Alpha 1-adrenoceptor-mediated vasoconstriction in vivo to enantiomers of SK & F 89748-A.

The pressor activity of the 1-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 1-phenylephrine. The d-enantiomer was half as potent. The log dose-pressor effect curves for d- and 1-SK & F 89748-A were not influenced by reserpine treatment (2 X 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 1-enantiomer in pithed cats. It is concluded that d- and 1-SK & F 89748-A are potent, directly acting highly selective agonists of (vascular) postjunctional alpha 1-adrenoceptors. Potency and selectivity were equally pronounced for both enantiomers. The currently available selective agonists of alpha 1-adrenoceptors, including the optical isomers of SK & F 89748-A, cannot distinguish between alpha 1- and alpha 2-adrenoceptors. This conclusion is based on binding affinity since these affinities are linearly correlated as shown by radioligand displacement experiments.