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Titolo:
The mechanisms involved in the long-lasting neuroprotective effect of fluoxetine against MDMA ('ecstasy')-induced degeneration of 5-HT nerve endings in rat brain
Autore:
Sanchez, V; Camarero, J; Esteban, B; Peter, MJ; Green, AR; Colado, MI;
Indirizzi:
Univ Complutense Madrid, Fac Med, Dept Pharmacol, E-28040 Madrid, Spain Univ Complutense Madrid Madrid Spain E-28040 acol, E-28040 Madrid, Spain De Montfort Univ, Pharmacol Res Grp, Sch Pharm, Leicester LE1 9BH, Leics, England De Montfort Univ Leicester Leics England LE1 9BH LE1 9BH, Leics, England Astrazeneca R&D Charnwood, Loughborough LE11 9BH, Leics, England Astrazeneca R&D Charnwood Loughborough Leics England LE11 9BH cs, England
Titolo Testata:
BRITISH JOURNAL OF PHARMACOLOGY
fascicolo: 1, volume: 134, anno: 2001,
pagine: 46 - 57
SICI:
0007-1188(200109)134:1<46:TMIITL>2.0.ZU;2-7
Fonte:
ISI
Lingua:
ENG
Soggetto:
H-3 PAROXETINE BINDING; 3,4-METHYLENEDIOXYMETHAMPHETAMINE MDMA; SEROTONIN TRANSPORTERS; P-CHLOROAMPHETAMINE; METHYLENEDIOXYMETHAMPHETAMINE MDMA; 3,4-METHYLENEDIOXYAMPHETAMINE MDA; ANTIDEPRESSANT TREATMENTS; MEDIATED RELEASE; TRANSGENIC MICE; ECSTASY;
Keywords:
3,4-methylenedioxymethamphetamine; ecstasy; neuroprotection; 5-hydroxytryptamine; fluoxetine; norfluoxetine; fluvoxamine;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
73
Recensione:
Indirizzi per estratti:
Indirizzo: Colado, MI Univ Complutense Madrid, Fac Med, Dept Pharmacol, E-28040 Madrid, Spain Univ Complutense Madrid Madrid Spain E-28040 40 Madrid, Spain
Citazione:
V. Sanchez et al., "The mechanisms involved in the long-lasting neuroprotective effect of fluoxetine against MDMA ('ecstasy')-induced degeneration of 5-HT nerve endings in rat brain", BR J PHARM, 134(1), 2001, pp. 46-57

Abstract

1 It has been reported that co-administration of fluoxetine with 3,4-methylenedioxymethaniphetamine (MDMA. 'ecstasy') prevents MDMA-induced degeneration of 5-HT nerve endings in rat brain. The mechanisms involved have now been investigated.2 MDMA (15 mg kg(-1), i.p.) administration produced a neurotoxic loss of 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) in cortex, hippocampus and striatum and a reduction in cortical [H-3]-paroxetine binding 7 days later. Fluoxetine (10 mg kg(-1), i.p., x 2, 60 min apart) administered concurrently with MDMA or given 2 and 4 days earlier provided complete protection, and significant protection when given 7 days earlier. Fluvoxamine (15 mg kg(-1), i.p., x 2, 60 min apart) only produced neuroprotection when administered concurrently.3 Fluoxetine (10 mg kg(-1), x 2) markedly increased the K-D and reduced the B-max of cortical [H-3]-paroxetine binding 2 and 4 days later. The B-max was still decreased 7 days later, but the KD was unchanged. [H-3]-Paroxetine binding characteristics were unchanged 24 h after fluvoxamine (15 mg kg(1), x 2).4 A significant cerebral concentration of fluoxetine Plus norfluoxetine was detected over the 7 days following fluoxetine administration. The fluvoxamine concentration had decreased markedly by 24 h.5 Pretreatment with fluoxetine (10 mg kg(-1), x 2) failed to alter cerebral MDMA accumulation compared to saline pretreated controls.6 Neither fluoxetine or fluvoxamine altered MDMA-induced acute hyperthermia.7 These data demonstrate that fluoxetine produces long-lasting protection against MDMA-induced neurodegeneration. an effect apparently related to thepresence of the drug and its active metabolite inhibiting the 5-HT transporter. Fluoxetine does not alter the metabolism of MDMA or its rate of cerebral accumulation.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 25/01/20 alle ore 07:14:32