Beneficial effect of the novel thromboxane A2 receptor antagonist sodium (E)-11-[2-(5,6-dimethyl-1-benzimidazolyl)ethylidene]-6,11- dihydrodibenz[b,e]oxepine-2-carboxylate monohydrate on collagen-induced coronary ischemia in guinea-pigs.

Abstract

The effect of KW-3635 (sodium (E)-11-[2-(5,6-dimethyl-1-benzimidazolyl) ethylidene]-6,11-dihydrodibenz[b,e] oxepine-2-carboxylate monohydrate, CAS 127166-41-0), a novel thromboxane A2 (TxA2) receptor antagonist, on collagen-induced coronary ischemia was studied in guinea-pigs. Under pentobarbital anaesthesia, intravenous injection (i.v.) of collagen (1 mg/kg) induced abnormal ECG changes such as ST-T changes, elevation of T-wave arrhythmia and cardiac arrest in severe cases. The changes of ECG (leads I, II and III) were recorded for 10 min following collagen injection. KW-3635 (25-50 mg/kg p.o.) remarkably improved the collagen-induced ischemic ECG changes. The effect of KW-3635 was more potent than those of daltroban, isbogrel and ticlopidine. Neither nifedipine nor propranolol had any effect. The plasma thromboxane B2 level in the KW-3635-treated animals was lower in comparison with those in both the control and daltroban-treated animals. These results suggest that TxA2 may play a role in this model of coronary ischemia and that KW-3635 is effective in the treatment of ischemic heart disease.

• Authors: M Kawakage, S Shirakura, A Karasawa, M Takeda, I Miki, A Ishii, K Kubo
• Journal: Arzneimittel-Forschung (Arzneimittelforschung) Vol. 41 Issue 12 Pg. 1246-50 (Dec 1991) ISSN: 0004-4172 [Print] Germany
• PMID: 1815524 (Publication Type: Journal Article)

Chemical References

• Benzimidazoles
• Benzoxepins
• Cyclooxygenase Inhibitors
• Phenylacetates
• Sulfonamides
• Thromboxanes
• Thromboxane B2
• Thromboxane A2
• Collagen
• Propranolol
• Nifedipine
• Ticlopidine
• daltroban
• KW 3635

Topics

• Animals
• Arrhythmias, Cardiac (physiopathology)
• Benzimidazoles (therapeutic use)
• Benzoxepins (therapeutic use)
• Collagen
• Coronary Disease (chemically induced, drug therapy, physiopathology)
• Cyclooxygenase Inhibitors (pharmacology)
• Electrocardiography (drug effects)
• Guinea Pigs
• Heart Arrest (chemically induced, physiopathology)
• Male
• Nifedipine (therapeutic use)
• Phenylacetates (pharmacology)
• Propranolol (therapeutic use)
• Sulfonamides (pharmacology)
• Thromboxane A2 (antagonists & inhibitors)
• Thromboxane B2 (blood)
• Thromboxanes (antagonists & inhibitors)
• Ticlopidine (therapeutic use)