Neuroleptic receptors: stereoselectivity for neuroleptic enantiomers

Abstract

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 K_i 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.