Blockade of drug-induced deficits in prepulse inhibition of acoustic startle by ziprasidone.

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Mansbach RS, Carver J, Zorn SH

Blockade of drug-induced deficits in prepulse inhibition of acoustic startle by ziprasidone.

Pharmacol Biochem Behav. 2001 Jul-Aug;69(3-4):535-42.

PubMed ID

11509214 [ View in PubMed

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Abstract

Ziprasidone, an antipsychotic with efficacy against core symptoms of schizophrenia and schizoaffective disorder, has a low incidence of extrapyramidal syndrome (EPS). Because of its high 5-HT(2A)/D(2) binding-affinity ratio and low EPS liability, ziprasidone is considered to belong to the newer class of "novel" antipsychotics typified by clozapine. Its unique pharmacological profile, however, distinguishes it from other novel agents. We evaluated ziprasidone in the prepulse inhibition (PPI) model, which is sensitive to clinically active antipsychotics. Male Wistar rats were tested in acoustic startle sessions in which some startle-eliciting stimuli were presented alone, and others were preceded by a weak prepulse. Administration of the dopamine agonist apomorphine (1 mg/kg) or the N-methyl-D-aspartate (NMDA) antagonist ketamine (10 mg/kg) significantly disrupted PPI. When coadministered with either of these compounds, clozapine (1-5.6 mg/kg sc) and ziprasidone (5.6-17.8 mg/kg po) significantly attenuated the declines in PPI. Haloperidol (0.03-0.56 mg/kg) also attenuated drug-induced deficits in PPI but to a lesser extent (and at higher doses) with ketamine than with apomorphine. Together, these data confirm that ziprasidone shares common effects in PPI models with other novel antipsychotics. Ziprasidone's affinity for non-D(2) receptors in the central nervous system may partly account for its attenuation of ketamine's effect.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Ziprasidone	5-hydroxytryptamine receptor 2A	Protein	Humans	Yes	Antagonist	Details