Abstract
Tests were made for interactions between antipsychotic drugs and compounds that enhance synaptic currents mediated by α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid-type glutamate receptors (“ampakines”). Typical and atypical antipsychotic drugs decreased methamphetamine-induced hyperactivity in rats; the effects of near or even subthreshold doses of the antipsychotics were greatly enhanced by the ampakines. Interactions between the ampakine CX516 and low doses of different antipsychotics were generally additive and often synergistic. The ampakine did not exacerbate neuroleptic-induced catalepsy, indicating that the interaction between the different pharmacological classes was selective. These results suggest that positive modulators of cortical glutamatergic systems may be useful adjuncts in treating schizophrenia.
Footnotes
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Send reprint requests to: Steven A. Johnson, Ph.D., Cortex Pharmaceuticals, Inc., 15231 Barranca Parkway, Irvine, CA 92618. E-mail: SJohnson{at}cortexpharm.com
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↵1 Present address: Department of Psychiatry, University of California, Irvine, CA 92717.
- Abbreviations:
- NMDA
- N-methyl-d-aspartate
- AMPA
- α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid
- LMA
- locomotor activity
- Received August 7, 1998.
- Accepted November 19, 1998.
- The American Society for Pharmacology and Experimental Therapeutics
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