Mirogabalin

产品说明书

Print
Chemical Structure| 1138245-13-2 同义名 : DS5565
CAS号 : 1138245-13-2
货号 : A181027
分子式 : C12H19NO2
纯度 : 99%+
分子量 : 209.285
MDL号 : MFCD28411425
存储条件：

Pure form Sealed in dry,2-8°C

In solvent -20°C:3-6个月-80°C:12个月
溶解度 :

H2O: 7.5 mg/mL(35.84 mM)，配合低频超声助溶
动物实验配方：
生物活性
描述 Mirogabalin, a novel ligand for the α2δ subunit of voltage-gated calcium channels, is being developed to treat pain associated with diabetic peripheral neuropathy and postherpetic neuralgia. Mirogabalin shows potent and selective binding affinities for the human and rat α2δ subunits, and slower dissociation rates for the α2δ-1 subunit than the α2δ-2 subunit. It shows potent and long-lasting analgesic effects in rat models of neuropathic pain, and wider safety margins for side effects of the central nervous system[3]. In rats subjected to spinal cord injury, mechanical allodynia was demonstrated by a decreased paw withdrawal threshold. A single oral administration of mirogabalin (2.5, 5, or 10 mg/kg) significantly increased the paw withdrawal threshold. The effects of mirogabalin were still significant 6 or 8 h after administration. The paw withdrawal threshold AUC was significantly higher in the treated animals than in the control group[4]. Mirogabalin relieved DPNP (diabetic peripheral neuropathic pain) in a dose-dependent manner; mirogabalin 30 mg/day showed statistically significant pain relief (vs placebo) in Asian DPNP patients. All doses of mirogabalin tested were well tolerated[5]. The most frequent treatment-emergent adverse events (TEAEs)-dizziness and somnolence-were expected based on mirogabalin's mechanism of action. After oral administration, mirogabalin was rapidly absorbed (time to maximum concentration, ∼1 hour) and eliminated through urine unchanged (61%-72% urinary excretion)[6].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

4.78mL

0.96mL

0.48mL

23.89mL

4.78mL

2.39mL

47.78mL

9.56mL

4.78mL
参考文献

[1]Hutmacher MM, Frame B, et al. Exposure-response modeling of average daily pain score, and dizziness and somnolence, for mirogabalin (DS-5565) in patients with diabetic peripheral neuropathic pain. J Clin Pharmacol. 2016 Jan;56(1):67-77.

[2]Vinik A, Rosenstock J, et al; DS5565-A-U201 US Phase II Study Investigators. Efficacy and safety of mirogabalin (DS-5565) for the treatment of diabetic peripheral neuropathic pain: a randomized, double-blind, placebo- and active comparator-controlled, adaptive proof-of-concept phase 2 study. Diabetes Care. 2014 Dec;37(12):3253-61.

[3]Domon Y, Arakawa N, Inoue T, et al. Binding Characteristics and Analgesic Effects of Mirogabalin, a Novel Ligand for the α2δ Subunit of Voltage-Gated Calcium Channels. J Pharmacol Exp Ther. 2018;365(3):573‐582

[4]Domon Y, Kitano Y, Makino M. Analgesic effects of the novel α₂δ ligand mirogabalin in a rat model of spinal cord injury. Pharmazie. 2018;73(11):659‐661

[5]Baba M, Matsui N, Kuroha M, Wasaki Y, Ohwada S. Mirogabalin for the treatment of diabetic peripheral neuropathic pain: A randomized, double-blind, placebo-controlled phase III study in Asian patients. J Diabetes Investig. 2019;10(5):1299‐1306

[6]Brown K, Mendell J, Ohwada S, et al. Tolerability, pharmacokinetics, and pharmacodynamics of mirogabalin in healthy subjects: Results from phase 1 studies. Pharmacol Res Perspect. 2018;6(5):e00418.