![]() ![]() 1993) stimulation of 5HT 1A receptors ( Sharma and Shapiro 1996, for review Newman-Tancredi et al. These properties include a high ratio of 5HT 2A to D 2 receptor affinities ( Meltzer, 1995, for review Meltzer et al. ![]() The pharmacological properties of ziprasidone may be predictive of enhanced clinical efficacy and a favorable tolerability profile, as compared with other agents, in the treatment of schizophrenia ( Seeger et al. Ziprasidone also exhibited selectivity for prefrontal cortical vs. The inhibition by ziprasidone of the firing of dorsal raphe 5HT neurons was antagonized by the selective 5HT 1A antagonist WAY-100,635, as was the elevation of extracellular levels of dopamine in the medial frontal cortex, establishing in vivo 5HT 1A agonist activity ( Reynolds et al. After systemic administration, ziprasidone produced relatively modest increases in dopamine metabolites as compared with haloperidol ( Seeger et al. In vitro functional dopamine receptor antagonism by ziprasidone has been demonstrated by concentration-dependent blockade of effects induced by a D 2 agonist, quinpirole (inhibition of forskolin-stimulated adenylate cyclase) ( Seeger et al. The results indicate that ziprasidone is effective and well tolerated in the treatment of the positive, negative, and depressive symptoms of an acute exacerbation of schizophrenia or schizoaffective disorder. ![]() Ziprasidone was shown to have a very low liability for inducing movement disorders and weight gain. The most frequent adverse events associated with ziprasidone were generally mild dyspepsia, nausea, dizziness, and transient somnolence. The percentage of patients experiencing adverse events was similar in each treatment group, and resultant discontinuation was rare. Ziprasidone 160 mg/day significantly improved depressive symptoms in patients with clinically significant depression at baseline (MADRS ≥ 14, over-all mean 23.5) ( p <. Both doses of ziprasidone were statistically significantly more effective than placebo in improving the PANSS total, BPRS total, BPRS core items, CGI-S, and PANSS negative subscale scores ( p <. In this double-blind study, patients with an acute exacerbation of schizophrenia or schizoaffective disorder were randomized to receive either ziprasidone 80 mg/day (n = 106) or 160 mg/day (n = 104) or placebo (n = 92), for 6 weeks. ![]()
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