The solid state conformations and absolute configurations of the antidepressant alaproclate and two potentially neuroleptic rigid spiro amines have been determined by X-ray crystallographic techniques.

Alaproclate is a selective inhibitor of neuronal 5-hydroxytryptamine (5-HT) reuptake. Charge distribution and energy calculations have been performed for alaproclate and 5“HT in order to ascertain the structural and conformational features of these compounds at the molecular level, in particular when interacting with the carrier site on the presynaptic side of the nerve endings. The conformational features of some other selective 5-HT reuptake inhibitors and' the complementary properties of the carrier site are also discussed.

The two potentially neuroleptic rigid spiro amines show stereoselective dopamine-receptor-blocking capabilities. Geometrical parameters intended to describe the conformation have been calculated for the two spiro amines as well as for some other stereoselective neuroleptics displaying a rather high degree of rigidity. Molecular mechanisms proposed to explain the dopamine-receptor-blocking capability of the neuroleptics are discussed. A comparative study concerning structural similarities between dopamine and several neuroleptics is also presented.