Activities of octopamine and synephrine stereoisomers on α‐adrenoceptors

Abstract

1 The activities of the (-)-and (+ )-forms of m-and p-octopamine and m-and p-synephrine on a,-adrenoceptors from rat aorta and anococcygeus and a2-adrenoceptors from rabbit saphenous vein were compared with those of noradrenaline (NA).2 The rank order of potency of the (-)-forms on cx,-adrenoceptors from rat aorta and a2-adrenoceptors was NA > m-octopamine = m-synephrine > p-octopamine = p-synephrine. The two m-compounds were 6 fold less active than NA on x,-adrenoceptors from rat aorta and 150 fold less active on x,-adrenoceptors. The two p-compounds were 1,000 fold less active than NA on both oqadrenoceptors from rat aorta and x2-adrenoceptors. The rank order ofpotency ofthe (-)-forms on oqadrenoceptors 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 pcompounds 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 a,-and M2-adrenoceptors. The potency ofeach ( + )-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 a,-and M2-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 a-adrenoceptor subtypes, it is concluded that the rat aorta contains only a,-adrenoceptors while the rabbit saphenous vein possesses predominantly M2-adrenoceptors.5 Ligand binding data for the octopamine and synephrine stereoisomers at oq-and a2-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 a,-and M2-binding sites was NA > m-octopamine = msynephrine >p-synephrine >p-octopamine. The relative affinities ofthe members ofthe series against a,-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 x2-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 a,-adrenoceptors from rat aorta or x2-adrenoceptors; however, m-synephrine is more active than m-octopamine on a,-adrenoceptors from rat anococcygeus. Both m-octopamine and msynephrine can be considered to be naturally occurring x,-selective amines. However, if m-and poctopamine are co-released with NA in amounts proportional to their concentration, it is concluded that their activities on m,-and x2-adrenoceptors are too low to be ...

α1A‐Adrenoceptors mediate contractions to phenylephrine in rabbit penile arteries

“…Similar to the cavernous artery, the potency order of antagonists pointed to a 1A -AR, but the low Schild slopes did not confirm competitive antagonism. Both NA, and to a lesser extent, PE (Brown et al, 1988), at high concentrations can act at a 2 -ARs. Rabbit penile tissue, specifically corpus cavernosum strips (Gupta et al, 1998), has been demonstrated to possess functional post-junctional a 2 -ARs in addition to the predominant a 1 -ARs.…”

The Action of <i>p</i>-Synephrine on Lipid Metabolism in the Perfused Rat Liver

“…[1-14 C]oleic acid (56 mCi/mmol) and [1][2][3][4][5][6][7][8][9][10][11][12][13][14] C]octanoic acid (50 mCi/mmol).…”

“…It has been shown, for example, that p-synephrine binds to serotoninergic receptors [4]. Likewise, an action of p-synephrine via adrenergic receptors has been documented [5] [6] [7]. Acute oral administration of elevated doses of a C. aurantium extract or psynephrine produced reversible toxic effects, probably due to unspecific adrenergic stimulation [3].…”

ESCO report: Advice on the EFSA guidance document for the safety assessment of botanicals and botanical preparations intended for use as food supplements, based on real case studies

“…The adrenergic activities of (+)-isomers are at least 1 to 2-fold lower than those of their (-)-counterparts. The activities of the respective synephrine and octopamine isomers towards α-adrenoceptors are about 1 or 2 orders of magnitude higher compared to their activities towards β-adrenoceptors (Jordan et al 1987, Brown et al 1988, Evans et al 1988, Pellati et al 2002, Pellati & Benvenuti 2007, Avula et al 2005.…”

“…aurantium L.). Moreover, potential additive effects of the p-synephrine, m-synephrine and/or octopamine are to be considered in such cases (Jordan et al 1987, Brown et al 1988, Evans et al 1988, NTP/NIEHS 2004, Blumenthal 2005). …”