α1-adrenoceptor-mediated vasoconstriction in vivo to enantiomers of SK&F 89748-A

Abstract The pressor activity of the l-enantiomer of SK&F 89748-A, 1,2,3,4-tetrahydro-8-methoxy-5-(methylthio)-2-naphthalenamine, in pithed normotensive rats was found comparable with that of l-phenylephrine. The d-enantiomer was half as potent. The log dose-pressor effect curves for d- and l-SK&F 89748-A were not influenced by reserpine treatment (2×5 mg/kg i.p., −48 and −24 h), were virtually unaffected by yohimbine (1 mg/kg i.v., −15 min) but were markedly shifted to the right by prazosin (0.1 mg/kg i.v., −15 min) and phentolamine (1 mg/kg i.v., −15 min). Similar observations were made for the l-enantiomer in pithed cats. It is concluded that d- and l-SK&F 89748-A are potent, directly acting highly selective agonists of (vascular) postjunctional α 1 -adrenoceptors. Potency and selectivity were equally pronouncd for both enantiomers. The currently available selecte agonists of α 1 -adrenoceptors, including the optical isomers of SK&F 89748-A, cannot distinguish between α 1 - and α 2 -adrenoceptors. This conclusion is based on binding affinity since these affinities are linearly correlated as shown by radioligand displacement experiments.