JF-NP-26 是 Raseglurant 的无活性光笼衍生物，也是第一个光笼mGlu5受体负性变构调节剂。在可见光波段 (405 nm) 用光脉冲激发 JF-NP-26。JF-NP-26 诱导自由行为动物炎症性和神经病理性疼痛模型的光依赖性缓解疼痛作用。
| 生物活性 | JF-NP-26, an inactive photocaged derivative of raseglurant, is the first cagedmGlu5 receptornegative allosteric modulator. Uncaging of JF-NP-26 is elicited withlightpulses in the visible spectrum (405 nm). JF-NP-26 induces light-dependent analgesia in models of inflammatory and neuropathic pain in freely behavinganimals[1]. |
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体外研究
(In Vitro) | The authors assessed the JF-NP-26-mediated negative allosteric modulation of mGlu5 receptor-induced responses to the orthosteric agonist quisqualate, by using an inositol phosphate (IP) accumulation assay. while JF-NP-26 didn’t show activity in dark conditions, its negative allosteric modulator (NAM) activity is rescued upon 405 nm visible light illumination (pIC50=7.1)[1].
Agonist challenge induced a robust mGlu5 receptor-mediated intracellular calcium rise both in dark and under 405 nm illumination, which was blocked by raseglurant. JF-NP-26 is unable to restrain agonist-mediated signalling in dark conditions, it abolished mGlu5 receptor-mediated intracellular calcium accumulation upon 405 nm irradiation, thus demonstrating a light-dependent negative allosteric modulator activity[1].
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体内研究
(In Vivo) | JF-NP-26 (10 mg/kg; i.p.; irradiated at 405 nm (or dark) for 5 min) significantly increased pain thresholds in CCI mice only after thalamic irradiation[1].
JF-NP-26 (10 mg/kg; i.p.; at 405 nm light (or dark) for 5 min) shows light-dependent analgesic efficacy in neuropathic pain[1].
Systemic administration and in vivo photoactivation of JF-NP-26 does not impair memory in mouse[1].
| Animal Model: | Adult male C57BL/6J mice weighing 20-25 g (chronic constriction injury (CCI) model)[1] | | Dosage: | 10 mg/kg | | Administration: | I.p.; irradiated at 405 nm (or dark) for 5 min | | Result: | Significantly increased pain thresholds in CCI mice only after thalamic irradiation. |
| Animal Model: | Formalin animal model of pain adult male CD-1 mice[1] | | Dosage: | 10 mg/kg | | Administration: | I.p.; at 405 nm light (or dark) for 5 min | | Result: | Unable to promote antinociception in dark conditions, it elicited antinociception following direct hind paw irradiation both at phase I (5 min after formalin injection in the hind paw) and phase II (20–30 min after formalin injection). |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | Please store the product under the recommended conditions in the Certificate of Analysis. |
