Anticonvulsant agents primidone

The anticonvulsant agent primidone (4.246) is the 2-dihydro derivative of phenobarbital (4.247), which is one of its metabolites. The second major metabolite, 2-ethyl-2-phenylmalondiamide (4.248), is produced by a double C-N cleavage [160]. The profile of plasma levels in rats strongly suggests that 2-ethyl-2-phenylmalondiamide is not derived from the metabolite phenobarbital, but directly from primidone. Indeed, a C(2)-hydroxylated metabolite serves as an intermediate for both detected metabolites (see also Chapt. 6 in [21]). N-Alkyl derivatives of primidone yield a greater proportion of ring-opened metabolites, an observation explained by their higher susceptibility to oxidative metabolism at C(2) [161]. 

Gerson, B. Bell, F. Chan, S. Antiepileptic agents—primidone, phenobarbital, phenytoin, and carbamazepine by reversed-phase liquid chromatography. Clin.Chem., 1984, 30, 105-108 Kapetanovic, I.M. Kupferberg, H.J. Nafimidone, an imidazole anticonvulsant, and its metabolite eis potent inhibitors of microsomal metabolism of phenytoin and carbamazepine. Drug Metab.Dispos., 1984, 12, 560-564 [microsomal incubations rat liver column temp 50 extracted metabolites 2-methylcarbamazepine (IS)]... 

Primidone [125-33-7] -as antiepileptic agent [HYPNOTICS, SEDATIVES, ANTICONVULSANTS, AND ANXIOLYTICS] (Vol 13)... 

True hypersensitivity reactions to phenytoin are related to the "aromatic" anticonvulsants. Thus, in patients in whom a reaction is suspected, other arene anticonvulsants such as carbamazepine, oxcarbazepine, phenobarbital, or primidone should be avoided, as there is a high rate of cross-reactivity (estimated as high as 80%). Valproic acid is an agent that can be safely used as an alternative anticonvulsant in such patients. 

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