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Titolo:
Comparative toxicological study on the hepatic safety of entacapone and tolcapone in the rat
Autore:
Haasio, K; Sopanen, L; Vaalavirta, L; Linden, IB; Heinonen, EH;
Indirizzi:
Orion Corp, Res, Orion Pharma, FIN-02101 Espoo, Finland Orion Corp EspooFinland FIN-02101 rion Pharma, FIN-02101 Espoo, Finland Univ Helsinki, Cent Hosp, Dept Oncol, FIN-00014 Helsinki, Finland Univ Helsinki Helsinki Finland FIN-00014 ol, FIN-00014 Helsinki, Finland
Titolo Testata:
JOURNAL OF NEURAL TRANSMISSION
fascicolo: 1, volume: 108, anno: 2001,
pagine: 79 - 91
SICI:
0300-9564(2001)108:1<79:CTSOTH>2.0.ZU;2-O
Fonte:
ISI
Lingua:
ENG
Soggetto:
CATECHOL-O-METHYLTRANSFERASE; PARKINSONS-DISEASE; COMT INHIBITORS; LEVODOPA;
Keywords:
COMT inhibitor; entacapone; tolcapone; hepatotoxicity; levodopa; Parkinson's disease; uncoupling;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
24
Recensione:
Indirizzi per estratti:
Indirizzo: Haasio, K Orion Corp, Res, Orion Pharma, POB 65, FIN-02101 Espoo, Finland Orion Corp POB 65 Espoo Finland FIN-02101 -02101 Espoo, Finland
Citazione:
K. Haasio et al., "Comparative toxicological study on the hepatic safety of entacapone and tolcapone in the rat", J NEURAL TR, 108(1), 2001, pp. 79-91

Abstract

Entacapone and tolcapone are novel COMT (catechol-O-methyltransferase) inhibitors indicated for the adjunctive treatment of Parkinson's disease (PD) in combination with levodopa. The marketing authorisation of tolcapone was suspended in the European Union (EU) in 1998 mainly due to severe abnormal hepatic reactions. This fact raised concern about the safety of COMT inhibitors in the treatment of parkinsonian patients. In order to investigate whether these COMT inhibitors exhibit different effects on the liver comparative toxicological studies were performed in the rat. Short term toxicological studies in rats at high oral doses of entacapone and tolcapone (200, 400 or 600mg/kg daily) were carried out. Tolcapone (400mg/kg/day or 600mg/kg/day) increased mortality after only one week treatment and induced signs of toxicity such as a rise in body temperature, stimulation of respiration and rapid onset of rigor mortis after death. Entacapone did not show any adverse effects at the tested dose levels. In the histopathological examination liver cell necrosis was observed in the tolcapone (400 and 600mg/kg/day) treated rats, but it revealed no treatment relatedsigns of toxicity in entacapone-treated rats. We conclude that the toxicological profile of the two COMT inhibitors, entacapone and tolcapone, differfrom each other, tolcapone - unlike entacapone - showed hepatotoxicity.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/04/20 alle ore 09:11:20