Atypical cardiostimulant beta-adrenoceptor in the XXXX heart: stereoselective antagonism by bupranolol but lack of effect by some bupranolol analogues.

@entity1 @entity10343 @entity1493 @entity35 @entity10341
1. Atypical beta-adrenoceptors resistant to propranolol, but blocked by bupranolol, increase contractile force and/or frequency of the heart in @entity1 and @entity35 . We compared the potencies of the enantiomers of bupranolol and examined the possible effects of seven bupranolol analogues including bevantolol ( @entity1493 ) at this receptor in pithed and vagotomized @entity35 . 2. CGP 12177, an agonist of the atypical beta-adrenoceptor, increased heart rate dose-dependently. Its dose-response curve was shifted to the right by S-(-)-bupranolol 10 micro mol kg(-1) by a factor of 8.4, but not affected by the same dose of R-(+)-bupranolol. 3. Desmethylbupranolol and compounds BK-21, BK-22, BK-23 and BK-25 also increased heart rate dose-dependently. The @entity10343 antagonist CGP 20712 given in combination with the @entity10341 antagonist ICI 118,551 (0.1 micro mol kg(-1) each) reduced the positive chronotropic action of the five bupranolol analogues without affecting that of CGP 12177. The potencies of the bupranolol analogues to increase heart rate were correlated (r=0.91, P<0.05) with their affinities for @entity10343 binding sites in @entity35 brain cortex membranes labelled with [(3)H]CGP 12177 (in the presence of ICI 118,551). 4. BK-26 and @entity1493 , 10 micro mol kg(-1) each, had only minor effects on heart rate by themselves and did not antagonize the effect of CGP 12177. However, at 1 micro mol kg(-1), they antagonized the increase in heart rate elicited by the @entity10343 agonist prenalterol. 5. In conclusion, bupranolol is a stereoselective antagonist at the atypical cardiostimulant beta-adrenoceptor. The effects of the bupranolol analogues are related to the activation or blockade of beta(1)-adrenoceptors, but not of atypical beta-adrenoceptors.
