Disease relevance of Sarizotan

• In contrast, the same dose of sarizotan reduced levodopa-induced choreiform dyskinesias by 91 +/- 5.9% [1].
• In the bar catalepsy test, when administered alone, haloperidol, olanzapine and risperidone produced marked catalepsy, whereas, at doses up to 40 mg/kg, aripiprazole, SLV313, SSR181507, and sarizotan produced little or no catalepsy [2].
• Sarizotan effectively suppresses levodopa-induced dyskinesia in primate and rodent models of Parkinson's disease, and tardive dyskinesia in a rodent model [3].

Psychiatry related information on Sarizotan

• CONCLUSIONS: While REM sleep was suppressed, the endocrine effects of 20 mg sarizotan at night were weak [4].

High impact information on Sarizotan

• METHODS: The 5-HT1A receptor agonist sarizotan (EMD128130) was systemically administered alone and together with levodopa to parkinsonian rats and nonhuman primates [1].
• When 5-HT1A receptors were blocked by pretreatment with WAY100635 (2.5 mg/kg, s.c.), cataleptogenic properties of SSR181507 and sarizotan were unmasked, and the catalepsy induced by bifeprunox was enhanced [2].
• Results from clinical trials suggest that sarizotan significantly alleviates levodopa-induced dyskinesia [3].
• Here we report the functional effects of sarizotan on human D2-like dopamine receptors (D2S, D2L, D3, D4.2 and D4.4) individually expressed in the AtT-20 neuroendocrine cell line [3].
• RESULTS: After administration of sarizotan, a significant reduction of REM sleep and total sleep time in conventional sleep EEG and a significant reduction of sigma- and theta-power in spectral analysis were observed [4].

Chemical compound and disease context of Sarizotan

• Whereas ziprasidone and aripiprazole did not markedly reduce the effects of haloperidol, SLV313 and sarizotan attenuated CLP catalepsy [5].
• 5-Hydroxytryptamine 1a (5-HT(1a)) receptor agonists, such as sarizotan and tandospirone, are reported to reduce levodopa-induced dyskinesia in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated macaques and in Parkinson's disease without worsening motor disability [6].

Biological context of Sarizotan

• CONCLUSIONS: At a dose higher than that intended for clinical use (1 mg b.i.d.), sarizotan had no effect on the metabolism and pharmacokinetics of specific probe drugs for CYP isoenzymes 1A2, 2C19, 2C9, 2D6 and 3A4 [7].

Anatomical context of Sarizotan

• In medial prefrontal cortex, dopamine levels were increased by SSR181507, SLV313, sarizotan, and (+)8-OH-DPAT [8].
• These findings suggest that the anti-dyskinetic properties of sarizotan could be mediated via its 5-HT(1A) agonist actions in the motor cortex, leading to reduced activity in the corticostriatal glutamate pathways with reduced activation of the striatopallidal GABA pathway mediating motor inhibition [9].
• However, sarizotan at higher doses decreased DA precursor accumulation in reserpinized rats and induced contralateral rotational behavior in unilaterally substantia nigra lesioned rats, indicating some intrinsic dopaminergic activity; at D2 receptors sarizotan may act as a partial agonist, depending on the dopaminergic impulse flow [10].

Associations of Sarizotan with other chemical compounds

• The effects of sarizotan, a 5-HT(1A) agonist with additional affinity for D(3) and D(4) receptors, have been studied on the corticostriatal glutamate pathways using dual-probe microdialysis in the awake rat [9].

Gene context of Sarizotan

• We investigated the effect of sarizotan on the clinical pharmacokinetics of probe drugs for cytochrome P450 (CYP) to evaluate the risk of CYP-related drug-drug interactions [7].
• To evaluate this hypothesis, effects of a selective 5-HT1A agonist, sarizotan, given orally at 2 and 5 mg twice daily to 18 relatively advanced parkinsonian patients, were compared with baseline placebo function during a 3-week, double-blind, placebo-controlled, proof-of-concept study [11].

References