SD-3211, a novel benzothiazine calcium antagonist, alone and in combination with a beta-adrenoceptor antagonist, produces antihypertensive effects without affecting heart rate and atrioventricular conduction in conscious renal hypertensive dogs.

Abstract

We compared the effects of SD-3211, a novel calcium antagonist, on blood pressure, heart rate, and atrioventricular conduction with those of diltiazem using conscious renal hypertensive dogs (one-kidney, one-clip type). We also examined the combined effects of these calcium antagonists with a beta-adrenoceptor antagonist, propranolol, on these variables. Oral administration of SD-3211 (1.25, 2.5, and 5 mg/kg) resulted in a dose-dependent decrease in blood pressure without affecting heart rate. SD-3211 at all three doses significantly decreased systolic blood pressure. At 2.5 and 5 mg/kg the compound elicited significant decreases in mean blood pressure and diastolic blood pressure. Hypotension obtained with the highest dose of SD-3211 lasted for at least 9 h. No significant alteration in PR interval was observed in electrocardiograms after administration of SD-3211. Diltiazem, given orally at doses of 2.5 and 5 mg/kg but not 1.25 mg/kg, produced significant hypotension with little change in heart rate. The duration of hypotension induced by the highest dose of diltiazem was only 3 h. Diltiazem prolonged PR interval in a dose-dependent manner, causing second-degree atrioventricular block in some dogs. Combined administration of SD-3211 or diltiazem (2.5 mg/kg) with propranolol (30 mg/kg) resulted in enhanced hypotension with no alteration in heart rate. SD-3211 plus propranolol had little effect on the PR interval, whereas diltiazem plus propranolol caused a markedly enhanced prolongation. These results indicate that SD-3211 is an antihypertensive agent with long-lasting action and little effect on heart rate and atrioventricular conduction and, when administered alone or in combination with propranolol, may be useful in the treatment of hypertension.

• Authors: M Kageyama, K Nishimura, T Takada, N Miyawaki, H Yamauchi
• Journal: Journal of cardiovascular pharmacology (J Cardiovasc Pharmacol) Vol. 17 Issue 1 Pg. 102-7 (Jan 1991) ISSN: 0160-2446 [Print] United States
• PMID: 1708042 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Adrenergic beta-Antagonists
• Antihypertensive Agents
• Calcium Channel Blockers
• Thiazoles
• Propranolol
• sesamodil
• Diltiazem

Topics

• Administration, Oral
• Adrenergic beta-Antagonists (pharmacology)
• Animals
• Antihypertensive Agents (administration & dosage, pharmacology)
• Atrioventricular Node (drug effects, physiology)
• Blood Pressure (drug effects)
• Calcium Channel Blockers (administration & dosage, pharmacology)
• Diltiazem (administration & dosage, pharmacology)
• Dogs
• Drug Therapy, Combination
• Electrocardiography (drug effects)
• Heart Rate (drug effects)
• Hypertension, Renal (drug therapy, physiopathology)
• Male
• Propranolol (pharmacology)
• Thiazoles (administration & dosage, pharmacology)