Primary photochemical processes of the phototoxic neuroleptic cyamemazine: a study by laser flash photolysis and steady-state irradiation.
The photophysical and photochemical properties of the UV-A-absorbing phototoxic drug cyamemazine (CMZ) (2-cyano-10-(3-[dimethylamino]-2-methyl-propyl)-phenothiazine) have been investigated in neutral buffered aqueous solutions. The transient absorbances of the hydrated electrons, of the first excited triplet state (3CMZ*) with a characteristic absorption band peaking at 420 nm and of the radical cation (*CMZ+) (maximum absorbance at 500 nm) have been observed by 355 nm laser flash spectroscopy of deaerated solutions. All these transient species are formed by monophotonic processes and react with oxygen. Bimolecular reaction rate constants of *CMZ+ and 3CMZ* with O2 are 2 x 10(7) M(-1) s(-1) and 4 x 10(9) M(-1) s(-1), respectively. The 3CMZ* reacts only sluggishly (reaction rate constant, 9 x 10(6) M(-1) s(-1)) with tryptophan chosen as a Type-I photodynamic substrate. Steady-state irradiations with 365 nm light demonstrate that CMZ is rapidly photolyzed (quantum yield, 0.04) in O2-saturated solutions leading to oxidation of the sulfur atom and of the side-chain nitrogen of CMZ. This photoproduct (2-cyano-10-(3-[dimethylamino, N-oxide]-2-methyl-propyl)-5-oxide-phenothiazine), is a good Type-I and Type-II photodynamic photosensitizer producing singlet oxygen in high yield (approximately 0.45) and could play a major role in the phototoxicity of CMZ.
Morlière
Patrice
P
Institut de Recherche sur la Peau, Unité INSERM 532, Hôpital Saint-Louis, Paris, France.
Bosca
Francisco
F
Miranda
Miguel A
MA
Castell
José V
JV
Santus
René
R
D002851:Chromatography, High Pressure Liquid; D015394:Molecular Structure; D009474:Neurons / Q000187:drug effects* / Q000528:radiation effects*; D010640:Phenothiazines / Q000737:chemistry / Q000633:toxicity*; D010782:Photolysis; D017319:Photosensitizing Agents / Q000737:chemistry / Q000633:toxicity; D012996:Solutions; D013057:Spectrum Analysis
D010640:Phenothiazines; D017319:Photosensitizing Agents; D012996:Solutions; C028457:cyamemazine