Albin_1988_Neurosci.Lett_88_303

The effect of tetrahydro-9-aminoacridine (THA) and related compounds on ligand binding to the dissociative anesthetic (phencyclidine, PCP) receptor site was assessed using a rat brain homogenate assay. THA displaced the dissociative anesthetic ligand [3H]N-(1-[2-thienyl]cyclohexyl)3-4-piperidine [( 3H]TCP) binding with an IC50 of 26 microM. Other acridine derivatives displayed similar potency as displacers of [3H]TCP. Cholinesterase inhibitors and aminopyridines had IC50s equal to or greater than 100 microM. Saturation studies of [3H]TCP in the presence and absence of 30 microM THA revealed competitive inhibition with a K1 of 15 microM. The clinical pharmacology of THA suggests that it antagonizes the effects of dissociative anesthetics whereas in vitro, it behaves as a weak PCP agonist. THA may exert some of its clinical effects through interaction with the PCP receptor, and may have mixed agonist-antagonist properties.