ACTIVITIES OF OCTOPAMINE AND SYNEPHRINE STEREOISOMERS ON ALPHA-ADRENOCEPTORS

The activities of the (.sbd.)- and (+)-forms of m- and p-octopamine and m- and p-synephrine on .alpha.1-adrenoceptors from rat aorta and anococcygeus and .alpha.2-adrenoceptors from rabbit saphenous vein were compared with those of noradrenaline (NA). The rank order of potency of the (.sbd.)- forms on .alpha.1-adrenoceptors from rat aorta and .alpha.2- adrenoceptors was NA > m-octopamine = m-synephrine > p-octopamine = p-synephrine. The two m-compounds were 6 fold less active than NA on .alpha.1-adrenoceptors from rat aorta and 150 fold less active on .alpha.2-adrenoceptors. The two p-compounds were 1,000 fold less active than NA on both .alpha.1-adrenoceptors from rat aorta and .alpha.2-adrenoceptors. The rank order of potency of the (.sbd.)- forms on .alpha.1-adrenoceptors from rat anococcygeus was NA = m-synephrine > m-octopamine > p-octopamine = p-synephrine. m-Octopamine was 4 fold less active than NA and (.sbd.)-m-synephrine. The two p-compounds were 30 fold less active than NA. The rank order of potency of the (+)- forms was NA > m-octopamine > m-synephrine > p-octopamine > p-synephrine on both .alpha.1- and .alpha.2-adrenoceptors. The potency of each (+)- form was 1-2 orders of magnitude less than that of the (.sbd.) counterpart, the differences being greater for the stereoisomers of synephrine than for those of octopamine on both .alpha.1- and .alpha.2-adrenoceptors. The yohimbine diastereoisomer antagonists, rauwolscine and corynanthine, were tested against (.sbd.)-NA and (.sbd.)-m-octopamine-induced contractions in both preparations. Based upon the known selectivities of these isomers for .alpha.-adrenoceptor subtypes, it is concluded that the rat aorta contains only .alpha.1-adrenoceptors while the rabbit saphenous vein possesses predominantly .alpha.2-adrenoceptors. Ligand binding data for the octopamine and synephrine stereoisomers at .alpha.1- and .alpha.2-binding sites from rat cerebral cortex was also obtained. (.sbd.)-Forms were more active than (+)-forms. The rank order of affinity of the (.sbd.)-forms for both .alpha.1- and .alpha.2-binding sites was NA > m-octopamine = m-synephrine > p-synephrine > p-octopamine. The relative affinities of the members of the series against .alpha.1-binding sites were very similar to their relative functional activities on rat aorta. However, the affinities of both m- and p-compounds relative to that of (.sbd.)-NA were much greater at the .alpha.2-binding sites than were the relative activities than were the relative activities in rabbit saphenous vein, possibly suggesting low intrinsic efficacy. Functional antagonist responses to NA by the (.sbd.)-octopamine and synephrines could not, however, be demonstrated on rat aorta or rabbit saphenous vein. The activities of m-octopamine and m-synephrine were not significantly different from each other on either .alpha.1-adrenoceptors from rat aorta or .alpha.2-adrenoceptors; however, m-synephrine is more active than m-octopamine on .alpha.1-adrenoceptors from rat anococcygeus. Both m-octopamine and m-synephrine can be considered to be naturally occurring .alpha.1-selective amines. However, if m- and p-octopamine are co-released with NA in amounts proportional to their concentration, it is concluded that their activities on .alpha.1- and .alpha.2-adrenoceptors are too low to be physiologically significant.