THE identification and characterisation of stereospecific, high-affinity binding sites for benzodiazepines in the mammalian CNS has been described both in vivo1-3 and in vitro4-6. The correlations obtained between the in vitro affinities of a series of benzodiazepines for these binding sites and their clinical potencies as muscle relaxants2, anxiolytics6 and anticonvulsants6 strongly suggest that these sites are pharmacological receptors mediating the therapeutic actions of the benzodiazepines. Benzodiazepines such as clonazepam, oxazepam and flurazepam are rapidly reversible, competitive inhibitors of 3H-diazepam binding to synaptosomal membranes7,8. Competitive inhibition of 3H-diazepam binding has also been observed with the triazolopyridazines, which possess both anticonvulsant and anxiolytic activity9, and with the purines inosine and hypoxanthine 10,11, which may be endogenous ligands to the benzodiazepine receptor10-14. The development of noncompetitive, irreversible ligands has been invaluable in the characterisation, isolation and purification of both peripheral and central neurotransmitter receptors15, and may also prove useful for studying the benzodiazepine receptor. We now report the synthesis of a novel benzodiazepine, irazepine, which acts as a noncompetitive, irreversible inhibitor of 3H-diazepam binding to synaptosomal membranes.