INTERACTIONS OF ANXIOLYTIC DRUGS WITH BENZODIAZEPINE RECEPTORS

Abstract

ABSTRACT Brain specific benzodiazepine (BZ) receptors are allosterically modulated by other compounds which are structurally not related to BZs. Thus, stimulation by GABA and by GABA analogues of BZ receptor binding exhibits the pharmacological characteristics of a GABA receptor suggesting that BZ binding sites are constituents of a GABA/BZ receptor complex. In addition, BZ receptor binding is modulated by a number of other compounds which act at a site closely related to GABA receptor-associated chloride channels. These compounds include certain anions, picrotoxin, IPTBO and pyrazolopyridines. The modulatory actions of pyrazolopyridines, drugs with anxiolytic-like actions, include stimulatory effects on both GABA and BZ binding sites. Both stimulatory actions are similarly anion-dependent, sensitive to Triton-X 100 and appear to be restricted to a subgroup of BZ receptors, the GABA/BZ-P51receptor complex, which is present to a varying extent in all brain regions examined. Binding of BZs to this receptor type is preferentially inhibited by the anxiolytic triazolopyridazine CL 218,872. These observations suggest molecular and pharmacological heterogeneity of GABA and BZ receptors in brain.