In 1891, Paul Ehrlich began investigating the possible antimalarial effects of methylene blue. His studies prompted other such studies with antimalarials, including phenothiazine analogues of the dye. One of these analogues, fenethazine, was found to be a potent antihistamine, and was well received by clinicians as an antiallergic drug. Homologues of fenethazine, although found to be weak antihistamines, had pronounced anticholinergic effects and were used successfully in the treatment of Parkinson's disease. Henri Laborit's search to find a drug that would be of value in preventing the traumatic consequences of shock caused by circulatory collapse during surgery led him to discover the important effects that antihistamines, particularly promethazine, had on the central nervous system. Investigations of centrally acting phenothiazines suitable to Laborit's requirements, with more sedating properties, eventually led to the development of chlorpromazine and its use as an antipsychotic drug. (C) 2002 Prous Science. All rights reserved.
