title: Effect of intracerebral hydroxytyrosol and its nitroderivatives on striatal dopamine metabolism: A study by in vivo microdialysis.
abstract: OBJECTIVE
  The natural phenolic oil compound hydroxytyrosol (HTy) is widely studied because of its antioxidant and neuroprotective properties. Nitroderivatives of HTy have been studied in order to evaluate their putative effects on catechol-O-methyltransferase (COMT) activity.
  
  
  METHODS
  To study its effect on dopamine metabolism, nitrohydroxytyrosol and its lipophilic derivatives (nitrohydroxytyrosyl acetate and ethyl nitrohydroxytyrosyl ether), were administered into the rat corpus striatum through a microdialysis probe. Other catechols (HTy and the known COMT inhibitor Ro 41-0960) were also studied for comparison.
  
  
  RESULTS
  The olive oil phenolic compounds (nitroderivatives and HTy) increased extracellular levels of 3,4-dihydroxyphenylacetic acid during the perfusion with similar maximum values to that of Ro 41-0960 when comparing to basal dialysate levels (approximately 140%). None of the compound series produced a decrease in the homovanillic acid extracellular levels below 75%. Among all novel compounds studied, both lipophilic nitrocatechols (nitrohydroxytyrosyl acetate and ethyl nitrohydroxytyrosyl ether) showed a long-acting effect over time once the perfusion through the microdialysis probe ended.
  
  
  CONCLUSIONS
  In accordance with the actual design of novel COMT inhibitors with a long profile, our results suggest a certain influence of the side chain substituent on the COMT activity that could provide new lipophilic COMT inhibitors.
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, University of Seville, 41012 Seville, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Gallardo
authors.affiliation: Department of Organic and Pharmaceutical Chemistry, Faculty of Pharmacy, University of Seville, 41012 Seville, Spain.
authors.forename: Andrés
authors.initials: A
authors.lastname: Madrona
authors.affiliation: Department of Organic and Pharmaceutical Chemistry, Faculty of Pharmacy, University of Seville, 41012 Seville, Spain.
authors.forename: Rocío
authors.initials: R
authors.lastname: Palma-Valdés
authors.affiliation: Department of Organic and Pharmaceutical Chemistry, Faculty of Pharmacy, University of Seville, 41012 Seville, Spain.
authors.forename: José Luis
authors.initials: JL
authors.lastname: Espartero
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, University of Seville, 41012 Seville, Spain. Electronic address: msantiago@us.es.
authors.forename: Marti
authors.initials: M
authors.lastname: Santiago
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000493:pharmacokinetics / Q000494:pharmacology; D001577:Benzophenones / Q000494:pharmacology; D002394:Catechol O-Methyltransferase / Q000378:metabolism; D065098:Catechol O-Methyltransferase Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology; D003342:Corpus Striatum / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000975:Antioxidants; D001577:Benzophenones; D065098:Catechol O-Methyltransferase Inhibitors; C005975:3,4-dihydroxyphenylethanol; C071721:Ro 41-0960; D002394:Catechol O-Methyltransferase; D010626:Phenylethyl Alcohol; D004298:Dopamine
keywords: Catechol-O-methyltransferase inhibitors; Dopamine metabolism; Hydroxytyrosol; In vivo microdialysis; Nitrocatechols; Rat's striatum