Influence of sympathomimetic drugs (1-phenyl-2-amino-ethan-1-ol derivatives) on the biosynthesis of prostaglandins and thromboxane B2.

1--The influence of substituted 1-phenyl-2-amino-ethan-1-ols on prostaglandin and thromboxane biosynthesis was studied using ram seminal vesicle microsomes and homogenates of rat lung and of rat stomach fundus. 2--Clear structure-activity relationships were to be seen regarding the effects of sympathomimetic drugs on prostacyclin (PGI2) biosynthesis in the rat stomach fundus homogenates. 3'- and 4'-Monohydroxy-phenyl derivatives as well as 3',4'-dihydroxy-phenyl derivatives stimulated prostaglandin and thromboxane B2 (TXB2) biosynthesis. Contrary to this the 3',5'-dihydroxy-phenyl derivatives orciprenaline, terbutaline and fenoterol were inhibitors of the biosynthesis in rat organ homogenates. 3--All the sympathomimetic drugs tested stimulated cyclo-oxygenase. Orciprenaline suppressed the adrenaline-activated cyclo-oxygenase in a dose-dependent manner. 4--The effects of adrenoceptor antagonists were also studied. Phenoxybenzamine had little effect on cyclo-oxygenase activity whereas phentolamine markedly increased the rate of oxygen uptake. Both the (+)- and (-)-optical isomers of propranolol had no effect on either basal or adrenaline-stimulated oxygen uptake. In contrast, the (+)- and (-)-isomers of pindolol inhibited basal and adrenaline-stimulated uptake.