Preclinical profile of befloxatone, a new reversible MAO-A inhibitor

Curet, O.; Damoiseau-Ovens, G.; Sauvage, Caroline; Sontag, N.; Avenet, Patrick; Depoortere, H.; Caille, D.; Bergis, Olivier; Scatton, B.

doi:10.1016/s0165-0327(98)00225-0

Cited by 31 publications

(17 citation statements)

References 61 publications

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“…The first report of an inhibitory effect of a MAO-A inhibitor given acutely is that of Curet et al (1998). The inhibitory effect of befloxatone on serotonergic neurons observed in our experiments is strictly similar to the effect reported by Curet et al (1998). Adell et al (1997) have shown that harmane increases serotonin efflux in the hippocampus, and that this effect might be attributed to an inhibitory effect of harmane on MAO-A.…”

Section: Discussionsupporting

confidence: 88%

“…Later experiments have shown that chronic treatments with MAO-A inhibitors inhibit serotonergic neurons (Blier and de Montigny, 1985;Haddjeri et al 1998) (but the authors did not report the acute effects of these compounds). The first report of an inhibitory effect of a MAO-A inhibitor given acutely is that of Curet et al (1998). The inhibitory effect of befloxatone on serotonergic neurons observed in our experiments is strictly similar to the effect reported by Curet et al (1998).…”

Section: Discussionsupporting

confidence: 88%

“…All the compounds, except befloxatone, were tested at two doses: nicotine, 0.11 and 0.22 mg/kg; harmane, 0.6 and 2.2 mg/kg; norharmane, 0.56 and 2.25 mg/kg; cotinine, 0.52 and 1.98 mg/kg; and selegiline, 0.29 and 0.48 mg/kg. Only one dose of befloxatone was tested, 0.12 mg/kg (which is the dose used by Curet et al 1998). Citalopram (0.08 mg/kg) was used for each successive intravenous (i.v.)…”

Section: Drugsmentioning

confidence: 99%

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Harmane inhibits serotonergic dorsal raphe neurons in the rat

et al. 2005

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Section: Discussionsupporting

confidence: 88%

Section: Discussionsupporting

confidence: 88%

Section: Drugsmentioning

confidence: 99%

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Harmane inhibits serotonergic dorsal raphe neurons in the rat

et al. 2005

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“…Indeed, the study by Miura et al (1996) demonstrated that the reversible monoamine oxidase A inhibitor, moclobomide, induced a further reduction in 5-HT turnover in a number of brain regions of mice exposed to FST. Another reversible monoamine oxidase A inhibitor, befloxatone, also reduced 5-HT turnover in rats (Curet et al 1998). The similarities between the effects of these monoamine oxidase inhibitors and the effect of BU224 on monoamine turnover in control rats and rats exposed to FST are interesting in light of the association between monoamine oxidase and I 2 receptors (CarpØne et al 1995;Tesson et al 1995).…”

Section: Discussionmentioning

confidence: 99%

Behavioral, neuroendocrine and neurochemical effects of the imidazoline I2 receptor selective ligand BU224 in naive rats and rats exposed to the stress of the forced swim test

et al. 2003

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“…The maze consisted of three arms 26 cm in length, 6.1 cm in width, and 15 cm in height. Each arm was subdivided into two equal Curet et al (1996Curet et al ( , 1998. sections.…”

Section: Behavioral Testingmentioning

confidence: 99%

SL25.1131 [3(S),3a(S)-3-Methoxymethyl-7-[4,4,4-trifluorobutoxy]-3,3a,4,5-tetrahydro-1,3-oxazolo[3,4-a]quinolin-1-one], a New, Reversible, and Mixed Inhibitor of Monoamine Oxidase-A and Monoamine Oxidase-B: Biochemical and Behavioral Profile

