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  • Title: The psychopharmacology of ziprasidone: receptor-binding properties and real-world psychiatric practice.
    Author: Stahl SM, Shayegan DK.
    Journal: J Clin Psychiatry; 2003; 64 Suppl 19():6-12. PubMed ID: 14728084.
    Abstract:
    Schizophrenia is a highly complex disorder characterized by a diversity of symptoms, psychotic and nonpsychotic, that most likely arise from heterogeneous neuroanatomical and neurochemical malfunctions. As with all antipsychotic agents, ziprasidone targets the key hypothetical neurochemical disturbance in psychosis-excessive dopamine neurotransmission at dopamine D2 receptors in the mesolimbic pathway of the brain-presumably responsible for the positive symptoms of schizophrenia. Like other atypical antipsychotic agents, ziprasidone is a serotonin-2A (5-HT2A)/dopamine D2 antagonist; however, its in vitro 5-HT2A/D2 receptor affinity ratio is higher than that of the other first-line atypical antipsychotic agents (namely, risperidone, olanzapine, quetiapine, and aripiprazole). Ziprasidone also exhibits potent interaction with 5-HT2C, 5-HT1D, and 5-HT1A receptors in human brain tissue, characteristics that predict heightened negative symptom relief, enhanced modulation of mood, cognitive improvement, and reduced motor dysfunction. Ziprasidone has moderate affinity for serotonin and norepinephrine reuptake sites, predicting antidepressant/anxiolytic activity. On the other hand, ziprasidone's low affinity for alpha1-adrenoceptors, as well as histamine H1 and muscarinic M1 receptors, suggests that patients should experience relatively little orthostatic hypotension, sedation, cognitive disturbance, weight gain, or dysregulation of prolactin levels. Efficacy and tolerability data from trials to date indicate that ziprasidone's clinical activity is consistent with its receptor profile.
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