Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2002-2-11
pubmed:abstractText
This work concerns a combined photophysical, photochemical and photobiological study of three drugs (psychotherapeutic agents) of the phenothiazine series: perphenazine, fluphenazine hydrochloride and thioridazine hydrochloride. The excited-state properties were first investigated by stationary and time-resolved fluorimetry and by laser flash photolysis. The spectral description was assisted by quantum-mechanical calculations with the INDO/1-CI method. In organic media the lowest excited singlet state was found to decay by fluorescence (small quantum yield) and mainly by intersystem crossing to the lowest triplet state, which is responsible for oxygen photosensitization (high yields of singlet oxygen production) and photodegradation. A further decay pathway in aqueous solutions was the photoionization process, which led to the formation of the phenothiazine radical cations and the solvated electron. After the preliminary study of the photobehavior in organic solvents and in water, the phototoxicity of the three drugs was investigated on various biological substrates through a series of in vitro assays under UVA irradiation. Photohemolysis of mouse erythrocytes and phototoxicity on cultured murine fibroblasts were observed for all three compounds. Lipid photoperoxidation was then investigated using linoleic acid as the unsaturated lipid model and isolated red blood cell membranes. The drug-induced photodamage was also evaluated on proteins by measuring the photosensitizing cross-linking in erythrocyte ghosts. The combined approach proved to be useful in understanding the mechanism by which these phenothiazine derivatives induce skin photosensitization. In particular, the photophysical properties of the compounds under investigation and the results of the study on their phototoxicity are in agreement with a mechanism that involves the radical cation of the drugs as a main intermediate.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0031-8655
pubmed:author
pubmed:issnType
Print
pubmed:volume
75
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
11-21
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Excited-state properties and in vitro phototoxicity studies of three phenothiazine derivatives.
pubmed:affiliation
Department of Chemistry, University of Perugia, Italy. elisei@phch.chm.unipg.it
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't