Evidence that oxmetidine inhibits transmembrane calcium flux in cardiac and vascular tissue

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Abstract
1 Oxmetidine, at concentrations in excess of 1 times 10−6M, caused concentration-dependent negative inotropic and chronotropic responses in guinea-pig isolated heart preparations. 2 Oxmetidine, at concentrations in excess of 1 times 10−5M, caused negative inotropic responses in guinea-pig papillary muscle preparations. The negative inotropic responses to oxmetidine were associated with shortening of the plateau phase of the action potential. 3 Verapamil and nifedipine caused similar shortening of the plateau phase of the action potential at equivalent negative inotropic concentrations indicating that oxmetidine may also act as a calcium antagonist. 4 In preparations partially depolarized by raising extracellular K+ concentration, oxmetidine also exhibited negative inotropic activity and reduced the calcium-dependent action potential. However, unlike verapamil and nifedipine, oxmetidine did not show voltage-dependent activity. 5 Oxmetidine, at concentrations in excess of 1 times 10−5M, inhibited Ca2+-dependent contractions of dog saphenous vein preparations and inhibited 45Ca2+-uptake into veins depolarized by high extracellular K+. 6 In vivo, these calcium antagonist actions of oxmetidine were demonstrated by vasodilatation, reduction in blood pressure, bradycardia and reduced cardiac output in anaesthetized cats. 7 Oxmetidine, at concentrations of 1 times 10−5M and above, shows properties consistent with inhibition of transmembrane Ca2+ flux. This action can be distinguished from other calcium antagonists as the effects of oxmetidine are not voltage-dependent.