Tetrahydro-9-aminoacridine (THA) interacts with the phencyclidine (PCP) receptor site.
R L Albin, A B Young, J B Penney
Neuroscience Letters June 7, 1988 DOI: 10.1016/0304-3940(88)90228-5 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | In vitro receptor binding study Peer reviewed |
|---|---|
| Population | Rat brain homogenate |
| Interventions | Tetrahydro-9-aminoacridine (THA) acridine derivatives cholinesterase inhibitors aminopyridines |
| Dose | 30 microM THA |
| Measures | [3H]TCP binding, IC50, Ki |
| Key points | THA displaced [3H]TCP binding to the PCP receptor with an IC50 of 26 microM and competitively inhibited binding with a Ki of 15 microM; other acridine derivatives were similarly potent, whereas cholinesterase inhibitors and aminopyridines had IC50s of at least 100 microM. The authors propose that THA acts in vitro as a weak PCP agonist despite clinical evidence of antagonizing dissociative anesthetics, suggesting mixed agonist-antagonist properties. |
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.