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Heterocyclic GABA analogues. Displacement of radiolabelled 3H-GABA from rat brain membrane preparations - PubMed

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  • PMID: 2820789

Heterocyclic GABA analogues. Displacement of radiolabelled 3H-GABA from rat brain membrane preparations

M Varasi et al. Farmaco Sci. 1987 Jun.

Abstract

2,5-Dimethyl-1H-pyrrol-1-yl-butanoic acid (I) and 2,5-diethyl-1H-pyrrol-1-yl-butanoic acid (V) were synthesised as non basic analogues of 4-aminobutanoic acid (GABA) to investigate the influence of the pKa of the 4-nitrogen on the in vitro binding to GABA receptors. (I) displaced 3H-GABA from specific binding sites of synaptosomal membrane preparations from rat cerebellum with an IC50 of 0.5 microM and (V) with an IC50 of 0.4 microM. (I) was inactive in vivo in the bicuculline anticonvulsant test (mice i.p.). The authors conclude that a basic nitrogen is not necessary for the binding to the GABAergic receptors although the ensuing complex is likely to be pharmacologically ineffective.

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