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
antipsychotics and culminated with the historical International Symposium on
Haloperidol 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
antipsychotics. Paul Janssen did not rest with
haloperidol (CAS 52-68-8), but expanded it into the family of butyrophenone
antipsychotics, 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
pipamperone (CAS 1893-33-0), a forerunner of the modern so-called atypical
neuroleptics. 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-antagonists. 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.