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Titolo:
DEVELOPMENT OF FLUORINATED 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE ANALOGS WITH POTENT NIGROSTRIATAL TOXICITY FOR POTENTIAL USE IN POSITRON EMISSION TOMOGRAPHY STUDIES
Autore:
HARIK SI; RIACHI NJ; HRITZ MA; BERRIDGE MS; SAYRE LM;
Indirizzi:
UNIV HOSP CLEVELAND,DEPT NEUROL,2074 ABINGTON RD CLEVELAND OH 44106 CASE WESTERN RESERVE UNIV,SCH MED,DEPT RADIOL CLEVELAND OH 44106 CASE WESTERN RESERVE UNIV,SCH MED,DEPT CHEM CLEVELAND OH 44106 CASE WESTERN RESERVE UNIV,SCH MED,DEPT NEUROL CLEVELAND OH 44106
Titolo Testata:
The Journal of pharmacology and experimental therapeutics
fascicolo: 2, volume: 266, anno: 1993,
pagine: 790 - 795
SICI:
0022-3565(1993)266:2<790:DOF1>2.0.ZU;2-Z
Fonte:
ISI
Lingua:
ENG
Soggetto:
MONOAMINE OXIDASE-A; DOPAMINERGIC NEUROTOXIN 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE; PARKINSONS-DISEASE; PRIMATE BRAIN; BIOLOGICAL-ACTIVITY; MAO-A; MPTP; INHIBITORS; METABOLITE; MECHANISM;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
41
Recensione:
Indirizzi per estratti:
Citazione:
S.I. Harik et al., "DEVELOPMENT OF FLUORINATED 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE ANALOGS WITH POTENT NIGROSTRIATAL TOXICITY FOR POTENTIAL USE IN POSITRON EMISSION TOMOGRAPHY STUDIES", The Journal of pharmacology and experimental therapeutics, 266(2), 1993, pp. 790-795

Abstract

The discovery of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) toxicity stimulated intense interest in neurotoxicology and in the possible toxic etiology of Parkinson's disease. Better understanding of MPTP neurotoxicity may be achieved by studies using F-18-radiolabeled MPTP analogs and positron emission tomography in nonhuman primates. We synthesized three fluorinated analogs of MPTP: thyl-4-(2-fluorophenyl)-1,2,3,6-tetrahydropyridine (2'-F-MPTP), rifluorome-thyl)phenyl]-1,2,3,6-tetrahydropyridine (2'-CF3-MPTP) and 2-(fluoromethyl)phenyl]-1,2,3,6-tetrahydropyridine (2'-CH2F-MPTP), and developed a method for preparing the latter in F-18-labeled form. We now studied the suitability of2'-CH2F-MPTP and its hydrolysis products as substrates for monoamine oxidase (MAO) from mouse and monkey brain preparations, and investigated the neurotoxic effect of 2'-CH2F-MPTP and 2'-F-MPTP on the nigrostriatal dopaminergic system in mice. We found that 2'-CH2F-MPTP is a better substrate for MAO and that both 2'-CH2F-MPTP and 2'-F-MPTP were more potent neurotoxins than MPTP. Like MPTP, 2'-F-MPTP was exclusively oxidized by MAO-B and its toxicity blocked by pargyline or deprenyl but not by clorgyline. In contrast, 2'-CH2F-MPTP was oxidized by both MAO-A and MAO-B, and its toxicity was not blocked by pargyline, clorgyline or deprenyl when given separately, but required clorgyline and deprenyl together.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/07/20 alle ore 08:44:05