MONOAMINERGIC SYNAPSES AND SCHIZOPHRENIA - 45 YEARS OF NEUROLEPTICS

In 1952 Delay and Deniker introduced the first antipsychotic, chlorpro mazine, into the treatment of mental patients. They subsequently defin ed the word 'neuroleptic' to describe drugs as different as reserpine and chlorpromazine which seemed to have similar effects on the mental life of patients. In the 1960s the hypothesis was developed, mainly du e to Carlsson, that the principal mode of action of neuroleptics was t o interfere with synaptic transmission mediated by dopamine (DA) in th e brain. This concept was given substantial credence with the discover y by Seeman and Snyder in the 1970s that many of the neuroleptics acte d as DA receptor blockers. Subsequently two different classes of DA re ceptor were defined on the basis of their coupling to adenylate cyclas e by Kebabian. In the 1980s molecular biology led to the cloning of fi ve different DA receptors, and at the end of this period van Tol and h is colleagues cloned the Dq DA receptor, which has been of considerabl e interest in the 1990s as it is greatly elevated in the brains of sch izophrenics. This historical review ends with a consideration of the p ossibility that in addition to DA receptors, serotonin and perhaps oth er transmitter receptors are involved in the aetiology of schizophreni a.