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  • Title: Ca2+-antagonistic effects of flurazepam, a benzodiazepine derivative, on isolated guinea-pig left atria.
    Author: Akutagawa K, Makino M, Ishii K.
    Journal: Jpn J Pharmacol; 1983 Aug; 33(4):845-50. PubMed ID: 6632383.
    Abstract:
    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.
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