Effects Of Linopirdine, Hp-749, And Glycyl-Prolyl-Glutamate On Transmitter Release And Uptake

Linopirdine, HP 749, and glycyl-prolyl-glutamate (GPE) are compounds that have been reported to alter the release of neurotransmitters. This study compares the potassium-stimulated neurotransmitter release enhancing properties of these compounds in parallel. While not affecting the apparent release of [H-3]norepinephrine ([H-3]NE), linopirdine at a concentration of 10 muM enhanced the potassium evoked release of cerebral 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 processes, since the drug did not inhibit neurotransmitter uptake at the concentration (10 muM) which caused maximal release enhancement. HP 749 increased 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 inhibitor 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. GPE was devoid of release enhancing activity under the conditions used in the present study. (C) 1993 Wiley-Liss, Inc.