The muscle relaxant thiocolchicoside is an antagonist of GABAA receptor function in the central nervous system
Neuropharmacology. 2006-09-01; 51(4): 805-815
DOI: 10.1016/j.neuropharm.2006.05.023
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1. Neuropharmacology. 2006 Sep;51(4):805-15. Epub 2006 Jun 30.
The muscle relaxant thiocolchicoside is an antagonist of GABAA receptor function
in the central nervous system.
Carta M(1), Murru L, Botta P, Talani G, Sechi G, De Riu P, Sanna E, Biggio G.
Author information:
(1)Department of Experimental Biology Bernardo Loddo, Section of Neuroscience,
University of Cagliari, Cittadella Universitaria, SS 554, Km 4.5, Monserrato,
Cagliari 09123, Italy.
Thiocolchicoside (TCC) is used clinically for its muscle relaxant,
anti-inflammatory, and analgesic properties, and it has been shown to interact
with gamma-aminobutyric acid (GABA) type A receptors (GABAARs) and
strychnine-sensitive glycine receptors in the rat central nervous system. In
contrast to a proposed agonistic action at these two types of inhibitory
receptors, pharmacological evidence has shown that, under certain conditions, TCC
manifests convulsant activity in animals and humans. We now show that the phasic
and tonic GABAAR-mediated currents recorded from Purkinje cells and granule
neurons, respectively, in parasagittal cerebellar slices from adult male rats
were inhibited by TCC in a concentration-dependent manner. The median inhibitory
concentrations of TCC for these effects were approximately 0.15 and approximately
0.9 microM, respectively. TCC did not potentiate GABABR-mediated currents in
hippocampal slices, suggesting that its muscle relaxant action is not mediated by
GABABRs. Intraperitoneal injection of TCC in rats either alone or in combination
with negative modulators of GABAergic transmission revealed convulsant and
proconvulsant actions of this drug. Our data, consistent with clinical
observations of the epileptogenic effect of this compound, suggest that TCC is a
potent competitive antagonist of GABAAR function.
DOI: 10.1016/j.neuropharm.2006.05.023
PMID: 16806306 [Indexed for MEDLINE]