Purines as endogenous ligands of the benzodiazepine receptor.

Endogenous inhibitors of [3H]benzodiazepine binding have been isolated from the mammalian central nervous system and identified as the purines inosine and hypoxanthine. The affinities of these compounds for the benzodiazepine receptor are many orders of magnitude lower than those reported for clinically effective benzodiazepines. However, the enhanced formation of these compounds, which occurs during electrical or chemical depolarization of brain tissue, coupled with the small number of receptors that must be occupied to manifest the pharmacologic effects of benzodiazepines in vivo are consistent with a purinergic modulation of the benzodiazepine receptor. The pharmacologic, electrophysiologic, and neurochemical observations presented in this review further support either a neurotransmitter or neuromodulatory role of purines in the function of the benzodiazepine receptor.