ObjectiveThis article provides the chemical basis for the molecular modification of H1antihistamines in the rational development of some antidepressant and antipsychotic drugs.MethodsA review of the literature and personal experiences have been compiled.ConclusionsThe contributions of many basic scientists, the crucial observations of clinicians, and the desire of the drug industry to make money have resulted in the currently available psychopharmacological treatments. The future development of psychopharmacology depends on better clinical research to generate new hypotheses of the chemical and behavioral pathology of mental disease. Psychosomatic medicine can make a unique contribution in its interdisciplinary role of stressing brain, body, and mind relationships.