Colonic and Cardiovascular Actions of the Atypical β‐Adrenergic Agonist SR 58611A in Rats

Inhibition of colonic myoelectric activity by the new atypical β‐adrenergic agonist SR 58611A and its cardiovascular effects were investigated in orally dosed unanesthetized rats. SR 58611A and the reference compound ritodrine caused dose‐related reduction of the long spike burst frequency of the proximal colon (respective ED50values of 0.47 and 3.1 mg/kg); this was prevented by alprenolol but not by the β1‐ or β2‐selective adrenergic antagonists CGP 20712A and ICI 118,551. The minimal effective doses of SR 58611A and ritodrine raising heart rate were about 20 and 3 times their respective ED50values for inhibition of colonie motility. Ritodrine, unlike SR 58611A, caused a dose‐dependent increase in heart rate. Blood pressure was not affected by either drug. There was partial tolerance to the intestinal effects of SR 58611A and ritodrine, which fell by about half after 4 days' treatment but no further after 8 days. In the animal model investigated, SR 58611A was less liable than ritodrine to induce cardiovascular side effects. It should thus be of prospective therapeutic interest for intestinal hypermotility disorders.