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| 融点 | 232-234?C | | 沸点 | 473.8±55.0 °C(Predicted) | | 比重(密度) | 1.52±0.1 g/cm3(Predicted) | | 闪点 | 2℃ | | 貯蔵温度 | -20°C | | 溶解性 | DMSO: soluble9mg/mL | | 酸解離定数(Pka) | 14.37±0.50(Predicted) | | 外見 | powder | | 色 | white | | Merck | 14,8293 | | 安定性： | Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 1 month. |
| | ルフィナミド Usage And Synthesis |
| 外観 | 白色～ほとんど白色粉末～結晶 | | 効能 | 抗てんかん薬 | | 商品名 | イノベロン (エーザイ) | | 説明 | Approximately 2.5 million people worldwide are afflicted with epilepsy, a
devastating neurological disorder diagnosed by the tendency toward recurrent,
unprovoked seizures, often of unknown etiology. Rufinamide has been launched primarily as adjunctive
therapy of LGS. Its proposed mechanism of action involves the limitation of
firing of sodium-dependent action potentials. The ultimate result is membrane
stabilization. Since it does not exhibit measurable binding to monoamine,
acetylcholine, histamine, glycine, AMPA/kainate, NMDA, or GABA receptors or
systems, these receptor-mediated pathways are not anticipated to be involved in
the exertion of rufinamide’s effects. Rufinamide displayed efficacy in several
electrical and chemical animal seizure models. | | 説明 | Lennox-Gastaut syndrome (LGS) is a severe pediatric epilepsy syndrome characterized by multiple seizure types. Rufinamide is an anticonvulsant. It inhibits the activation of voltage-gated sodium channel 1.1 (Nav1.1) when used at a concentration of 100 μM. Rufinamide inhibits Nav1.1, but not Nav1.2, Nav1.3, and Nav1.6, opening and increases the action potential threshold in primary rat hippocampal neurons. It is an inhibitor of carbonic anhydrase VA (CAVA; Ki = 343.8 nM) that is selective for CAVA over CAI and CAII (Kis = >10,000 nM for both). Rufinamide (100 μM) prolongs the preictal phase and reduces seizure-like event frequency in an in vitro model of epileptiform activity in rat hippocampal slices. It inhibits seizures induced by pentylenetetrazole in a mouse model of epilepsy (ED50 = 54 mg/kg, i.p.) and reduces kainic acid-induced neuronal cell death in the mouse hippocampal CA3 region when used at doses of 25, 50, and 100 mg/kg. Formulations containing rufinamide have been used in the treatment of seizures associated with Lennox-Gastaut Syndrome (LGS). | | 化学的特性 | White Solid | | Originator | Novartis (US) | | 使用 | Rufinamide, a triazole derivative, is an anticonvulsant medication. It is used in combination with other medication and therapy to treat Lennox–Gastaut syndrome and various other seizure disorders. Rufinamide is presumed to involve stabilization of the so | | 使用 | Labelled Rufinamide (R701552). Antiepileptic triazole derivative which decreases firing by neurons at sodium channels. Anticonvulsant. | | 使用 | Rufinamide has been used to test its analgesic effect on neuropathic pain in spared nerve injury (SNI) model. | | 定義 | ChEBI: Rufinamide is a heteroarene and an aromatic amide. | | brand name | Inovelon | | 一般的な説明 | An antiepileptic drug and anticonvulsant, Rufinamide is approved for the treatment of partial seizures associated with Lennox-Gastaut syndrome in adults and children 4 years and older. Rufinamide is marketed as Banzel® in the US and Inovelon® in the EU. | | 生物活性 | Board spectrum anticonvulsant. Prolongs the inactivation of sodium channels and limits the frequency of action potential firing in cultured and acutely isolated neurons. Displays anticonvulsive activity in a range of animal seizure models. | | Biochem/physiol Actions | Broad-spectrum anticonvulsant. | | 臨床応用 | Adjunctive treatment of seizures in Lennox-Gastaut
syndrome | | 副作用 | Rufinamide was well tolerated with the most common adverse events including fatigue, somnolence, tremors, mild-to-moderate dizziness, nausea, headache, and diplopia. Since rufinamide is not metabolized by the CYP450 system, it is anticipated to have a low potential for interaction with drugs metabolized by the CYP isozymes. Rufinamide, however, does exhibit clinically relevant interactions with other antiepileptic drugs; concomitant treatment with valproate results in a reduction in rufinamide clearance while concomitant treatment with phenytoin, primidone, phenobarbital, carbamazepine, or vigabatrin causes an increase in rufinamide clearance. In these situations, rufinamide dosage adjustment may be required. | | 合成 | While rufinamide may be prepared by several related routes, the preferred starting material is 2,6-difluorobenzyl azide. Reaction with either 2-propynoic acid or 2-chloroacrylonitrile affords 1-(2,6-difluorobenzyl)-1H-1,2,3-triazole-4-carboxylic acid or 1-(2,6-difluorobenzyl)- 1H-1,2,3-triazole-4-carbonitrile, respectively. For the carboxylic acid Shridhar Hegde and Michelle Schmidt intermediate, treatment with thionyl chloride followed by concentrated aqueous ammonium hydroxide or conversion to its methyl ester (methanol/sulfuric acid) with subsequent ammonolyis provides rufinamide. | | 薬物相互作用 | Potentially hazardous interactions with other drugs
Antidepressants: antagonism of anticonvulsant effect
(convulsive threshold lowered); avoid with St John’s
wort.
Antimalarials: mefloquine antagonises
anticonvulsant effect.
Antipsychotics: antagonism of anticonvulsant effect
(convulsive threshold lowered).
Oestrogens and progestogens: metabolism
accelerated by rufinamide - reduced contraceptive
effect.
Orlistat: possibly increased risk of convulsions with
orlistat.
Ulipristal: possibly reduces contraceptive effect. | | 代謝 | Almost exclusively eliminated by metabolism
via hydrolysis of the carboxylamide group to the
pharmacologically inactive acid derivative CGP 47292.
Cytochrome P450-mediated metabolism is very minor.
The formation of small amounts of glutathione conjugates
cannot be completely excluded. 84.7% was excreted by the
renal route. | | 貯蔵 | room temperature (desiccate) | | 参考文献 | 1) Hakimian et al. (2007), Rufinamide: a new anti-epileptic medication; Expert Opin. Pharmacother. 8 1931
2) Gilchrist et al. (2014), Nav1.1 Modulation by a Novel Triazole Compound Attenuates Epileptic Seizures in Rodents; ACS Chem. Biol. 9 1204
3) Chen et al. (2018), Rufinamide, an antiepileptic drug, improves cognition and increases neurogenesis in the aged gerbil hippocampal dentate gyrus via increasing expressions of IGF-1, IGF-1R and p-CREB; Chem. Biol. Interact. 286 71 |
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