The neuroleptics: a historical survey

The history of the neuroleptic drugs has been marked by various milestones: some have been successes, others have been associated with complications and side effects, especially when the drugs have been misused. At the Paris meeting in 1955, it was confirmed that neuroleptics were indicated in chronic psychoses. In 1963, a new form of long-acting neuroleptic was introduced which appeared useful for non-compliant patients. However, following the introduction of the American concept of "CPZ- equivalent" which is opposed to the European distinction between sedative and "disinhibitory" neuroleptics, the problem of the development of tardive dyskinesia became serious. The antipsychotic actions of the neuroleptics in some psychoses eventually led to the so-called "dopaminergic theories" of schizophrenia, which are still under discussion. It should be underlined that the specific antimanic action of neuroleptics, which is included in the early definition, has been prematurely neglected. In fact, mania is the opposite of depression and, in general, the antidepressants are "anti-neuroleptic". The neurobiological studies of the neuroleptics resulted in the differentiation of the compounds according to their action on different parts of the dopamine system, especially on the mesolimbic and mesocortical structures. This was particularly useful in the efforts to avoid extrapyramidal side effects. The clarification of the role of the D1 and D2 dopamine receptors has been important in understanding the development of tardive dyskinesias. There are now some 50 different neuroleptic drugs, in about a dozen chemical families, which can be classified by an "automatic" statistical method.