Activities of octopamine and synephrine stereoisomers on α‐adrenoceptors

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Abstract
1 The activities of the (-)- and (+)-forms of m- and p-octopamine and m- and p-synephrine on α1-adrenoceptors from rat aorta and anococcygeus and α2-adrenoceptors from rabbit saphenous vein were compared with those of noradrenaline (NA). 2 The rank order of potency of the (-)- forms on α1-adrenoceptors from rat aorta and α2-adrenoceptors was NA > m-octopamine = m-synephrine > p-octopamine = p-synephrine. The two m-compounds were 6 fold less active than NA on α1-adrenoceptors from rat aorta and 150 fold less active on α2-adrenoceptors. The two p-compounds were 1,000 fold less active than NA on both α1-adrenoceptors from rat aorta and α2-adrenoceptors. The rank order of potency of the (-)- forms on α1-adrenoceptors from rat anococcygeus was NA = m-synephrine > m-octopamine > p-octopamine = p-synephrine. m-Octopamine was 4 fold less active than NA and (-)-m-synephrine. The two p-compounds were 30 fold less active than NA. 3 The rank order of potency of the (+)- forms was NA > m-octopamine > m-synephrine > p-octopamine > p-synephrine on both α1- and α2-adrenoceptors. The potency of each (+)- form was 1–2 orders of magnitude less than that of the (-) counterpart, the differences being greater for the stereoisomers of synephrine than for those of octopamine on both α1- and α2-adrenoceptors. 4 The yohimbine diastereoisomer antagonists, rauwolscine and corynanthine, were tested against (-)-NA and (-)-m-octopamine-induced contractions in both preparations. Based upon the known selectivities of these isomers for α-adrenoceptor subtypes, it is concluded that the rat aorta contains only α1-adrenoceptors while the rabbit saphenous vein possesses predominantly α2-adrenoceptors. 5 Ligand binding data for the octopamine and synephrine stereoisomers at α1- and α2-binding sites from rat cerebral cortex was also obtained. (-)-Forms were more active than (+)-forms. The rank order of affinity of the (-)-forms for both α1- and α2-binding sites was NA > m-octopamine = m-synephrine > p-synephrine > p-octopamine. The relative affinities of the members of the series against α1-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 (-)-NA were much greater at the α2-binding sites than were the relative activities in rabbit saphenous vein, possibly suggesting low intrinsic efficacy. Functional antagonist responses to NA by the (-)-octopamine and synephrines could not, however, be demonstrated on rat aorta or rabbit saphenous vein. 6 The activities of m-octopamine and m-synephrine were not significantly different from each other on either α1-adrenoceptors from rat aorta or α2-adrenoceptors; however, m-synephrine is more active than m-octopamine on α1-adrenoceptors from rat anococcygeus. Both m-octopamine and m-synephrine can be considered to be naturally occurring α1-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 α1- and α2-adrenoceptors are too low to be physiologically significant.