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The synthesis of 5H-imidazo [2,1-c] [1,4] benzodiazepine derivatives is described. Hydroxymethylation of 1-(2-nitrobenzyl)imidazoles by reaction with formaldehyde in a sealed tube and subsequent oxidation of hydroxymethylimidazoles with activated manganese dioxide afforded 1-(2-nitrobenzyl)imidazole-2-carboxaldehydes. The latter compounds were treated with iron(II) sulphate to yield directly the expected tricyclic imidazobenzodiazepines by intramolecular cyclization of the intermediates aminoaldehydes. The tricyclic derivatives were subjected to pharmacological screening to evaluate the effects on the behavior of the animals and the interaction with some biogenic amines. Some of the tested compounds were comparable to chlordiazepoxide in sedative and muscle-relaxant activities. None of them showed antiserotonin, anticholinergic or adrenolytic activities.

Although more than twenty-five years of clinical use and several placebo-controlled studies have demonstrated the clinical effectiveness of anti-depressant drugs, the mechanism through which these drugs function and how they relate to the pathological mechanisms that underlie depressive disorders are still not clear. The present article briefly reviews the literature available on the subject. In chronological order, it examines studies on the clinical effectiveness of antidepressants, their effects on biogenic amine metabolism and on known receptor systems. The existence of possible specific receptor systems for tricyclic anti-depressants, their modifications during depressive illness, the effect of treatment with psychotropic drugs and the role which these systems may play in depression are then illustrated.