Light‐induced Leakage of Spin Label Marker From Liposomes in the Presence of Phototoxic Phenothiazines

Copeland, Edmund S.; Alving, Carl R.; Grenan, Marie M.

doi:10.1111/j.1751-1097.1976.tb06795.x

Cited by 38 publications

(3 citation statements)

References 24 publications

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“…Chlorpromazine is also the phenothiazine that has most definitely been associated with cataract formation (19), which may suggest that the mechanisms of photomutagenesis and cataractogenesis are similar. However, an occasional photosensitized reaction has been reported after the use of nonchlorinated phenothiazines (20), so it appears likely that light can induce active forms with nonchlorinated derivatives as well, although the most photoactive compounds all contain chlorine (12,17,21). Given these considerations and also the relationship between mutagenesis and cancer (8), it would seem prudent to substitute the nonchlorinated phenothiazine derivatives for medical use whenever possible.…”

Section: Discussionmentioning

confidence: 99%

Photomutagenesis by chlorinated phenothiazine tranquilizers.

Jose¹

1979

Proc. Natl. Acad. Sci. U.S.A.

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Phenothiazine tranquilizers are widely used pharmaceuticals that have been associated with side effects, such as formation of cataracts, that seem related to light exposure. Because patients may use them over extensive time periods, it is important to determine what deleterious cellular effects these drugs may cause and, if possible, to select or design drugs that do not cause such effects. The results reported here demonstrate that chlorinated phenothiazine drugs can be photoactivated to mutagenic species, whereas the nonchlorinated analogues do not possess this characteristic. None of the phenothiazines tested is mutagenic in the dark. Mutagenicity was observed only in strains of Salmonella typhimurium that lacked excision repair of DNA, and the mutagenicity was elevated in strains that contained the plasmid pKM101, which may enhance error-prone repair.

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Section: Discussionmentioning

confidence: 99%

Photomutagenesis by chlorinated phenothiazine tranquilizers.

Jose¹

1979

Proc. Natl. Acad. Sci. U.S.A.

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“…This study showed that CPZ ·+ readily inactivates cholinesterase with loss of tryptophan residues. Oxygen is necessary to disrupt liposomes by light in the presence of chlorpromazine (Copeland et al 1976). The presence of oxygen increases the inactivation of Φ‐X174 bacteriophages induced by chlorpromazine (Merville et al 1983b).…”

Section: Discussionmentioning

confidence: 99%

Inactivation of Cholinesterase Induced by Chlorpromazine Cation Radicals

Muraoka

Miura

2003

Pharmacology & Toxicology

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To clarify the mechanism of the side effect of chlorpromazine, we examined the inactivation of cholinesterase induced by chlorpromazine. Cholinesterase was inactivated and its activity was lost in rat serum during interaction of chlorpromazine with horseradish peroxidase and H 2 O 2 . When chlorpromazine was oxidized by horseradish peroxidase and H 2 O 2 , the reaction solution colored pink and the visible absorption spectrum was consistent with the absorption spectrum of the chlorpromazine cation radical (CPZ ¡π ). Adding cholinesterase immediately decreased the pink color of CPZ ¡π , indicating that CPZ ¡π directly attacked cholinesterase to cause loss of the enzyme activity. Tryptophan residues in cholinesterase sharply decreased during the interaction of cholinesterase with horseradish peroxidase and H 2 O 2 . Presumably, loss of tryptophan residues changed the conformation of the cholinesterase protein and then the activity of the enzyme was lost. Other phenothiazine derivatives, including promethazine, triflupromazine, trifluoperazine, trimeprazine, thioridazine and perphenazine, also inactivated cholinesterase during the oxidation by horseradish peroxidase and H 2 O 2 . These results suggest that phenothiazine cation radicals participate in toxicological signs caused by the drugs.

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“…The permeability properties of phospholipidic artificial membranes are pertubated by their UV irradiation in the presence of phenothiazines [163]. Testylier et al [164] studied the photochemical interactions of CPZ with phospholipids and cholesterol in artificial and natural membranes from myelin rat brain.…”

Section: Lipids Photodamagementioning

confidence: 99%

Photosensitization of Biomolecules by Phenothiazine Derivatives

Viola¹,

Dall’Acqua

2006

CDT

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It is well known that many drugs act as photosensitizers towards cells by interacting with various cellular components such as lipids, proteins and nucleic acids. The structural modifications of the cellular components may occur by direct interactions of the excited states (singlets or triplets) of the drugs with the biological substrate or indirectly, through reactive species of oxygen sensitised by the drug themselves. In particular, the phototoxic activity of various drugs correlated with their potential photomutagenic and photocarcinogenic effects, takes place through DNA modification. Phenothiazines, a class of antihistaminic (anti-H1) or neuroleptic drugs used in the therapy of mental illness, such as schizophrenia, organic psychoses and other mental disorders, are known to induce photosensitization of the skin by systemic use or by topical applications as antiallergic drugs. In this review we have focused our attention on the photosensitizing property of phenothiazines and related compounds both in vitro and in vivo systems. Particular attention has been given to the mechanism of photo reaction with biomolecules such as lipids, proteins and DNA. Moreover there is a growing interest in drugs having photobiological effects because of their possible application as phototherapeutics. It has been interesting in this context to mention briefly the possible application of phenothiazine derivatives as new photosensitizers for their therapeutic application in photodynamic therapy (PDT) or in the light inactivation of viruses and bacteria.

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Light‐induced Leakage of Spin Label Marker From Liposomes in the Presence of Phototoxic Phenothiazines

Cited by 38 publications

References 24 publications

Photomutagenesis by chlorinated phenothiazine tranquilizers.

Photomutagenesis by chlorinated phenothiazine tranquilizers.

Inactivation of Cholinesterase Induced by Chlorpromazine Cation Radicals

Photosensitization of Biomolecules by Phenothiazine Derivatives

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