History of the dopamine hypothesis of antipsychotic action  

作　　者：Mary V Seeman 

机构地区：[1]Department of Psychiatry,University of Toronto,Toronto M5P 3L6,Ontario,Canada

出　　处：《World Journal of Psychiatry》2021年第7期355-364,共10页世界精神病学杂志

摘　　要：The dopamine hypothesis of how antipsychotic drugs exert their beneficial effect in psychotic illness has an interesting history that dates back to 1950.This hypothesis is not to be confused with the dopamine hypothesis of schizophrenia;the aim of the latter is to explain the etiology of schizophrenia.The present review does not deal with schizophrenia but,rather,with the historical development of our current understanding of the dopamine-associated actions of the drugs that reduce the symptoms of psychosis.This historical review begins with the serendipitous discovery of chlorpromazine,a drug synthesized around a chemical core that initially served to produce man-made dyes.This molecular core subsequently contributed to the chemistry of antihistamines.It was with the aim of producing a superior antihistamine that chlorpromazine was synthesized;instead,it revolutionized the treatment of psychosis.The first hypothesis of how this drug worked was that it induced hypothermia,a cooling of the body that led to a tranquilization of the mind.The new,at the time,discoveries of the presence of chemical transmitters in the brain soon steered investigations away from a temperature-related hypothesis toward questioning how this drug,and other drugs with similar properties and effects,modulated endogenous neurotransmission.As a result,over the years,researchers from around the world have begun to progressively learn what antipsychotic drugs do in the brain.

关 键 词：CHLORPROMAZINE HALOPERIDOL G-Protein coupled receptors Binding assays Receptor imaging High affinity states 

分 类 号：R749[医药卫生—神经病学与精神病学]