Theoretical studies on tricyclic antidepressants. I. Molecular structures

Tricyclic antidepressants are believed to act by inhibiting reuptake of biogenic amines into the presynaptic neuron. This fundamental information can be exploited to characterize the reuptake mechanism in detail and to suggest modifications in drug structure aimed at improving therapeutic value. Knowledge of the three-dimensional geometry of tricyclic antidepressants is a prerequisite for such a research. Hence generation of possible geometries for such structures by theoretical and computer simulation methods has been attempted. Only a limited number of reasonable structures were obtained for most of the molecules, indicating that the obtained structures are likely to be close to actual structures. This has been somewhat substantiated by a study on the structure of imipramine hydrochloride by X-ray crystallographic methods.