Effects of (+)- and (-)-mianserin on alpha-adrenoceptors and tyramine-induced tachycardia in rats.
The individual stereoisomers of mianserin were tested in pithed normotensive rats for their antagonistic activity at vascular postjunctional alpha 1- and alpha 2-adrenoceptors as well as their interaction with the 'amine pump receptor'. (+)-Mianserin was found approximately five times more potent than (-)-mianserin in antagonizing the increase in diastolic pressure brought about by either selective alpha 1 (agonist: methoxamine)- or alpha 2 (agonist: B-HT 920)-adrenoceptor stimulation. (+)-Mianserin also behaved as the more effective displacer of [3H]prazosin and [3H]clonidine binding to rat brain membranes. Tyramine, an indirectly acting sympathomimetic agent, increased the resting heart rate of pithed rats. This effect was competitively antagonised by the noradrenaline uptake inhibitor desipramine. (-)-Mianserin was inactive in inhibiting the tyramine-induced increase in heart rate. (+)-Mianserin showed some activity, but was much less potent than desipramine. The present results clearly indicate that (+)-mianserin is the pharmacologically more active isomer.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003000:Clonidine / Q000378:metabolism; D003891:Desipramine / Q000494:pharmacology; D003984:Dibenzazepines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D008803:Mianserin / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D013237:Stereoisomerism; D014439:Tyramine / Q000494:pharmacology*
D003984:Dibenzazepines; D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D008803:Mianserin; D008729:Methoxamine; D003000:Clonidine; D003891:Desipramine; D014439:Tyramine