Opposing anticholinergic and cardio-depressive effects of promazine and thioridazine in isolated rat atria.

: Acetylcholine (ACh) reduced both the rate of contraction and the contractile force in isolated rat atria, but these effects were less pronounced after the preparations had been treated with promazine or thioridazine. The anticholinergic activity of the phenothiazines was counteracted by their direct cardiodepressive effects. In electrically stimulated atria treated with promazine 5 × 10-6M, the anticholinergic effect was dominant, the reduction in contractile force was less than that produced by ACh when acting alone. In the spontaneously beating atria promazine 5 × 10-6M produced a depression of frequency which balanced the anticholinergic effect. The reduction in the work index produced by ACh was less in the presence of promazine 5 × 10-6M because of the anticholinergic effect on the contractile force. The cardiodepressive effects of thioridazine 5 × 10-6M and promazine 10-5M and 2.5 × 10-5M balanced or exceeded the anticholinergic effects; the reductions in cardiac performance were equal to, or greater than those produced by ACh when acting alone. It is suggested that the anticholinergic activity of phenothiazine derivatives is unspecific i.e. not due to receptor blockade, but to general membrane stabilizing effects, which counteract the changes in membrane permeability produced by ACh.