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Chapter 32. Risperidone and Paliperidone

Donald C. Goff, M.D.
DOI: 10.1176/appi.books.9781585623860.418938

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Excerpt

A decade before clozapine was approved for marketing in the United States, Janssen Pharmaceuticals established a program to examine the potential role of serotonergic agents in schizophrenia. Early interest in serotonergic agents stemmed from a preclinical literature demonstrating that both behavioral effects of dopamine agonists and haloperidol-induced catalepsy could be modulated by serotonin2 (5-HT2) antagonists; in addition, the early butyrophenone derivative pipamperone, which was observed to reduce agitation and improve social activity in patients with severe depression, was found to possess primarily 5-HT2 antagonist activity (Ansoms et al. 1977; Leysen et al. 1978).

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FIGURE 32–1. Chemical structure of risperidone.
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TABLE 32–1. Receptor-binding affinities (Ki values, in nM) of risperidone (versus haloperidol and clozapine) in rat
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TABLE 32–2. Effect sizes on Positive and Negative Syndrome Scale (PANSS) symptom dimensions: North American trials (N = 513)
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TABLE 32–3. Side effects reported by patients with schizophrenia receiving placebo, risperidone, or haloperidol in the U.S. multicenter trial

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The pharmacokinetic profiles of risperidone and 9-hydroxyrisperidone (paliperidone) differ in which of the following ways?
2.
Risperidone’s serotonin 2A (5-HT2A) antagonist properties, combined with its dopamine 2 (D2) blockade, may produce which of the following positive effects?
3.
Risperidone is approved by the U.S. Food and Drug Administration (FDA) to treat all of the following disorders except
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