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Int J Neurosci. 2004 Jun;114(6):593-611.

Are the cognitive effects of atypical antipsychotics influenced by their affinity to 5HT-2A receptors?

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School of Health and Social Sciences, University of Gloucestershire, Francis Close Hall Campus, Cheltenham, Gloucestershire, United Kingdom.


It is well documented that atypical antipsychotics have an influence on cognitive function in patients with schizophrenia, although the neurochemical basis for this effect is not well understood. One suggestion is that the effects are exerted through action on 5HT-2A receptors, which leads to changes in the level of dopamine in the prefrontal cortex. The following study explored this hypothesis by comparing the cognitive effects of the atypical antipsychotics which have a high affinity for 5HT-2A receptors, with those that have little or no affinity to these receptors. Forty-four patients with a DSM-IV diagnosis of schizophrenia were recruited within 6 weeks of starting one of the atypical antipsychotics: clozapine, olanzapine, risperidone, quetiapine, or amisulpride. The patients were divided into two groups according to the 5HT-2A affinity of the individual medications (high 5HT-2A affinity--clozapine, olanzapine, risperidone vs. low 5HT-2A affinity--quetiapine, amisulpride). Patients were tested on a broad range of neuropsychological measures after 9 months and 18 months of treatment. The high 5HT-2A affinity group showed a decrement in performance on tests of visual recognition memory and planning ability. In contrast, the low-5HT-2A affinity group showed improvements on these measures in addition to others. The 5HT-2A affinity of the atypical antipsychotics is an important determinant of their cognitive effects.

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