Photochemical Reactions Involved in the Phototoxicity of the Anticonvulsant and Antidepressant Drug Lamotrigine (Lamictal®)

• Published in: Photochemistry and photobiology Vol. 85; no. 6; pp. 1327 - 1335
• Main Authors: Bilski, Piotr J., Wolak, M. A., Zhang, V., Moore, D. E., Chignell, C. F.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.11.2009
• Subjects: Anticonvulsants - chemistry; Anticonvulsants - toxicity; Antidepressants; Antidepressive Agents - chemistry; Antidepressive Agents - toxicity; Chemical reactions; Dermatitis, Phototoxic; Humans; Photochemistry; Photosensitizing Agents - chemistry; Proteins; Singlet Oxygen; Spectrum Analysis; Toxicity; Triazines - adverse effects; Triazines - chemistry; Triazines - toxicity
• ISSN: 0031-8655; 1751-1097
• DOI: 10.1111/j.1751-1097.2009.00590.x

Lamotrigine (LTG) [3,5‐diamino‐6‐(2,3‐dichlorophenyl)‐1,2,4‐triazine], an anticonvulsant and antidepressant drug Lamictal®, produces a (photo)toxic response in some patients. LTG absorbs UV light, generating singlet oxygen (1O2) with a quantum yield of 0.22 in CH2Cl2, 0.11 in MeCN and 0.01 in D2O. A small production of superoxide radical anion was also detected in acetonitrile. Thus, LTG is a moderate photosensitizer producing phototoxicity and oxidizing linoleic acid. LTG is a weak 1O2 quencher (kq = 3.2 × 105 m−1 s−1 in MeCN), but its photodecomposition products in dimethyl sulfoxide (DMSO) quenched 1O2 very efficiently. Upon intense UV irradiation from a xenon lamp, LTG was photobleached rapidly in DMSO and slowly in acetonitrile, alcohol and water. The rate increased significantly when laser pulses at 266 nm were employed. The photobleaching products generated 1O2 twice as strongly as LTG. Photobleaching was usually accompanied by the release of chloride anions, which increased in the presence of ascorbic acid. This suggests the formation of aryl radicals via dechlorination, a process which may be responsible for the photoallergic response observed in some patients. Our results demonstrate that LTG is a moderate generator of 1O2 prone to photodechlorination, especially in a reducing environment, which can contribute to the reported phototoxicity of LTG.