Activities of octopamine and synephrine stereoisomers on α‐adrenoceptors
Authors: Brown C.M. , McGrath J.C. , Midgley J.M. , Muir A.G.B. , O'Brien J.W. , Thonoor C.M. , Williams C.M. , Wilson V.G. 
Published: July 2012

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).

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.

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.

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.

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.

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.