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Effects of the Enantiomers of (+/-)-HA-966 on Dopamine Neurons: An Electrophysiological Study of a Chiral Molecule

Effects of the Enantiomers of (+/-)-HA-966 on Dopamine Neurons: An Electrophysiological Study of a Chiral Molecule

P D Shepard, S T Connelly, H Lehmann, K C Grobaski

Eur J Pharmacol. 1995 Oct 4;285(1):79-88.

PMID: 8846814

Abstract:

The present study was conducted to evaluate the effects of the resolved enantiomers of (+/-)-1-1 hydroxy-3-aminopyrrolidone-2 ((+/-)-HA-966) on the electrophysiological properties of dopamine-containing neurons in the substantia nigra of the chloral hydrate anesthetized rat. Both (+)- and (-)-HA-966 produced a dose-dependent reduction in firing rate that eventually resulted in total cessation of spontaneous neuronal activity (ID50 = 5.7 and 57.8 mg/kg i.v., respectively). The inhibitory effects of both drugs were accompanied by a marked increase in the regularity of neuronal firing and a concomitant suppression of bursting activity. Although approximately 10-fold less potent than the (-) enantiomer, the inhibitory effects of (+)-HA-966 were completely antagonized by the centrally active, GABAB receptor antagonist, CGP-35348 (300 mg/kg i.v.). These data suggest that the complementary electrophysiological effects of the enantiomers of (+/-)-HA-966 on nigral dopamine neurons are mediated through a common mechanism of action possibly involving a novel interaction with GABAB receptors.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
ALP123690799	CGP 35348 hydrate		123690-79-9 (free acid)	Price

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