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

Gacyclidine (1-[1-(2-thienyl)-2-methylcyclohexyl]piperidine), the racemate of (+)-and (-)-GK11, exhibits potent neuroprotective properties due to its antagonism at the NMDA receptor. In its tritiated form, gacyclidine showed a binding distribution similar to that of NMDA receptors in the rat brain. With membrane preparations, the (-)-enantiomer of gacyclidine exhibited an affinity 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 the (+)-enantiomer was about 10 times less potent. Gacyclidine affinity was lower in the cerebellum than in the forebrain or the spinal cord. In this latter region and in the cerebellum, two binding sites were evidenced, one of which was a low-affinity site insensitive to MK-801. In all regions, PRE-084 (2-(4-morpholino)ethyl-1-phenylcyclohexane-1-carboxylate), a sigma receptor ligand, had no effect on [3H]gacyclidine binding.