TCP (N-[1-(2-thienyl)cyclohexyl]
piperidine), A PCP (
phencyclidine) derivative, has been shown to possess
antiepileptic and neuroprotective efficacy against chemically induced
seizures. However, it is known that other antagonists of the
NMDA receptor impair spatial learning. This study was thus undertaken to explore the eventual effects of TCP on memory. The same study was done with
MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]-cyclohepten-5,10-
imine ), one of the most studied
NMDA receptor antagonists, which can be considered as a reference molecule. Three doses of each
drug were chosen: 0.05, 0.1, and 0.2 mg/kg for
MK-801 and 0.5, 1, and 2 mg/kg for TCP, the second dosage corresponding to the minimal required for antiseizure activity. The drugs were injected IP 30 min each day before a classical procedure of acquisition in a Morris water maze test. At the highest dose of each
drug, the animals did not learn the position of the platform. At 0.1 mg/kg
MK-801, the rats used a praxis strategy to find the platform but they did not known where the platform was. Contrary to
MK-801, TCP at 1 mg/kg did not induce any memory impairment. At the lowest doses used, no memory impairment was found. It thus appears that, at the minimal therapeutic dose effective against chemically induced
seizures (0.1 mg/kg for
MK-801 and 1 mg/kg for TCP), TCP, contrary to
MK-801, does not induce any memory impairment. Furthermore, at all the doses used, TCP presents the particularity that its locomotor side effects are not long lasting, being no longer observed from 30 min after the injection.