LIMITATIONS OF THE BENZODIAZEPINE RECEPTOR NOMENCLATURE: A PROPOSAL FOR A PHARMACOLOGICAL CLASSIFICATION AS OMEGA RECEPTOR SUBTYPES

Abstract

Summary— At present, the nomenclature of benzodiazepine (BZ) receptors is based on historical association with the BZ structure. However, it is mainly through the new compounds chemically unrelated to BZ that the central and peripheral subtypes of BZ receptors have been characterized. We therefore propose the nomenclature of a Greek letter omega, as ω₁, ω₂, and ω₃ to designate the central BZ₁, BZ₂, and peripheral BZ receptors, respectively. Among the several classes of non-BZD drugs with affinity for different receptors, the imidazopyridines provide a valuable tool for the characterization of omega receptor subtypes. Most BZ are nonselective ligands for the central ω₁ and ω₂ receptors, while selectivity for ω₁ receptor subtypes is present in several non BZ chemical series: imidazopyridines (zolpidem), triazolopyridazines (CL 218872), betacarbolines (β-CCE), and pyrazoloquinolines (CGS 8216). Selective ligands for the ω₂ subtype are not available so far. The so-called peripheral BZ receptor is also present in the central nervous system; therefore, the proposed nomenclature of ω₃ receptors resolves this paradox because it does not designate location and is defined in terms of pharmacological specificity. Selective ligands for ω₃ receptors include the BZ Ro 5–4864, and the isoquinolinecarboxamide PK 11195, while the imidazopyridine alpidem is the ligand with the highest affinity for this receptor subtype.