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Safinamide

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Chemical Structure| 133865-89-1 同义名 : FCE 26743;EMD 1195686;PNU-15774E
CAS号 : 133865-89-1
货号 : A189271
分子式 : C17H19FN2O2
纯度 : 98%
分子量 : 302.34
MDL号 : MFCD00897036
存储条件：

粉末 Keep in dark place,Inert atmosphere,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 105 mg/mL(347.29 mM)，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
靶点

  • MAO-B

    MAO-B, IC50:98 nM
描述 Glial cells contain two enzymes that metabolize biogenicamines: COMT and MAO. MAO, located in the outer mitochondrial membrane, occurs as two isozymes: A and B. MAO-A is predominantly found in the intestinal tract and, in the CNS, presynaptic neurons; MAO-B is mainly located in the brain, generally in glial cells near dopaminergic synapses. MAO-B regulates the free concentrations of biogenic amines in the synaptic cleft[3].Safinamide is a highly selective and reversible MAO-B inhibitor that produces an increase in extracellular levels of dopamine in the striatum[4]. The non-dopaminergic mechanism of action involves state- and use-dependent blockade of voltagegated sodium channels and modulation of N-type calcium channels, thereby inhibiting glutamate release[5]. In rats, safinamide was &5000-fold more potent in inhibiting MAO-B than MAO-A [6]. In humans, safinamide provided platelet MAO-B inhibition at doses of C0.5 mg/kg,but did not inhibit MAO-A enzyme activity at a dose of 10 mg/kg[7].Safinamide has demonstrated neuroprotective, neurorescuing, anti-inflammatory and tremorolytic properties in several animal models,and was shown to reduce the duration and intensity of levodopa-induced dyskinesia in parkinsonian monkeys[8]. in vitro , safinamide is not a substrate for the transporters P-glycoprotein, BCRP, OAT1B1, OAT1B3, OATP1A2 or OATP2B1. The metabolite safinamide acid is not a substrate for OCT2 or OAT1 but is a substrate for OAT3,although potential pharmacokinetic interactions are not likely to be clinically relevant. Safinamide acid does not inhibit OCT2, MATE1 or MATE2-K[9].
临床研究
NCT号 适应症或疾病 临床期 招募状态 预计完成时间 地点
NCT00627640 Idiopathic Parkinson's Disease Phase 3 Completed - -
NCT00642889 Parkinson's Disease Phase 3 Completed - -
NCT01028586 Idiopathic Parkinson's Disease Phase 3 Terminated(Trial is terminated... 展开 >> due to a company decision to return all rights for Safinamide back to Newron Pharmaceuticals) 收起 << - Switzerland ... 展开 >> Enquire Central Contact Geneva, Switzerland 收起 <<
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

3.31mL

0.66mL

0.33mL

16.54mL

3.31mL

1.65mL

33.08mL

6.62mL

3.31mL
参考文献

[1]Binda C, Wang J, et al. Structures of human monoamine oxidase B complexes with selective noncovalent inhibitors: safinamide and coumarin analogs. J Med Chem. 2007 Nov 15;50(23):5848-52.

[2]Caccia C, Maj R, et al. Safinamide: from molecular targets to a new anti-Parkinson drug. Neurology. 2006 Oct 10;67(7 Suppl 2):S18-23.

[3] Bartl J,et al. Chronic monoamine oxidase-B inhibitor treatment blocks monoamine oxidase-A enzyme activity. J Neural Transm. 2014;121:379–83.

[4] Safinamide for Parkinson's disease. Drug Ther Bull. 2018 May;56(5):54-57.

[5] European Medicines Agency. Safinamide: summary of product characteristics. 2014.

[6] Caccia C, Maj R, Calabresi M, et al. Safinamide: from molecular targets to a new anti-Parkinson drug. Neurology. 2006;67(7 Suppl2):S18–23.

[7] Cattaneo C, Caccia C, Marzo A, et al. Pressor response to intravenous tyramine in healthy subjects after safinamide, a novel neuroprotectant with selective, reversible monoamine oxidase B inhibition. Clin Neuropharmacol. 2003;26(4):213–7

[8] Gregoire L, Jourdain VA, Townsend M, et al. Safinamide reduces dyskinesias and prolongs l-dopa antiparkinsonian effect in parkinsonian monkeys. Parkinsonism Relat Disord. 2013;19(5):508–14.

[9]European Medicines Agency. Xadago assessment report. 2014.