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®, 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.