Ca2+-antagonistic effects of flurazepam, a benzodiazepine derivative, on isolated guinea-pig left atria.
Effects of flurazepam, a benzodiazepine derivative, on Ca2+-induced cardio-stimulant contractile activity in normal Tyrode's solution and Ca2+-mediated contraction in K+-rich (19-22 mM) Tyrode's solution were investigated in electrically driven left atrial preparations isolated from guinea-pigs. In normal Tyrode's solution, flurazepam (1 X 10(-6), 1 X 10(-5) and 1 X 10(-4) M) noncompetitively shifted the dose-response curves for CaCl2 downwards. In K+ (19 mM)-rich Tyrode's solution, flurazepam (3 X 10(-5) M) decreased contractile amplitude time-dependently; and after addition of CaCl2 (final: 8 mM), contractile amplitude was increased time-dependently. In K+ (19 mM)-depolarized preparations, flurazepam (3 X 10(-5) M) competitively shifted the dose-response curve for CaCl2 rightwards. In the K+ (22 mM)-depolarized isoproterenol (3.8 X 10(-6) M)-treated atrial preparation, flurazepam (3 X 10(-5) M) consistently suppressed contraction. Flurazepam (9 X 10(-5) M) suppressed atrial contraction in tetrodotoxin (TTX) (2 X 10(-5) M)-added normal Tyrode's solution, and CaCl2 (final: 8 mM) partially restored the contraction. These results suggest that flurazepam inhibits transmembrane Ca2+-influx into the atrial muscle cell.
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002121:Calcium Channel Blockers; D002122:Calcium Chloride / Q000494:pharmacology; D004558:Electric Stimulation; D005260:Female; D005479:Flurazepam / Q000494:pharmacology*; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D013779:Tetrodotoxin / Q000494:pharmacology
D002121:Calcium Channel Blockers; D013779:Tetrodotoxin; D005479:Flurazepam; D007545:Isoproterenol; D002122:Calcium Chloride; D002118:Calcium