PMID: 43893Dec 1, 1979

Effect of structure on phenothiazine cation radical reactions in aqueous buffers

Journal of Medicinal Chemistry
P H Sackett, R L McCreery

Abstract

The reactions of the cation radicals of 11 phenothiazine tranquilizers were examined in mildly acidic aqueous buffers. Of the 11, those having an aminopropyl side chain in the 10 position reacted to form 0.5 mol of sulfoxide and 0.5 mol of parent drug per mole of initial radical. Cation radicals with different side chains react to form additional products, which remain to be identified but probably result from hydroxylation of the phenothiazine ring. The decay kinetics of three of the cation radicals undergoing reactions with known stoichiometry, namely, chloropromazine, promazine, and triflupromazine, were studied in detail, and it was concluded that they all react via the same mechanism. The mechanism involves attack of the cation radical by a nucleophile, and radicals with electron-withdrawing groups in the 2 position react more quickly. Since the cation radicals with faster reaction rates with nucleophiles are more pharmacologically active, it is hypothesized that the cation radical-nucleophile interaction may be responsible for binding of phenothiazines to receptor proteins.

References

Dec 1, 1996·Journal of Pharmaceutical and Biomedical Analysis·Z SentürkI Biryol
Sep 1, 1985·Photochemistry and Photobiology·J MarkoA Lablache-Combier
Jun 21, 1985·Pharmaceutisch Weekblad. Scientific Edition·N J De Mol, J Koenen
Nov 8, 2005·Analytical Sciences : the International Journal of the Japan Society for Analytical Chemistry·Helena Puzanowska-TarasiewiczKatarzyna Mielech-Lukasiewicz
Feb 26, 2013·Chemphyschem : a European Journal of Chemical Physics and Physical Chemistry·Cécile BizeMuriel Blanzat
Oct 11, 2011·International Journal of Pharmaceutics·Urszula DomańskaAneta Pobudkowska
May 1, 2007·Archives of Biochemistry and Biophysics·Edyta Madej, Peter Wardman
Aug 1, 1983·Photochemistry and Photobiology·J MarkoA Lablache-Combier

Related Concepts

Antipsychotic Effect
Structure-Activity Relationship
Free Radicals
Cations
Phenothiazines

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