Stereoselective interaction of mianserin with 5-HT3 receptors.
The interaction of the enantiomers of mianserin with the 5-HT3 receptor was determined. Using [3H]granisetron binding, (-)-mianserin was more potent than (+)-mianserin (pKi 8.46 and 6.95, respectively). The enantiomers competitively antagonized the depolarizing effect of 5-hydroxytryptamine in the rat vagus nerve preparation (pKapp: (-)-mianserin 8.13, (+)-mianserin 6.58). This stereoselectivity was maintained in-vivo as determined using ex-vivo inhibition of [3H]granisetron binding. Therefore, in contrast to its enantiomeric selectivity for the 5-HT1C and 5-HT2 receptors, where the (+)-isomer is more potent, the enantiomeric 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.
Wood
M D
MD
SmithKline Beecham, Harlow, Essex, UK.
Thomas
D R
DR
Watkins
C J
CJ
Newberry
N R
NR
D000818:Animals; D004347:Drug Interactions; D017829:Granisetron / Q000378:metabolism / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008803:Mianserin / Q000378:metabolism / Q000494:pharmacology*; D008954:Models, Biological; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism; D013237:Stereoisomerism; D014316:Tritium; D014630:Vagus Nerve / Q000187:drug effects / Q000648:ultrastructure
D017829:Granisetron; D008803:Mianserin; D011985:Receptors, Serotonin; D014316:Tritium