Common molecular features in antipsychotic drugs and the topography of their binding site

Abstract

Four classes of compounds are in general use for treating psychotic patients, namely phenothiazines, thioxanthenes, butyrophenones and benzamides. Recent findings suggest that therapeutic effects of antipsychotic drugs may be due to actions at a particular binding site. It is possible, therefore, that antipsychotic drugs have common structural features which permit them to interact with a common binding site. Many models concerning crucial molecular features in antipsychotic drugs view those compounds in 'stretched-out' conformations. It is important to note, however, that antipsychotic drugs will be surrounded by water molecules in the body, which may cause them to have 'curled-up' conformations. Using a trial-and-error approach and educated guessing, I have re-viewed possible conformations of antipsychotic drugs in an effort to find common spatial features between them. I have arrived at some computer-graphic models of antipsychotics in 'curled-up' conformations that may describe common spatial features. My studies have led to a tentative topographical model for the binding site consisting of four areas. My model may provide a means for rationalizing the common effects of the four major classes of antipsychotic drugs.

Key Words:

• ntipsychotic
• neuroleptic
• psychotropic drug
• receptor model
• stereoisomer