The blockade of alpha 2-adrenoceptors by the PNMT inhibitaor SK&F 64139.

Three tetrahydroisoquinolines were tested for activity on central alpha 2-adrenoceptors by determining their ability to inhibit [3H]clonidine binding to rat cerebral cortical membrane homogenates. The compounds included the PNMT inhibitors SK&F 64139 (7,8-dichloro-1,2,3,4-tetrahydroisoquinoline) and SK&F 29661 (1,2,3,4-tetrahydroisoquinoline 7-sulfonamide) as well as SK&F 72223 (5,8-dimethoxy-1,2,3,4-tetrahydroisoquinoline) a structural analogue inactive as a PNMT inhibitor. SK&F 64139 and SK&F 72223 but not SK&F 29661 inhibited [3H]clonidine binding. Studies in the isolated guinea pig atrium confirmed that SK&F 64139 and SK&F 72223 are alpha 2-adrenoceptor antagonists.