The consolidation of neuroleptic therapy: Janssen, the discovery of haloperidol and its introduction into clinical practice.

The discovery of haloperidol at the end of the 1950s constitutes one of the greatest advances of 20th century psychiatry. This antipsychotic drug has their origin in the research process of central analgesic molecules derived from pethidine and methadone, carried out by the Belgian company Janssen Phamaceutica. After the synthesis of phenoperidine, numerous analogues of this compound were studied, and chemists at Janssen took the decision to substitute the propiophenone group for a butyrophenone group. One of these compounds went the R-1625, a stronger agent with specifically neuroleptic properties but lacking morphine-like activity. This substance was synthesized on the 11th February 1958 and received the generic name of haloperidol because of the two halogenated substitutes incorporated into the molecule. Clinical development of haloperidol was conducted, primarily, by psychiatric research team at the University of Liège that confirmed its efficacy in the treatment of various psychiatric disorders such as acute and chronic paranoid psychosis, mania, or chronic treatment-resistant schizophrenia. Under the brand name Haldol((R)), haloperidol was licensed and marketed in Belgium in October 1959. The direct and differed consequences of its introduction into the psychiatric practice have been multiple, involving different areas of socio-sanitary reality. Moreover, haloperidol has contributed substantially to the development of biological psychiatry and currently neuroscience, because it made possible the development of new experimental models for predicting the effects of antipsychotics, and allowed the postulate of the firsts biological hypotheses about the schizophrenia etiology. Haloperidol has been included in the World Health Organisation's list of essential medicines.

The haloperidol story.

Haloperidol was synthesized on the 11th of February 1958 at the Janssen Laboratories, in Belgium. Soon after its synthesis and animal studies, which suggested to Paul Janssen and his colleagues that this butyrophenone drug would be of great interest as its action was similar but much more powerful than that of chlorpromazine, haloperidol was administered to humans at the Liege hospital. The subsequent clinical studies confirmed that this new drug was particularly active against delusions and hallucinations. The introduction of haloperidol in the United States of America was difficult for clinical and legal reasons. For many years, haloperidol had been widely used in western countries, until the introduction of "new antipsychotics."

Cinqüenta anos de medicamentos antipsicóticos em psiquiatria: III. fenotiazinas piperidínicas / Fifty years of antipsychotic drugs in psychiatry: III. piperidine phenothiazines

Na iminência de uma nova era na terapêutica psiquiátrica com a redescoberta da clozapina e a introduçäo dos novos antipsicóticos atípicos, é tempo de um inventário das substâncias desenvolvidas nos últimos cinqüenta anos. É feito um breve histórico dos antecedentes dos antipsicóticos tradicionais na era que se encerra. As substâncias introduzidas até o presente poderiam ser reunidas nos grupos tradicionais - fenotiazinas (alifáticas, piperazínicas e piperidínicas), tioxantenos, butirofenonas, difenilbutilpiperidinas, benzaminas, indóis, dibenzoxazepinas - e nos grupos químicos mais recentes - diidroindolonas, dbenzodiazepinas, benzisoxazólicos -, além de compostos ainda em desenvolvimento. Neste artigo, o terceiro de uma série concebida com esta finalidade, säo examinados os derivados fenotiazínicos com cadeia lateral piperidínica que tenham demonstrado utilidade na prática clínica e ou guardem importância histórica: mepazina, mesoridazina, nortioridazina, piperacetazina, propericiazina, sulforidazina e toridazina. Com base em bibliografia básica específica, säo discutidos aspectos técnicos e revisado o conhecimento científico acumulado através da experimentaçäo e utilizaçäo clínica destes compostos, desde seu lançamento até a presente data, com informaçöes sistemáticas sobre fórmula estrutural, fórmula molecular, nomes químicos, nomes de fantasia e códigos de cada composto, além de dados sobre eventual comercializaçäo no país

Historias de las butirofenonas / History of butyrophenones

Se relata cómo ocurrió el hallazgo de la fórmula de las butirofenonas y la síntesis de la droga "R-1625"' que se denominó después haloperidol. Se hace una breve descripción de su difusión en Europa y las dificultades que surgieron cuando se usó por primera vez en Norteamérica. Se describen sus principales propiedades y efectos secundarios y se trata, además, de dos derivados difenilpiperidínicos: el fluspirileno y la pimocida

Historias de las butirofenonas / History of butyrophenones

Se relata cómo ocurrió el hallazgo de la fórmula de las butirofenonas y la síntesis de la droga "R-1625"' que se denominó después haloperidol. Se hace una breve descripción de su difusión en Europa y las dificultades que surgieron cuando se usó por primera vez en Norteamérica. Se describen sus principales propiedades y efectos secundarios y se trata, además, de dos derivados difenilpiperidínicos: el fluspirileno y la pimocida