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Discovering risperidone: the LSD model of psychopathology

Abstract

In the 1970s and 1980s, Janssen Pharmaceutica Research, which had a broad interest in central nervous system disorders and nurtured intellectual freedom, developed original, and at times heretical, concepts. It took decades for the scientific community to endorse some of these concepts. Among them were such notions as an elementary particle of behaviour, the introduction of response quality in receptor theory, and the idea that tolerance does not develop to opioids. These concepts enabled the discovery of the antipsychotic risperidone, a unique full antagonist of the interoceptive effects of LSD.

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Figure 1: Structural formula of the pure LSD antagonists pirenperone and risperidone.
Figure 2: The risperidone drug-discovery process.

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Acknowledgements

The author is grateful to Drs M. Kleven, P. Pauwels and A. Newman-Tancredi for their contribution on an earlier version of this paper.

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FURTHER INFORMATION

Encyclopedia of Life Sciences

Opiates

Janssen Pharmaceutica

LocusLink

5-HT1A receptor

5-HT2A receptor

dopamine D2 receptor

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Colpaert, F. Discovering risperidone: the LSD model of psychopathology. Nat Rev Drug Discov 2, 315–320 (2003). https://doi.org/10.1038/nrd1062

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