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Similarities between amphetamine toxicity and schizophrenia led Paul Janssen to study amphetamine blockers.

In the late 1950s, one such compound, haloperidol, became a major treatment for schizophrenia.

In the 1960s, biochemical theories of depression led to the design of molecules resulting in fluoxetine.

There are, then, many different pathways to new drugs, including intuition and theory-guided molecule design.

There have been many different pathways to developing psychotropic drugs. None, perhaps, have differed as much as the discovery of haloperidol, which exemplifies the role of creative intuition, and the development of fluoxetine, which came from systematic development of a molecule based on a theory of chemistry underlying mental illness. Let's look at each of these, and see what they say about the genesis of new medicines.

The story of haloperidol began with an observation about the use of performance-enhancing drugs by professional cyclists. Amphetamines were often taken by cyclists in the postwar years, and around 1955, the Belgian physician and pharmacologist Paul Janssen (1926-2003) was told by his colleague Fries Claes that the toxic symptoms they often displayed—including auditory hallucinations, delusions of persecution, thought disorders and stereotyped behaviors—resembled the clinical picture of paranoid schizophrenia. It was not an entirely new observation, having appeared as early as 1938. Indeed, in the early 1950s, several patients appeared in emergency departments of London hospitals with such symptoms, which cleared after admission, and were recognized as coming from what the medical student P.H. Connell named ‘amphetamine psychosis’ in 1953.

While Connell’s interest had been in alerting clinicians, Janssen gave these observations a new........

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