Ziprasidone mesylate

Ziprasidone (CP-88059) mesylate is an orally active combined 5-HT and dopamine receptor antagonist[1]. Ziprasidone mesylate has affinities for Rat D2 (Ki=4.8 nM), 5-HT2A (Ki=0.42 nM) and 5-HT1A (Ki=3.4 nM)[1].

Signaling Pathways >> GPCR/G Protein >> Dopamine Receptor

Signaling Pathways >> Neuronal Signaling >> Dopamine Receptor

Research Areas >> Neurological Disease

Signaling Pathways >> GPCR/G Protein >> 5-HT Receptor

Signaling Pathways >> Neuronal Signaling >> 5-HT Receptor

Rat 5-HT2 Receptor:0.42 nM (Ki)

Rat 5-HT1A Receptor:3.4 nM (Ki)

Rat D2 Receptor:4.8 nM (Ki)

Ziprasidone mesylate (0-500 nM, 150 seconds) blocks wild-type hERG current[2]. Cell Viability Assay[2] Cell Line: HEK-293 cells Concentration: 0-500 nM Incubation Time: 150 seconds Result: Blocked wild-type hERG current in a voltage- and concentration-dependent manner (IC50 = 120 nm).

Ziprasidone mesylate (oral gavage; 20 mg/kg; once daily; 7 weeks) results in weight loss, low level physical activity, high resting energy expenditure and greater capacity for thermogenesis when subjected to cold[3]. Animal Model: Eight-week-old female Sprague-Dawley rats weighing 200 to 250 g[3] Dosage: 20 mg/kg Administration: Oral gavage; 20 mg/kg; once daily; 7 weeks Result: Gained significantly less weight (P = 0.031), had a lower level of physical activity (P = 0.016), showed a higher resting energy expenditure (P < 0.001), and displayed a greater capacity for thermogenesis when subjected to cold (P < 0.001).

[1]. H Rollema, et al. 5-HT(1A) receptor activation contributes to ziprasidone-induced dopamine release in the rat prefrontal cortex. Biol Psychiatry. 2000 Aug 1;48(3):229-37.

[2]. Zhi Su, et al. Block of hERG channel by ziprasidone: biophysical properties and molecular determinants. Biochem Pharmacol. 2006 Jan 12;71(3):278-86.

[3]. Subin Park, et al. The effect of ziprasidone on body weight and energy expenditure in female rats. Metabolism. 2012 Jun;61(6):787-93.