Antagonistic effects of some metabolites and analogues of mianserin on serotonin and alpha 1- and alpha 2-adrenergic receptors in the flexor reflex model in vivo.

Mianserin, its two metabolites desmethylmianserin (Org OH-46) and 8-hydroxymianserin (Org GF-45), and its two analogues R(-)-6-aza-mianserin (Org 44-19) and S(+)-6-aza-mianserin (Org 44-20) were tested for their antagonistic action on the central serotonin (5-HT) receptor and alpha-adrenoceptors in the flexor reflex model in vivo in the spinal rat. The ability to reduce the increase in the flexor reflex activity induced by quipazine (a 5-HT receptor agonist), St 587 (an alpha 1-adrenoceptor agonist), or clonidine (an alpha 2-adrenoceptor agonist) was a measure of their potencies as antagonists of the respective receptors. All the compounds occurred to be potent antagonists of the central 5-HT receptor (S(+)-6-aza-mianserin was most active) and, to a lesser degree, of alpha-adrenoceptors with preferential antagonistic action on alpha 2-subtype.