Aubin

Barnéoud²,

Carter³

et al. 2004

J Pharmacol Exp Ther

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SL25.1131 [3(S),3a(S)-3 -methoxymethyl-7-[4,4,4-trifluorobutoxy]-3,3a,4,5-tetrahydro-1,3-oxazolo[3,4-a]quinolin-1-one] is a new, nonselective, and reversible monoamine oxidase (MAO) inhibitor, belonging to a oxazoloquinolinone series. In vitro studies showed that SL25.1131 inhibits rat brain MAO-A and MAO-B with IC 50 values of 6.7 and 16.8 nM and substratedependent K i values of 3.3 and 4.2 nM, respectively. In ex vivo conditions, the oral administration of SL25.1131 induced a dose-dependent inhibition of MAO-A and MAO-B activities in the rat brain with ED 50 values of 0.67 and 0.52 mg/kg, respectively. In the rat brain, duodenum, and liver, the inhibition of MAO-A and MAO-B by SL25.1131 (3.5 mg/kg p.o.) was reversible, and the recovery of MAO-A and MAO-B activities was complete 16 h after administration. SL25.1131 (3.5 mg/kg p.o.) increased tissue levels of dopamine (DA), norepinephrine, and 5-hydroxytryptamine and decreased levels of their deaminated metabolites 3,4-dihydroxyphenylacetic acid, homovanillic acid, and 5-hydroxyindolacetic acid. In mice, SL25.1131 induced a dose-dependent potentiation of 5-hydroxytryptophan-induced tremors and phenylethylamine-induced stereotypies with ED 50 values of 0.60 and 2.8 mg/kg p.o., respectively. SL25.1131 was able to reestablish normal striatal dopaminergic tone and locomotor activity in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned mice. In addition, when coadministered with L-DOPA, SL25.1131 increased the available DA in the striatum and the duration of L-DOPA-induced hyperactivity. The duration of the effect of L-DOPA on circling behavior in 6-hydroxydopamine-lesioned rats was also increased. The neurochemical profile of SL25.1131 demonstrates that this compound is a mixed, potent, and reversible MAO-A/B inhibitor in vitro, in vivo, and ex vivo. SL25.1131 has therapeutic potential as a symptomatic treatment during the early phase of Parkinson's disease and as an adjunct to L-DOPA therapy during the early and late phases of the disease.Monoamine oxidase (MAO) deaminates monoamine neurotransmitters as well as exogenous amines. Two isoforms of MAO have been described in mammalian tissue, namely, MAO-A and MAO-B, which exhibit different substrate profiles, respond differently to selective inhibitors, and are present in different cellular and subcellular locations. MAO-A preferentially deaminates 5-hydroxytryptamine (serotonin) (5-HT) and norepinephrine (NE) and is selectively inhibited by clorgyline (Johnston, 1968), whereas MAO-B is selectively inhibited by L-deprenyl and preferentially deaminates phenylethylamine (PEA) and benzylamine (Knoll and Magyar, 1972). Dopamine (DA) and tyramine (TYR) are metabolized by both enzyme isoforms (for review, see StrolinBenedetti and Dostert, 1985).Article, publication date, and citation information can be found at

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Preclinical profile of befloxatone, a new reversible MAO-A inhibitor

Cited by 31 publications

References 61 publications

Harmane inhibits serotonergic dorsal raphe neurons in the rat

Harmane inhibits serotonergic dorsal raphe neurons in the rat

Behavioral, neuroendocrine and neurochemical effects of the imidazoline I2 receptor selective ligand BU224 in naive rats and rats exposed to the stress of the forced swim test

SL25.1131 [3(S),3a(S)-3-Methoxymethyl-7-[4,4,4-trifluorobutoxy]-3,3a,4,5-tetrahydro-1,3-oxazolo[3,4-a]quinolin-1-one], a New, Reversible, and Mixed Inhibitor of Monoamine Oxidase-A and Monoamine Oxidase-B: Biochemical and Behavioral Profile

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