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Schizophrenia therapy: beyond atypical antipsychotics

Nature Reviews Drug Discovery volume 7, pages 471–472 (2008)Cite this article

The first generation of antipsychotics — termed conventional or 'typical' antipsychotics — such as haloperidol, inhibit dopamine D2 receptors and are moderately effective in treating positive symptoms of schizophrenia (for example, hallucinations), but may cause extrapyramidal movement disorders. Second-generation 'atypical' antipsychotics — such as Lilly's Zyprexa (olanzapine), Johnson & Johnson's Risperdal (risperidone) and AstraZeneca's Seroquel (quetiapine) — inhibit D2 receptors in conjunction with other receptors (notably 5-hydroxytryptamine 2A (5-HT2A) receptors) (Table 1). Atypical antipsychotics have proved less likely to cause movement disorders, but are associated with weight gain, prolactin and glucose elevation, and sedation.

Zyprexa is widely regarded as being the most effective atypical antipsychotic on the market, but in the past 3 years, issues related to side effects have led to the drug losing nearly half its market share, as well as over 28,000 lawsuits, again indicating the need for drugs with better side-effect profiles. Furthermore, with all of the currently marketed atypicals facing generic competition within 5 years, there is a considerable market opportunity for new branded antipsychotics.

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Figure 1: Worldwide sales of drugs for schizophrenia, 1993–2007.
Figure 2: Metabotropic glutamate receptors (mGluRs) in the synapse.

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Authors and Affiliations

  1. Eric M. Snyder and Melanie R. Murphy are at Mehta Partners Global BioPharmaceutical Investments, 276 Fifth Avenue Suite 1100, New York 10001, USA. snyder@mpglobal.com,

    Eric M. Snyder & Melanie R. Murphy

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  1. Eric M. Snyder
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  2. Melanie R. Murphy
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Mehta Partners Investments include Merck and Acadia.

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Snyder, E., Murphy, M. Schizophrenia therapy: beyond atypical antipsychotics. Nat Rev Drug Discov 7, 471–472 (2008). https://doi.org/10.1038/nrd2571

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