STEREOSELECTIVE INTERACTION OF MIANSERIN WITH 5-HT3 RECEPTORS

The interaction of the enantiomers of mianserin with the 5-HT3 recepto r was determined. Using [H-3]granisetron binding, (-)-mianserin was mo re potent than (+)-mianserin (pK(i) 8.46 and 6.95, respectively). The enantiomers competitively antagonized the depolarizing effect of 5-hyd roxytryptamine in the rat vagus nerve preparation (pK(app): (-)-mianse rin 8.13, (+)-mianserin 6.58). This stereoselectivity was maintained i n-vivo as determined using ex-vivo inhibition of [H-3]granisetron bind ing. Therefore, in contrast to its enantiomeric selectivity for the 5- HT1C and 5-HT2 receptors, where the (+)-isomer is more potent, the ena ntiomeric selectivity of mianserin for the 5-HT3 receptor was reversed . This differential selectivity of the enantiomers of mianserin may be useful in elucidating its utility in anxiety states.