Publisher Summary This chapter summarizes the nature of the benzodiazepine receptor that has been characterized further, by the demonstration that a single class of binding sites exists in rat brain for a structurally diverse series of benzodiazepines. It has been found that gamma-aminobutyric acid (GABA) or the GABA-agonist muscimol cause an increase in the affinity of H-D for its binding site that is markedly dependent on the presence of NaCl, while the GABA-antagonist bicuculline decreased affinity. Inosine and hypoxanthine have been identified as endogenous ligands for H-D binding sites in bovine brain, as has a heat-stable protein of M.W.>15,000 isolated from rat brain. Halazepam in controlled clinical studies has been shown to be an effective anxiolytic agent at 40-600mg/day with relatively minor side effects. Sleep laboratory studies with benzodiazepines have defined the phenomenon of “rebound insomnia” that occurs on abrupt withdrawal of drug. This phenomenon seems to be associated only with the short-acting triazolam, flunitrazepam, and nitrazepam, but not with the longer acting flurazepam or diazepam. The 4-hydroxylated metabolites of triazolam and alprazolam possess a low order of anticonvulsant activity in contrast to the hydroxylated metabolites of diazepam. Fenobam, that had a pharmacological profile in animals indicative of anxiolysis, showed EEG effects in man more typical of psychostimulants. The sedative-antihistamine trimeperazine at 20mg has been inferior to nitrazepam (5mg) as a sleep inducer in a double-blind study. Clinical trials indicate that zopiclone is useful as a hypnotic and is as active as nitrazepam.