Chemical Properties
White Solid
Uses
Labelled Rufinamide (R701552). Antiepileptic triazole derivative which decreases firing by neurons at sodium channels. Anticonvulsant.
Uses
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
Biological Activity
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.
Definition
ChEBI: Rufinamide is a heteroarene and an aromatic amide.
General Description
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.
Biochem/physiol Actions
Broad-spectrum anticonvulsant.
Clinical Use
Adjunctive treatment of seizures in Lennox-Gastaut
syndrome
Side effects
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.
Synthesis
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.
Drug interactions
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.
Metabolism
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.
storage
room temperature (desiccate)
References
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
