Cardiac muscarinic blocking and atropinic blocking effects of a tetramine disulfide and alpha-adrenoceptor blocking activity.

Abstract

Since many alpha-adrenoceptor blocking drugs were known to have muscarinic blocking activity, BHC, a newly synthesized tetramine disulfide with alpha-adrenoceptor blocking activity, and two of its analogs were tested for muscarinic blocking activity in the isolated guinea pig atrium and ileum. BHC had muscarinic blocking activity. Its potency was higher in the atrium than in the ileum. The cardiac muscarinic blocking potency of the analog that contained carbon atoms instead of sulfur atoms was similar to that of BHC. Lower concentrations of the drugs antagonized inotropic effects of acetylcholine competitively, but higher concentrations had a smaller effect than expected for competitive antagonism. In the atrium BHC competitively inhibited the muscarinic blocking effect of atropine. Its atropinic blocking potency was similar to the muscarinic blocking potency. Quinidine and gallamine also had muscarinic blocking and atropinic blocking effects in the atrium but were about 10 times less potent than BHC.