Effects of semotiadil (SD-3211), a benzothiazine calcium antagonist, on blood pressure and atrioventricular conductivity in anesthetized dogs.
We investigated the effects of semotiadil (SD-3211), a novel calcium antagonist, on blood pressure and the atrioventricular (AV) conduction time and functional refractory period (FRP) of the AV conduction system (AV conductivity) in anesthetized open-chest dogs. The heart was electrically stimulated at a constant rate. In dogs with an intact nerve supply to the heart, i.v.-injections of semotiadil (0.03 to 0.3 mg/kg) produced a fall of blood pressure in a dose-dependent manner. AV conduction time and FRP were prolonged by rather higher doses (0.3 mg/kg), and second-degree AV block occurred only with the highest dose (1 mg/kg). In dogs with the nerve supply to the heart interrupted, the vasodepressor effects and suppressant effects of semotiadil on AV conductivity were slightly enhanced. The suppressant effects on AV conductivity became marked as pacing rates were increased. These results suggest that semotiadil at appropriate doses produces a vasodepressor effect without affecting AV conductivity even in the heart deprived of nervous control, e.g., the heart with beta-adrenoceptors blocked. The frequency-dependent suppressant effect on FRP of semotiadil is also noteworthy in the treatment of reentrant supraventricular tachycardia that involves the AV node.
Kageyama
M
M
Department of Pharmacology, Tohoku University School of Medicine, Sendai, Japan.
Yamada
H
H
Satoh
K
K
Taira
N
N
D000758:Anesthesia; D000818:Animals; D001283:Atrioventricular Node / Q000187:drug effects* / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004285:Dogs; D005260:Female; D008297:Male; D009431:Neural Conduction / Q000187:drug effects; D013233:Stellate Ganglion / Q000502:physiology; D013844:Thiazoles / Q000494:pharmacology*; D014628:Vagotomy; D014630:Vagus Nerve / Q000502:physiology
D002121:Calcium Channel Blockers; D013844:Thiazoles; C064356:sesamodil