Advertisement

Psychopharmacology

, Volume 129, Issue 4, pp 299–310 | Cite as

Cocaine-induced convulsions: pharmacological antagonism at serotonergic, muscarinic and sigma receptors

  • M. C. Ritz
  • Frank R. George
ORIGINAL INVESTIGATION

Abstract

The concurrent influence of multiple neurotransmitter systems in mediating cocaine-induced convulsions is predicted by the results of previous receptor binding studies. The present results demonstrate that pharmacological manipulations of these predicted neurotransmitter systems alters the occurrence of cocaine-induced convulsions. The 5-HT reuptake inhibitor fluoxetine enhanced the occurrence and severity of convulsions produced by 100 mg/kg (−) cocaine, while the 5-HT2 receptor antagonists cinanserin, ketanserin and pirenperone antagonized cocaine-induced convulsions in a dose-dependent manner. Further, the M1 receptor antagonist pirenzepine antagonized cocaine-induced convulsions, but atropine did not. In addition, both the (+) and (−) stereoisomers of the sigma ligand SKF 10047 significantly attenuated cocaine-induced convulsions. (+)SKF 10047 was more potent than (−)SKF 10047 in this effect, suggesting a stereoselective effect at sigma receptor sites. In contrast, DA and NE neurotransmission do not appear to modulate the proconvulsant effects of cocaine in a specific, dose-dependent manner. Thus, of the CNS binding sites with which cocaine is known to interact, the results are consistent with the conclusion that 5-HT transporters and 5-HT2 receptor sites appear to be direct and primary sites related to cocaine-induced convulsions, while M1 and sigma binding sites appear to play important but secondary and modulatory roles in this response.

Key words Cocaine Convulsions Dopamine Norepinephrine Serotonin Sigma Muscarinic 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Copyright information

© Springer-Verlag Berlin Heidelberg 1997

Authors and Affiliations

  • M. C. Ritz
    • 1
  • Frank R. George
    • 1
  1. 1.Amethyst Technologies, Inc., 1435 North Hayden Road, Scottsdale, AZ 85257-3773, USA FAX (+1) 602/970-6355, e-mail: ritzmc@aol.comUS

Personalised recommendations