Posted by Netch on October 9, 2007, at 19:11:04
In reply to Inovelon, posted by Quintal on October 9, 2007, at 16:38:23
"Rufinamide [1-(2,6-difluorophenyl)methyl-1H-1,2,3-triazole-4-carboxamide; E 2080, CGP 33101, RUF 331] is triazole (3 nitrogens in a 5-membered ring) compound that bears some structural similarity with lamotrigine, a triazine (3 nitrogens in a 6-membered ring). Rufinamide is effective in the mouse MES test (ED50, 15.5 mg/kg, i.p.) and at higher doses is the PTZ test (54 mg/kg) (Schmutz et al., 1993; White et al., 2005). It is ineffective against absence-like seizures in WAG/Rij rats. The drug has a very low propensity for toxicity in the rotorod test (TD50, >500 mg/kg, i.p.). Overall, rufinamide has a distinctive profile in animal testing—activity in both MES and PTZ models and a very high protective index—that differentiates it from marketed AEDs. The efficacy of rufinamide in the MES test is compatible with sodium-channel blocking activity. In fact, the drug has been reported to prolong the inactivation of sodium channels and to limit the frequency of action potential firing in cultured and acutely isolated neurons (Karolchyk and Schmidt, 2002; McLean et al., 2005). In other studies, there were no effects on sodium channels at the concentrations tested (Vickery et al., 2004). In view of its unique profile, it seems unlikely that effects on sodium channels entirely explain the anticonvulsant activity of rufinamide. To date, no alternative mechanisms have emerged: there is no evidence for interactions with GABA or glutamate systems."
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1562526
"protective index of rufinamide, as shown in rodent models of epilepsy, is much higher than that of most common AEDs. Features which make it a desirable AED are: (i) a broad spectrum of anti-epileptic actions including both partial and symptomatic generalised epilepsy; (ii) a statistically significant reduction in seizure frequency in clinical trials; (iii) efficacy and safety shown in a broad range of age groups including children and the elderly; (iv) rapid oral absorption enabling quick titration to effective dose and (v) a benign adverse event profile. Most of the events did not lead to discontinuation in clinical trials. These features offer considerable advantages over the existing anti-epileptic drugs."http://www.ingentaconnect.com/content/apl/eid/2000/00000009/00000004/art00014
poster:Netch
thread:788111
URL: http://www.dr-bob.org/babble/20071009/msgs/788126.html