EFFECTS OF LINOPIRDINE, HP-749, AND GLYCYL-PROLYL-GLUTAMATE ON TRANSMITTER RELEASE AND UPTAKE

Linopirdine, HP 749, and glycyl-prolyl-glutamate (GPE) are compounds t hat have been reported to alter the release of neurotransmitters. This study compares the potassium-stimulated neurotransmitter release enha ncing properties of these compounds in parallel. While not affecting t he apparent release of [H-3]norepinephrine ([H-3]NE), linopirdine at a concentration of 10 muM enhanced the potassium evoked release of cere bral cortical and hippocampal [H-3]acetylcholine ([H-3]ACh) release by 143% and 200% over control, respectively, and striatal [H-3]dopamine ([H-3]DA) and hippocampal [H-3]d-aspartate ([H-3]d-Asp) release by 236 % and 65% over control, respectively. The release enhancing effects of linopirdine were not due to inhibition of high-affinity uptake proces ses, since the drug did not inhibit neurotransmitter uptake at the con centration (10 muM) which caused maximal release enhancement. HP 749 i ncreased the extracellular concentrations of the catecholamines, [H-3] NE and [H-3]DA, but not [H-3]ACh or [H-3]d-Asp. HP 749 was a potent in hibitor of both [H-3]NE and [H-3]DA uptake, and this may, in part, be responsible for the apparent release enhancing activity of the drug. G PE was devoid of release enhancing activity under the conditions used in the present study. (C) 1993 Wiley-Liss, Inc.