Padam C. Jain

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.

Agents acting on central dopamine receptors.

Dopamine was long believed to be only of functional significance as a precursor of epinephrine and norepinephrine. It became a focus of interest only after Carlsson’s [1] demonstration of its presence in relatively high concentrations in various parts of the brain, mainly striatum [2] and inner retina [3]. Since then there is a growing evidence of the involvement of dopamine as an important neurotransmitter and of the clinical significance of dopaminergic transmission in CNS. It has been suggested that degeneration of the dopaminergic pathway that connects substantia nigra to the caudate nucleus and putamen is a primary feature in the etiology of Parkinson’s disease [4, 5]. Similarly, dopaminergic system has been implicated in the treatment of schizophrenia with antipsychotic drugs [6]. Dopamine agonists and antagonists are thus antiparkinsonian and antipsychotic drugs, respectively, due to their action on central dopamine receptors [7].

Effect of substituents on the stereochemical course of Diels–Alder reaction between β-nitrostyrenes and trans,trans-1,4-diphenylbutadiene

In a study of the Diels–Alder reaction of trans,-trans-1,4-diphenylbutadiene with β-nitrostyrenes a marked stereoselectivity to phenyl “endo” adducts has been observed on introduction of electron-withdrawing substituents in the para-position of the phenyl ring of the β-nitrostyrenes.