A method for in vivo assessment of calcium slow channel blocking drugs

A method is described, using the cardioaccelerator response in pithed rats, that distinguishes calcium entry blockers from other agents which have modes of action not involving direct blockade of calcium entry. Diltiazem (0.01-0.3 mg kg-1), verapamil (0.01-0.03 mg kg-1), nifedipine (0.1-1.0 mg kg-1), propranolol (0.003-0.3 mg kg-1), xylazine (0.01-1.0 mg kg-1), alinidine (0.03-1.0 mg kg-1), and, to a lesser extent, lignocaine (0.1-3.0 mg kg-1), reduced stimulation-evoked sustained cardioaccelerator responses in the pithed rat. BRL 34915 (0.3-10.0 mg kg-1) and nicorandil (1.0-10.0 mg kg-1) were without effect in this situation. Infusion of calcium gluconate (1.0 mg min-1) reversed the reduction of the cardioaccelerator responses by nifedipine (1.0 mg kg-1), verapamil (0.3 mg kg-1), and diltiazem (0.3 mg kg-1) but not to propranolol (0.1 mg kg-1), alinidine (0.5 mg kg-1), or xylazine (0.3 mg kg-1). Therefore, calcium gluconate is selective in reversing the effects of calcium slow channel blockers in this model, thereby making it a useful technique for distinguishing these drugs in vivo.