@article{oai:kanazawa-u.repo.nii.ac.jp:00015316,
 author = {Kawahara, Masami and Ishida, Tomoyuki and Emoto, Chie and Matsushita, Ryo and Ichimura, Fujio and Kataoka, Osamu and Mukai, Chisato and Hanaoka, Miyoji and Ishizaki, Junko and Miyamoto, Kenichi},
 issue = {1},
 journal = {臨床薬理 = Japanese journal of clinical pharmacology},
 month = {Jan},
 note = {The anticancer drug, dacarbazine, is known to be photosensitive, and its photodegradation products have been pointed out as the causes of side effects including local venous pain of injection site. In this study, we attempted to clarify the causative substance of pain after photodegradation of dacarbazine. We synthesized five photodegradation products of dacarbazine; dimethylamine, 5-diazoimidazole-4-carboxamide (Diazo-IC), 4-carbamoylimidazolium-5-olate, 4-carbamoyl-2-(4-carbamoylimidazol-5-ylazo) imidazolium-5-olate and 2-azahypoxanthine, and examined pain reactions induced by these substances in mice. Mice were intraperitoneally administered each photodegradation product, then number of stretching reactions or writhing reactions as types of pain behaviors was counted. Only Diazo-IC clearly induced the pain reactions in mice in a concentration-dependent manner: the other products caused no pain reaction. The pain threshold of Diazo-IC in mice was estimated at between 0.1 mg/ml and 0.2 mg/ml. While diclofenac sodium significantly reduced acetic acid-induced pain reactions in mice, it did not influence the reactions induced by Diazo-IC. This result suggests that Diazo-IC-induced pain reactions represent a different mechanism from acetic acid-induced inflammatory pain. Degradation rate constant of 0.1 mg/ml of dacarbazine solution was 10 times larger than 1 mg/ml of dacarbazine. Dacarbazine solution for drip infusion should be sufficiently shielded from light.},
 pages = {15--22},
 title = {Determination of a pain substance produced by the photodegradation of dacarbazine},
 volume = {32},
 year = {2001}
}