Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
STUDIES ON THE INTERACTION OF ROXINDOLE WITH BRAIN MONOAMINE OXIDASESAND DOPAMINERGIC-NEURONS IN-VITRO AND IN-VIVO
Autore:
SEYFRIED CA; ADAM G;
Indirizzi:
E MERCK AG,DEPT CNS RES,BIOL RES D-64271 DARMSTADT GERMANY
Titolo Testata:
Pharmacology & toxicology
fascicolo: 6, volume: 74, anno: 1994,
pagine: 314 - 320
SICI:
0901-9928(1994)74:6<314:SOTIOR>2.0.ZU;2-E
Fonte:
ISI
Lingua:
ENG
Soggetto:
1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE (MPTP)-INDUCED NEUROTOXICITY; BIOLOGICAL-ACTIVITY; PYRIDINIUM METABOLITES; TISSUE CONCENTRATIONS; STRIATAL DOPAMINE; MPTP ANALOGS; AGONIST; MPP+; MICE; IDENTIFICATION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
27
Recensione:
Indirizzi per estratti:
Citazione:
C.A. Seyfried e G. Adam, "STUDIES ON THE INTERACTION OF ROXINDOLE WITH BRAIN MONOAMINE OXIDASESAND DOPAMINERGIC-NEURONS IN-VITRO AND IN-VIVO", Pharmacology & toxicology, 74(6), 1994, pp. 314-320

Abstract

Roxindole, a structurally novel psychotropic indolylbutyl-4-phenyltetrahydropyridine, was studied with respect to the formation of potentially neurotoxic pyridinium metabolites in comparison to MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine). In contrast to MPTP, roxindole failed to serve as a substrate for monoamine oxidases (MAO) from mouse,monkey and human brain in vitro. Accordingly, neither the putative MAO-oxidation product of roxindole (ROX(+)) nor MPP(+) (1-methyl-4-phenylpyridinium ion) was detected in mouse striatum after high subcutaneous doses of roxindole in spite of the presence of similar to 6 mu g of roxindole per g of striatum in these animals. After multiple subcutaneous treatments with 95.2 mg/kg roxindole, no long-term striatal dopamine depletions were observed in contrast to MPTP. Furthermore, unlike MPP(+), ROX(+) did not induce release of previously accumulated H-3-dopamine in mouse striatal slices indicating that ROX(+) cannot utilize the dopamine uptake carrier to enter neurones. ROX(+) at doses up to 100 mg/kg subcutaneously failed to alter striatal biogenic amine levels and gross behaviour of mice. Thus, no MPTP-like neurotoxic metabolitesare formed from roxindole in vivo and neurotoxic effects of ROX(+), even if formed in minute amounts by some MAO-independent pathway, are highly unlikely.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 10/07/20 alle ore 15:47:46