The Goodness of Side Effects

The discovery and subsequent development of antipsychotics is probably the greatest example of how drugs have been discovered through side effects. 

This bona fide antipsychotic property of chlorpromazine was established especially by two German studies, which looked at the dose dependence of the effect. Clinical use of this antipsychotic property of chlorpromazine spread between 1953 and 1955 through Europe to America via Canada where it was marketed by Smith Kline under the trade name Thorazine. Laborit can therefore claim to be the father of psychopharmacology, now a massive endeavor and industry, built upon the foundation of a poor antihistamine  

At this time, there was no knowledge of the molecular basis of chlor-promazine s effect or the molecular target. Knowledge of the molecular basis came 20 years later in 1972 when Paul Greengard s laboratory established the cormection with the dopamine receptor Dj. This led the whole industry to look for a new antipsychotic better than chlorpromazine and to new agents tested directly in multiple clinical trials. Further research 20 years later showed that much of the antipsychotic effect was through another variant of the dopamine receptor, the D2 receptor, not the originally 

Accounts vaiy in detail and in assigning credit. Some accounts credit the first use on a psychiatric patient to Hamon, Paraire, Velluz. Further testing as an antipsychotic is credited to Delay, Denikes and Harl in a mental hospital setting. 

The good fortune of finding chlorpromazine accelerated the development of new treatments. Without it, the link between the dopaminergic system and antipsychotic activity would, however, have been found by other careful observation. 

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