Ca2+-antagonistic effects of flurazepam, a benzodiazepine derivative, on isolated guinea-pig left atria.

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Abstract
Effects of flurazepam, a benzodiazepine derivative, on Ca2+-induced cardiostimulant 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 .times. 10-6, 1 .times. 10-5 and 1 .times. 10-4 M) noncompetitively shifted the dose-response curves for CaCl2 downwards. In K+(19 mM)-rich Tyrode''s solution, flurazepam (3 .times. 10-5 M) decreased contractile amplitude time dependently; after addition of CaCl2 (final: 8 mM), contractile amplitude was increased time dependently. In K+(19 mM)-depolarized preparations, flurazepam (3 .times. 10-5 M) competitively shifted the dose-response curve for CaCl2 rightwards. In the K+(22 mM)-depolarized isoproterenol (3.8 .times. 10-6 M)-treated atrial preparation, flurazepam (3 .times. 10-5 M) consistently suppressed contraction. Flurazepam (9 .times. 10-5 M) suppressed atrial contraction in tetrodotoxin (TTX) (2 .times. 10-5 M)-added normal Tyrode''s solution, and CaCl2 (final: 8 mM) partially restored the contraction. Flurazepam apparently inhibits transmembrane Ca2+-influx into the atrial muscle cell.