title: Horseradish peroxidase-catalyzed sulfoxidation of promethazine and properties of promethazine sulfoxide.
abstract: Promethazine sulfoxide was obtained with a quantitative yield in a horse radish peroxidase-catalyzed reaction of promethazine and hydrogen peroxide and was also prepared by direct chemical synthesis. The enzymatic sulfoxidation of promethazine was studied in vitro as a function of pH, promethazine, and hydrogen peroxide concentration. Promethazine sulfoxide inhibits with an apparent K(i) of 59.7 microM at pH 5.5 the enzymatic reaction, followed spectrophotometrically, polarographically, potentiometrically, and luminometrically. The reaction was also inhibited by ascorbic acid (K(i) 26.8 microM) and glutathione (K(i) 41.8 microM). The spectrophotometric techniques employed, together with ESR spectrometry, allowed the identification of at least three radical species formed in the course of the reaction. Promethazine sulfoxide is devoid of the antioxidant effect exhibited by promethazine on rat brain synaptosomes. The sulfoxide also lacks photosensitizing action, while retaining the neuroleptic effect of the parent compound.
authors.affiliation: Department of Biological Chemistry, University of Padua, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Galzigna
authors.forename: V
authors.initials: V
authors.lastname: Rizzoli
authors.forename: M P
authors.initials: MP
authors.lastname: Schiappelli
authors.forename: M P
authors.initials: MP
authors.lastname: Rigobello
authors.forename: M
authors.initials: M
authors.lastname: Scarpa
authors.forename: A
authors.initials: A
authors.lastname: Rigo
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001205:Ascorbic Acid / Q000494:pharmacology; D001463:Barbiturates / Q000494:pharmacology; D001921:Brain / Q000378:metabolism; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals / Q000378:metabolism; D006735:Horseradish Peroxidase / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000378:metabolism; D007700:Kinetics; D015227:Lipid Peroxidation / Q000187:drug effects; D008163:Luminescent Measurements; D008297:Male; D010101:Oxygen Consumption / Q000187:drug effects; D010640:Phenothiazines / Q000378:metabolism; D011398:Promethazine / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012890:Sleep / Q000187:drug effects; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
chemical_list: D000975:Antioxidants; D001463:Barbiturates; D005609:Free Radicals; D010640:Phenothiazines; C103202:promethazine sulfoxide; D006861:Hydrogen Peroxide; D006735:Horseradish Peroxidase; D011398:Promethazine; D001205:Ascorbic Acid