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Titolo:
Stereoselective effect of (R)- and (S)-1-methyl-1,2,3,4-tetrahydroisoquinolines on a mouse model of Parkinson's disease
Autore:
Abe, K; Taguchi, K; Wasai, T; Ren, J; Utsunomiya, I; Shinohara, T; Miyatake, T; Sano, T;
Indirizzi:
Showa Pharmaceut Univ, Dept Neurosci, Tokyo, Japan Showa Pharmaceut Univ Tokyo Japan eut Univ, Dept Neurosci, Tokyo, Japan Showa Pharmaceut Univ, Dept Pharmaceut Chem, Tokyo, Japan Showa PharmaceutUniv Tokyo Japan v, Dept Pharmaceut Chem, Tokyo, Japan
Titolo Testata:
BRAIN RESEARCH BULLETIN
fascicolo: 1, volume: 56, anno: 2001,
pagine: 55 - 60
SICI:
0361-9230(20010901)56:1<55:SEO(A(>2.0.ZU;2-A
Fonte:
ISI
Lingua:
ENG
Soggetto:
RAT-BRAIN; DOPAMINERGIC-NEURONS; TYROSINE-HYDROXYLASE; PREVENTING SUBSTANCE; ENDOGENOUS AMINE; COMPLEX-I; TETRAHYDROISOQUINOLINE; 1-METHYL-1,2,3,4-TETRAHYDROISOQUINOLINE; 1,2,3,4-TETRAHYDROISOQUINOLINE; DERIVATIVES;
Keywords:
Parkinson's disease; 1,2,3,4-tetrahydroisoquinoline; (RS)-1-methyl-1,2,3,4-tetrahydroisoquinoline; (R)-1-methyl-1,2,3,4-tetrahydroisoquinoline; (S)-1-methyl-1,2,3,4-tetrahydroisoquinoline;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
36
Recensione:
Indirizzi per estratti:
Indirizzo: Taguchi, K Showa Pharmaceut Univ, Dept Neurosci, Tokyo, Japan Showa Pharmaceut Univ Tokyo Japan ept Neurosci, Tokyo, Japan
Citazione:
K. Abe et al., "Stereoselective effect of (R)- and (S)-1-methyl-1,2,3,4-tetrahydroisoquinolines on a mouse model of Parkinson's disease", BRAIN RES B, 56(1), 2001, pp. 55-60

Abstract

We carried out behavioral, pathological, and biochemical studies in order to determine whether the stereostructure of 1-methyl-1,2,3,4-tetrahydroisoquinoline (1-MeTIQ) affects the onset of Parkinson's disease-like symptoms, which are induced by 1,2,3,4-tetrahydrolsoquinoline (TIQ) in mice. Pretreatment with (R)-1-MeTIQ or its racemate (RS)-1-MeTIQ prevented the TIQ-induced bradykinesia. Pretreatment with a combination of L-DOPA and carbidopa significantly prevented subsequent TIQ-induced bradykinesia. Furthermore, the pathological study demonstrated that either (R)-1-MeTIQ or its racemate protected against TIO-induced loss of tyrosine hydroxylase-positive cells of the substantia nigra pars compacta. (R)1-MeTIQ and its racemate also prevented the TIO-induced reduction in the levels of dopamine and its metabolites in the striatum. Serotonin and its metabolite were not affected by repeatedadministration of (RS)-1-MeTIQ or its derivatives. On the other hand, (S)-1-MeTIQ induced moderate but significant bradykinesia, whereas (R)-1-MeTIQ did not induce this behavioral abnormality at all. In addition, (S)-enantiomer prevented the onset of TIO-induced bradykinesia, though to a lesser extent than did either (R)-enantiomer or its racemate. However, (S)-enantiomerdid not prevent the loss of tyrosine hydroxylase-positive neurons in the substantia nigra pars compacta. We concluded that (R)-1-MeTIQ, and not (S)-enantiomer, plays a crucial role in protection against TIQ-induced parkinsonism, a fact which suggests that enantiomeric biochemical events such as 1-MeTIQ biosynthesis may participate in the pathogenesis of Parkinson's disease. (C) 2001 Elsevier Science Inc.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 29/02/20 alle ore 14:27:38