Disease relevance of NORFENFLURAMINE

• We propose that preferential stimulation of valvular 5-HT(2B) receptors by norfenfluramine, ergot drugs, or 5-HT released from carcinoid tumors (with or without accompanying 5-HT(2A) receptor activation) may contribute to valvular fibroplasia in humans [1].
• In contrast to two previous reports, however, there was no correlation between plasma levels of fenfluramine and its metabolite norfenfluramine and weight loss, nor was there any correlation between these levels and side effects [2].
• N-(2-Benzoyloxyethyl) norfenfluramine (S-780) was administered to rats by stomach tube at a dose of 50 mg kg-1 of body weight [3].

Psychiatry related information on NORFENFLURAMINE

• Freely-feeding rats were injected with 5-HT or norfenfluramine (NORFENF) directly into the paraventricular hypothalamus (PVN), and precise changes in feeding behavior were monitored by a computer [4].
• 2. In this study, both the syn-9-amino and endo-2-amino isomers, which structurally resemble the gauche conformation of norfenfluramine, were found to have little or no effect on spontaneous locomotor activity [5].

High impact information on NORFENFLURAMINE

• Molecular determinants for the interaction of the valvulopathic anorexigen norfenfluramine with the 5-HT2B receptor [6].
• Supporting this, 1) the binding of norfenfluramine (NF) analogs lacking an S-(+) alpha-methyl group (RNF and alpha-desmethyl-NF) was less sensitive to the V2.53L mutation, and 2) a V2.53A mutation decreased SNF affinity 190-fold, but decreased RNF and alpha-desmethyl-NF affinities only 16- and 45-fold, respectively [6].
• To elucidate the mechanism of "fen-phen"-associated valvular lesions, we examined the interaction of fenfluramine and its metabolite norfenfluramine with 5-HT(2) receptor subtypes and examined the expression of these receptors in human and porcine heart valves [1].
• Binding orientation of amphetamine and norfenfluramine analogues in the benzonorbornene and benzobicyclo[3.2.1]octane ring systems at the active site of phenylethanolamine N-methyltransferase (PNMT) [7].
• Factors controlling the activities of phosphatidate phosphohydrolase and phosphatidate cytidylyltransferase. The effects of chlorpromazine, demethylimipramine, cinchocaine, norfenfluramine, mepyramine and magnesium ions [8].

Biological context of NORFENFLURAMINE

• The effects of intracerebral norfenfluramine on body temperature of the rat [9].
• 5. These differences are due to the efficient deamination of both compounds to polar inactive metabolites in man, with less dealkylation and lower plasma levels of norfenfluramine compared with the other species studied [10].

Anatomical context of NORFENFLURAMINE

• On day 1, plasma and brain fenfluramine levels were higher, and hypothalamus norfenfluramine levels were lower following escalating compared to subacute dosing, although total active drug levels were unaltered [11].
• Fenfluramine and norfenfluramine on glucose uptake into skeletal muscle [12].

Associations of NORFENFLURAMINE with other chemical compounds

• We also demonstrate that MDMA and MDA, like fenfluramine and its N-deethylated metabolite norfenfluramine, elicit prolonged mitogenic responses in human valvular interstitial cells via activation of 5-HT2B receptors [13].
• The influence of acute administration of stereoisomers of fenfluramine and norfenfluramine on the firing rate of central monoaminergic neurons was investigated in rats anaesthetized with chloral hydrate [14].

Gene context of NORFENFLURAMINE

• In contrast, nigral NT levels were unaltered by fenfluramine, intermediately increased by norfenfluramine (148% of control) and maximally increased by METH (267% of control) [15].
• Striatal and nigral substance P (SP) and dynorphin A (Dyn) systems were unaltered by fenfluramine, whereas norfenfluramine caused an intermediate increase in striatal Dyn content but did not significantly alter striatal SP or nigral SP and Dyn levels [15].
• FEN was administered as 0.8 mg/kg to a maximum of 60 mg, and blood was sampled at fixed intervals for prolactin, cortisol, fenfluramine, and norfenfluramine levels [16].
• Effect of norfenfluramine and two structural analogues on brain 5-hydroxyindoles and serum prolactin in rats [17].

Analytical, diagnostic and therapeutic context of NORFENFLURAMINE

• An assay procedure utilizing electron-capture gas chromatography was developed for simultaneous analysis of fenfluramine and norfenfluramine [18].

References