Arzneimittelforschung 2007; 57(10): 625-632
DOI: 10.1055/s-0031-1296660
Editio Cantor Verlag Aulendorf (Germany)

Forty Years of Antipsychotic Drug Research – from Haloperidol to Paliperidone – with Dr. Paul Janssen

Frans H. L. Awouters
1  Waalse kaai 5, Antwerpen (Belgium
Paul J. Lewi
2  Catholic University Leuven (KUL), University Hospital, Leuven and Free University of Brussels (VUB), FABI, Brussels, Belgium
› Author Affiliations
Further Information

Publication History

Publication Date:
21 December 2011 (online)


The authors describe 40 years of antipsychotic drug research with Dr. Paul Janssen, which they have witnessed for a large part from first hand experience. The article describes the start of the Janssen Research and its early successes with antispasmodics and analgesics. The discovery of haloperidol followed from a serendipitous transition from analgesics to antip-sychotics and culminated with the historical International Symposium on Halo-peridol that was held in Beerse (Belgium) in 1959. The concept of the central role of dopamine receptor binding in schizophrenia has played a decisive part in focusing the Janssen Research on antipsy-chotics. Paul Janssen did not rest with haloperidol (CAS 52-68-8), but expanded it into the family of butyrophenone an-tipsychotics, using Haase‧s handwriting test to clinically characterize the analogues. The emerging significance of serotonin antagonism in schizophrenia is discussed in the light of the discovery of pi-pamperone (CAS 1893-33-0), a forerunner of the modern so-called atypical neu-roleptics. Continued research produced a novel chemical family of neuroleptics, exemplified by pimozide (CAS 2062-78-4) and fluspirilene (CAS 1841-19-6), and yielded selective serotonin 5HT2-antago-nists. This research ultimately led to the discovery of risperidone (CAS 106266-06-2) and paliperidone (CAS 144598-75-4), compounds with inbuilt dopamine and serotonin antagonism. The authors discuss the lack of inhibition as a common trait of stereotyped behaviour in schizophrenia and the means of determining it by means of a computerized version of Bente’s button press test. Finally the appropriate use of antipsychotics for optimal therapeutic result with minimal side effects is advocated.