Binding properties of [H-3]gacyclidine in the rat central nervous system

Gacyclidine (1-[1-(2-thienyl)-2-methylcyclohexyl]piperdine), the racemate o f (+)-and (-)-GK11, exhibits potent neuroprotective properties due to its a ntagonism at the NMDA receptor. In its tritiated form, gacyclidine showed a binding distribution similar to that of NMDA receptors in the rat brain. W ith membrane preparations, the (-)-enantiomer of gacyclidine exhibited an a ffinity similar to that of MK-801 (dizocilpine, (+)-5-methyl-10,11-dihydro- 5H-dibenzo[a, d]cyclohepten-5,10-imine) in the low nanomolar range, while t he (+)-enantiomer was about 10 times less potent. Gacyclidine affinity was lower in the cerebellum than in the forebrain or the spinal cord. In this l atter region and in the cerebellum, two binding sites were evidenced, one o f which was a low-affinity site insensitive to MK-801. In all regions, PRE- 084 (2-(4-molpholino)ethyl-1-phenylcyclohexane-1-carboxylate), a sigma rece ptor ligand, had no effect on [H-3]gacyclidine binding. (C) 2000 Elsevier S cience B.V. All rights reserved.