Antinociceptive and hypothermic effects of trimethyltin |
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Authors: | Lucio G Costa Shreenath V Doctor Sheldon D Murphy |
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Institution: | Division of Toxicology Department of Pharmacology University of Texas Medical School at Houston P.O. Box 20708 Houston, Texas 77025, USA |
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Abstract: | Trimethyltin (TMT) induced a dose-dependent antinociceptive and hypothermic effect in mice. Antinociception was not attenuated by naloxone but was reversed by atropine. TMT, however, was ineffective in displacing (3H)-QNB binding and did not affect (3H)-QNB binding or acetylcholinesterase activity after administration. The ethyl ester of nipecotic acid, a specific inhibitor of synaptosomal GABA uptake, exerted a similar antinociceptive effect that could be blocked by atropine. The GABA receptor antagonist bicuculline attenuated antinociception induced by TMT and nipecotic acid ethyl ester but not by morphine or oxotremorine. γ-Vinyl GABA, an irreversible inhibitor of GABA metabolism, prolonged TMT but not morphine-induced antinociception. In contrast, neither the dose-response nor the time course of TMT-induced hypothermia were affected by any of the drugs tested. The findings suggest that the GABAergic system may be involved in TMT induced antinociception; however, the mechanism responsible for the hypothermic effect of TMT is not apparent. |
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Keywords: | To whom correspondence should be addressed |
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