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  • Title: d- and l-isomers of fenfluramine differ markedly in their interaction with brain serotonin and catecholamines in the rat.
    Author: Invernizzi R, Berettera C, Garattini S, Samanin R.
    Journal: Eur J Pharmacol; 1986 Jan 14; 120(1):9-15. PubMed ID: 3485052.
    Abstract:
    Various doses of fenfluramine isomers were compared for their ability to affect monoamine levels, metabolism and synthesis in the rat brain. d-Fenfluramine was more potent than l-fenfluramine in reducing serotonin (5-HT) and 5-hydroxy-indoleacetic acid (5-HIAA) at 4 h after their administration. After decarboxylase inhibition, a low dose of d-fenfluramine (2.5 mg/kg) reduced 5-HT synthesis, assessed as 5-hydroxytryptophan (5-HTP) accumulation, in the hypotalamus and lower brain-stem only, whereas a higher dose (5 mg/kg) reduced 5-HT synthesis in all brain regions examined except the striatum. A higher dose of l-fenfluramine (10 mg/kg) was required to reduce 5-HT synthesis. Metergoline, a 5-HT antagonist, did not modify the effects of fenfluramine isomers on 5-HT synthesis. One h after its administration l-fenfluramine 5-20 mg/kg significantly increased brain 3-methoxy-4-hydroxyphenylethylene glycol sulfate (MHPG-SO4), striatal homovanillic acid (HVA) and dihydroxyphenylacetic acid (DOPAC) levels, while after 4 h only the highest dose raised HVA levels. No change of striatal HVA and DOPAC levels was seen 1 or 4 h after any dose of d-fenfluramine while the highest dose raised brain MHPG-SO4 levels. Neither l- nor d-fenfluramine changed striatal 3-methoxytyramine (3-MT) levels. The noradrenaline (NA) and dopamine (DA) levels were decreased 4 h after 10 and 20 mg/kg l-fenfluramine or 20 mg/kg d-fenfluramine. The results show that the d- and l-isomers of fenfluramine at relatively low doses have a specific action on brain 5-HT and catecholamines, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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