Isolation and identification of the photodegradation products of the photosensitizing antidepressant drug clomipramine. Phototoxicity studies on erythrocytes.
The isolation and identification of the photodegradation products of clomipramine (CIP) in phosphate buffered saline (PBS pH 7.4 and 6.0) solution and methanol under aerobic conditions were studied. Six compounds were identified and four of them were isolated and characterized by spectroscopic methods. A radical mechanism with the participation of the solvent is proposed for the photodegradation of CIP which undergoes homolytic cleavage of the carbon-chlorine bond and also photooxidation of the amine group. CIP was able to induce photohemolysis when it was irradiated in PBS pH 7.4 and in PBS pH 6.0 containing a suspension of human red blood cells (RBCs). The photohemolysis experiments in the presence of additives DABCO and GSH showed nearly total inhibition of drug-induced photohemolysis. The efficient inhibition of photohemolysis by the radical scavenger GSH compared with the inhibition show by DABCO suggests a moderate effect by singlet oxygen. Clomipramine-N-oxide was the unique photoproduct able to induce hemolysis and photohemolysis when it was incubated and irradiated with RBCs for 1 h. A mechanism involving singlet oxygen, radicals and photoproducts is suggested for the reported phototoxicity.
Laboratorio de Fotoquímica y Fotobiología, Departamento de Química, Universidad Simón Bolívar, Caracas, Venezuela. ncanudas@usb.ve
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D000332:Aerobiosis; D000929:Antidepressive Agents, Tricyclic / Q000737:chemistry* / Q000528:radiation effects; D002997:Clomipramine / Q000737:chemistry* / Q000528:radiation effects; D017484:Dermatitis, Phototoxic / Q000097:blood*; D004912:Erythrocytes / Q000187:drug effects*; D006461:Hemolysis / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D010777:Photochemistry; D010782:Photolysis; D014466:Ultraviolet Rays
D000929:Antidepressive Agents, Tricyclic; D002997:Clomipramine