Rufinamide anticonvulsant

Rufinamide is a structurally novel antiepUeptic agent that acts by reducing the frequency of liring of sodium-dependent neuronal action potentials. This drug is in Phase III clinical trials as a broad-spectrum anticonvulsant. 

Figure 6.11. Suggested pharmacophore model for anticonvulsants acting at the voltage-dependent sodium channel on the basis of molecular dynamics simulations on phenytoin (1), carbamazepine (2), lamotrigine (11), zonisamide (13), and rufinamide (60). Rema-oemide (58)is discussed in the text. (AfterRef 281.)...

Several authors have provided insight into the putative MBS receptor based on their structure-activity data. As noted by Unverferth et al. (281), there have been several attempts to postulate a general pharmacophore for the different anticonvulsant classes, all of which are anti-MES in animal studies and are, or have the potential to be, effective in generalized tonic-clonic seizures. These include benzodiazepines (282) barbiturates (283) triazolines (284) semicarbazones (248-261) and enami-nones (286-288), respectively and for different compounds with similar anticonvulsant profiles (289-292). The Unverferth model (Fig. 6.11) provides an excellent representation of the current anticonvulsants phenytoin (1), carbamazepine (2), lamotrigine (11), zonisamide (13), and rufinamide (60). Remace-mide (58) is also included as a possible candidate (Fig. 6.12). 

Figure 6.12. Selected anticonvulsants for the development of a pharmacophore model. The essential structural elements are indicated by dotted rectangles. 1 = phenytoin 2 = carbamazepine 11 = lamotrigine 13 = zonisamide 60 = rufinamide inset, 58 = remacemide. R, hydrophobic unit D, electron-donor group HAD, hydrogen donor/acceptor unit. (AfterRef 281.)...

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