THE M-RECEPTOR ANTAGONISM OF A NEW CHOLINOLYTIC COMPOUND TBBB IN COMPARISON WITH HYOCINE BROMIDE (HBB) AND ATROPINE

The radioreceptor assay using ³H-QNB as a ligand on cardiac membrane preparation and determination of pA₂ and pA₁₀ on isolated atria and ileum of guinea-pig were performed for comparing the potency of M-receptor antagonism of a new cholinolytic compound TBBB with that of HBB and atropine. Taking the potency of atropine as 1, the inhibition action of TBBB and HBB on ³H-QNB bindings to cardiac membrane preparation corresponded to 1/77 and 1/59, respectively. The antagonistic action of both in this respect was almost the same. The antagonism of inhibition induced by Ach on contractility of guinea-pig atria, however, was 1/8.9 and 1/26.5 for TBBB and HBB, respectively. The cholinolytic effect of TBBB and HBB on isolated guinea-pig ileum was 1/11.2 and 1/21,9, respectively, showing that the former is more potent to relax the spasm of gastro-intestinal smooth muscle. The mode of antagonism was believed to be competitive based on the fact that the difference of PA₂ and PA₁₀ observed was about 0.95 which was the same for all the three compounds. TBBB, which is less expensive and easier to produce, is warranted for clinical applications.