Synergistic Anticonvulsant Effects of GABA-T Inhibitors and Glycine

Overview

Journal Naunyn Schmiedebergs Arch Pharmacol

Specialty Pharmacology

Date 1984 May 1

PMID 6472485

Citations 5

Authors

N Seiler

S Sarhan

Affiliations

Soon will be listed here.

Abstract

The anticonvulsant effect of inhibitors of GABA-T (R/S-gamma-vinyl-GABA, ethanolamine-O-sulfate, gabaculine, aminooxyacetic acid) was enhanced by 10 mmol/kg glycine in animal seizure models which are based on a functional GABA deficit. Similar to glycine in their action, although less effective, were its close structural analogues (sarcosine, N,N-dimethylglycine) and homologous omega-aminoacids (beta-alanine, taurine, gamma-aminobutyric acid, delta-aminovaleric acid). It is assumed that glycine and its structural analogues act on supraspinal glycine receptors as glycine agonists. Our observation is the first example of the synergistic interaction of two inhibitory neuronal systems resulting in the amplification of the anticonvulsant effect. Combined treatment with GABA-T inhibitors and glycine may turn out to be of practical importance in the therapy of seizure disorders and other diseases, for which treatment with GABA-T inhibitors is considered a potentially useful therapeutic approach.

Citing Articles

Effects of inhibition of ornithine aminotransferase on thioacetamide-induced hepatogenic encephalopathy.

Sarhan S, Knodgen B, Grauffel C, Seiler N Neurochem Res. 1993; 18(4):539-49.

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Antagonism of phencyclidine-induced hyperactivity by glycine in mice.

Toth E, Lajtha A Neurochem Res. 1986; 11(3):393-400.

PMID: 3703107 DOI: 10.1007/BF00965013.

Acute and chronic effects of lithium chloride on GABA-ergic function in the rat corpus striatum and frontal cerebral cortex.

Otero Losada M, Rubio M Naunyn Schmiedebergs Arch Pharmacol. 1986; 332(2):169-72.

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(4S)-4-amino-5,6-heptadienoic acid (MDL 72483): a potent anticonvulsant GABA-T inhibitor.

Sarhan S, Casara P, Knodgen B, Seiler N Neurochem Res. 1991; 16(3):285-93.

PMID: 1780030 DOI: 10.1007/BF00966092.

Alterations of GABA metabolism and seizure susceptibility in the substantia nigra of the kindled rat acclimating to changes in osmotic state.

Baxter C, Oh C, Wasterlain C, Ozaki L, Baldwin R Neurochem Res. 1991; 16(3):269-78.

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