On the mechanism of the negative inotropic action of halothane and propanidide.

1. Halothane and propanidide reduce the contractile force of guinea pig isolated atria in a concentration-dependent manner. The approximate concentrations required to bring about a half-maximal pharmacological effect are within the same order of magnitude as the concentrations found in whole blood during general anesthesia of guinea pigs. 2) It seems most likely that the initial effect of halothane or propanidide occurs at the cell membrane. 3) Halothane and propanidide accelerate and enhance the uptake of calcium ions by the cell membrane, so that less ionized calcium will be available for excitation contraction coupling. This phenomenon readily explains the negative inotropic action of both drugs and confirms the presumption that the cell membrane is the initial site of pharmacological attack.