title: Tetrahydro-9-aminoacridine (THA) interacts with the phencyclidine (PCP) receptor site.
abstract: 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.
authors.affiliation: Department of Neurology, University of Michigan, Ann Arbor 48104.
authors.forename: R L
authors.initials: RL
authors.lastname: Albin
authors.forename: A B
authors.initials: AB
authors.lastname: Young
authors.forename: J B
authors.initials: JB
authors.lastname: Penney
mesh_terms: D000166:Acridines / Q000378:metabolism; D000609:Aminoacridines / Q000378:metabolism*; D000631:Aminopyridines / Q000378:metabolism; D000818:Animals; D001667:Binding, Competitive; D002800:Cholinesterase Inhibitors / Q000378:metabolism; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D010622:Phencyclidine / Q000031:analogs & derivatives / Q000378:metabolism; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000378:metabolism*; D017478:Receptors, Phencyclidine; D013619:Tacrine / Q000378:metabolism*
chemical_list: D000166:Acridines; D000609:Aminoacridines; D000631:Aminopyridines; D002800:Cholinesterase Inhibitors; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D017478:Receptors, Phencyclidine; D013619:Tacrine; C012058:tenocyclidine; D010622:Phencyclidine