agent on contractile force of guinea pig papillary muscles and beating rate of guinea pig atria were not much different from those of diltiazem, although the actions of RS-5773 developed more slowly than those of diltiazem. These results indicate that RS-5773 is a diltiazem congener with vascular preference and long-lasting actions. In this respect, RS-5773 resembled clentiazem. But vascular and cardiac effects of RS-5773 developed more slowly than those of clentiazem and they were more resistant to washout.
Shiga
H
H
Research Laboratories, Sankyo Co. Ltd., Tokyo, Japan.
Miyake
S
S
Ideka
M
M
Ito
Y
Y
Yanagisawa
H
H
Koike
H
H
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004110:Diltiazem / Q000031:analogs & derivatives / Q000494:pharmacology; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D010210:Papillary Muscles / Q000187:drug effects; D010656:Phenylephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013841:Thiazepines / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D013841:Thiazepines; C076757:RS 5773; D010656:Phenylephrine; C056595:clentiazem; D011189:Potassium Chloride; D004110:Diltiazem