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Vol. 289, Issue 1, 392-397, April 1999

Synergistic Interactions between Ampakines and Antipsychotic Drugs

Steven A. Johnson, Nguyen T. Luu, Todd A. Herbst, Richard Knapp, David Lutz, Amy Arai1, Gary A. Rogers and Gary Lynch1

Cortex Pharmaceuticals, Incorportated, Irvine, California

Tests were made for interactions between antipsychotic drugs and compounds that enhance synaptic currents mediated by alpha -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.

0022-3565/99/2891-0392$03.00/0
THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Copyright © 1999 by The American Society for Pharmacology and Experimental Therapeutics


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Copyright © 1999 by the American Society for Pharmacology and Experimental Therapeutics.