13 BTS 54 524-an Approach to a Rapidly Acting Antidepressant W. R. Buckett, G. P. Luscombe and P. C. Thomas 13.1 Introduction Since the tricyclic antidepressant drugs were first introduced into therapy, con- sistent efforts have been made to improve upon their effects in terms of both increased efficacy and reduced side-effects (Hollister, 1986). In addition, anti- depressants having various degrees of selectivity for different monoamine systems (e.g. maprotiline for selective inhibition of noradrenaline reuptake, and fluvox- amine for selective inhibition of serotonin reuptake) have been introduced in the belief that they may treat various subgroups of depressive patients. Overall, however, the wide-spectrum monoamine uptake inhibitors such as dothiepin, imipramine and amitriptyline still remain the most widely used drugs for the treatment of depression, with more recent drugs such as trazodone and mianserin (Ostrow, 1985) also gaining a place on the basis of improvements in tolerability. However, there are still important objectives through which advances in drug therapy of depression can be expected. First, the speed of onset of antidepressant drugs could be increased, and, second, the efficacy could be also improved in the hope of treating, with novel pharmacological agents, those patients currently referred for electroconvulsive therapy. Preclinical studies with BTS 54 524 (N-1-(1-(4-chlorophenyl)cyclobutyl)-3- methylbutyl-N,N-dimethylamine hydrochloride monohydrate), a novel structural type of putative antidepressant (Fig. 13.1), have suggested that these objectives might be met in clinical practice. M. Briley et al. (eds.), New Concepts in Depression © The Editors and the Contributors 1988