Disease relevance of NAFIMIDONE

• This study has demonstrated that although nafimidone can modify both threshold and suprathreshold elicited kindled amygdaloid seizures, it lacks significant specificity in this model of epilepsy [1].
• Nafimidone (25-50 mg/kg) significantly reduced supranthreshold elicited afterdischarge length and seizure severity only at doses with some prestimulation toxicity [1].

Psychiatry related information on NAFIMIDONE

• This agent was twice as potent as nafimidone in inhibiting maximal electroshock seizures in mice (po ED50's = 25 and 56 mg/kg, respectively) and considerably less toxic in the rat (po LD50's = 4550 and 504 mg/kg, respectively) [2].

High impact information on NAFIMIDONE

• Pharmacokinetics of nafimidone in patients with chronic intractable epilepsy [3].
• Structure-activity relationships of (arylalkyl)imidazole anticonvulsants: comparison of the (fluorenylalkyl)imidazoles with nafimidone and denzimol [2].
• These data suggest induction of a predominating cytochrome P-448-type of Phase I drug-metabolizing activity by nafimidone alcohol [4].
• However, the AUC of nafimidone alcohol was 30% higher after oral administration of nafimidone than that after iv administration of nafimidone [5].
• Chronic administration of nafimidone alcohol caused induction of hepatic drug metabolism typified by shortening of pentobarbital sleeping time in vivo in male mice and a doubling of hepatic microsomal cytochrome P-450 content in male rats [4].

Biological context of NAFIMIDONE

• Thus, nafimidone and its metabolite were shown to be potent inhibitors of major biotransformation pathways of two important antiepileptic drugs [6].
• Systemic clearance of nafimidone from plasma after iv administration was approximately 2 times higher than hepatic blood flow in rats, and the oral bioavailability was 15% [5].
• The IC50 values for CBZ epoxidation were 4.46 x 10(-7) and 2.95 x 10(-7) M, respectively, in the presence of denzimol and nafimidone [7].

Anatomical context of NAFIMIDONE

• Nafimidone alcohol produced a type II difference spectrum when added to rat hepatic microsomes [4].
• Distribution of nafimidone-related radioactivity was widespread with highest concentrations associated with liver, kidney, adrenals, and the gastrointestinal tract [5].

Associations of NAFIMIDONE with other chemical compounds

• Development of a stability-indicating assay for nafimidone [1-(2-naphthoylmethyl)imidazole hydrochloride] by high-performance liquid chromatography [8].
• 1. The biotransformation of nafimidone, an imidazole-substituted anticonvulsant, has been studied by characterization of urinary metabolites in dogs, cynomolgus monkeys, baboons and man [9].

Analytical, diagnostic and therapeutic context of NAFIMIDONE

• Simultaneous determination of nafimidone [1-(2-naphthoylmethyl)imidazole], a new anticonvulsant agent, and a major metabolite in plasma by high-performance liquid chromatography [10].
• After both iv and oral administration, nafimidone was rapidly eliminated from plasma (t 1/2 about 5 min), with concomitant formation of a pharmacologically active, nonconjugated metabolite, nafimidone alcohol [5].

References