Neuroleptic receptors: stereoselectivity for neuroleptic enantiomers.
In order to identify a pair of neuroleptic enantiomers with the highest stereoselective interaction with neuroleptic/dopamine receptors, the effects of eight pairs of neuroleptic enantiomers were tested on the specific binding of 3H-spiperone to crude homogenates of calf caudate nucleus. The ratios of the Ki values were: (+)-butaclamol/(-)-butaclamol = 3000; dexclamol/(-)-analogue = 151; (+)-isobutaclamol/(-)-isobutaclamol = 146; (-)-CTC/(+)-CTC= 109; (-)-centbutindole/(+)-centbutindole = 20; S(+)-octoclothepin/R(-)-octoclothepin = 11. Thus, the neuroleptic receptor is highly stereoselective for the rigid butaclamol derivatives, but much less so for the flexible neuroleptics. The 3H-apomorphine binding site, however, had a stereoselectivity ratio of only 7 for isobutaclamol, further suggesting that the high affinity sites (i.e. nM) for 3H-neuroleptic binding and for 3H-apomorphine binding are different.
D000818:Animals; D014150:Antipsychotic Agents / Q000378:metabolism*; D001058:Apomorphine / Q000378:metabolism; D001665:Binding Sites / Q000187:drug effects; D002069:Butaclamol / Q000378:metabolism; D002417:Cattle; D002421:Caudate Nucleus / Q000378:metabolism; D003533:Cyproheptadine / Q000031:analogs & derivatives / Q000378:metabolism; D003986:Dibenzocycloheptenes / Q000378:metabolism; D003988:Dibenzothiepins / Q000378:metabolism; D007536:Isomerism; D007546:Isoquinolines / Q000378:metabolism; D011955:Receptors, Drug / Q000378:metabolism*; D013134:Spiperone / Q000378:metabolism; D013237:Stereoisomerism
D014150:Antipsychotic Agents; D003986:Dibenzocycloheptenes; D003988:Dibenzothiepins; D007546:Isoquinolines; D011955:Receptors, Drug; D003533:Cyproheptadine; D013134:Spiperone; C020914:isobutaclamol; D002069:Butaclamol; D001058:Apomorphine