Serotonergic properties of spiroxatrine enantiomers.
The neuroleptic drug spiperone (1) has proven very useful in the characterization of putative serotonin (5-hydroxytryptamine, 5-HT) receptors. Thus, 5-HT1 receptors have been divided into subtypes based on their affinities for 1: 5-HT1A sites have high affinity, while 5-HT1B sites have low affinity. However, the usefulness of 1 for the pharmacological characterization of 5-HT1A sites is limited because of its high affinity for 5-HT2 (as well as D2-dopaminergic) receptors. A close analogue of 1, (+/-)-spiroxatrine (2), has much higher affinity for 5-HT1A receptors and much lower affinity for 5-HT2 receptors. We report here the stereospecific synthesis of (R)-(+)- and (S)-(-)-spiroxatrine enantiomers and their evaluation at several 5-HT receptors and D2-dopaminergic and alpha 1-adrenergic receptors.
D000818:Animals; D014150:Antipsychotic Agents / Q000378:metabolism; D001665:Binding Sites; D004146:Dioxanes / Q000378:metabolism*; D004147:Dioxins / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000378:metabolism*; D012701:Serotonin / Q000494:pharmacology*; D013134:Spiperone / Q000378:metabolism; D013141:Spiro Compounds / Q000378:metabolism*; D013237:Stereoisomerism
D014150:Antipsychotic Agents; D004146:Dioxanes; D004147:Dioxins; D011985:Receptors, Serotonin; D013141:Spiro Compounds; D012701:Serotonin; D013134:Spiperone; C018387:spiroxatrine