Photooxidation mechanism of levomepromazine in different solvents.
Photooxidation mechanism of levomepromazine in different solvents.
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左美丙嗪在不同溶剂中的光氧化机理。
DOI：
10.1111/php.12147
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发表时间：
2013
影响因子：
3.3
通讯作者：
Miranda,MiguelA
中科院分区：
文献类型：
--
作者：
Piñero-Santiago,LuisE;García,Carmelo;Lhiaubet-Vallet,Virginie;Trzcionka,Jerome;Oyola,Rolando;Torres,Karen;Leguillú,Jaysika;Miranda,MiguelA
不想要的光诱导反应是大多数丙氨酸类药物众所周知的不良反应，包括左旋丙嗪(LPZ、左旋丙氨酸®或诺齐南®)。这种药物在精神病学中主要用于治疗精神分裂症和其他分裂情感障碍。左旋丙嗪的特殊镇静性能使其特别适合用于精神科重症监护。然而，在好氧条件下，它在UV-A和UV-B光下是不耐光的，从而形成了它的亚砜。LPZ在乙腈(MeCN)中的光化学与在甲醇(MeOH)和磷酸盐缓冲溶液(PBS，pH=87.4)中的光化学完全不同。在好氧条件下，PBS和MeOH中的主要光产物是左旋丙氨亚砜(LPZSO)，但在水环境中其含量要高得多。不能表征相应的MeCN中的主要光产物。LPZ在PbS、甲醇和乙腈中的破坏量子产率分别为0.13、0.02和~lt；10−3。进一步证明了LPZSO不是由单重态氧与基态LPZ反应形成的。该氧化产物实际上是LPZ(LPZ·+)的阳离子自由基与分子氧反应生成的。这个阳离子自由基是通过3LPZ*和基态分子氧之间的电子转移过程产生的。
Unwanted photoinduced responses are well‐known adverse effects of most promazine drugs, including levomepromazine (LPZ, Levoprome®or Nozinan®). This drug is indicated in psychiatry primarily for the treatment of schizophrenia and other schizoaffective disorders. Levomepromazine's particular sedative properties make it especially fit for use in psychiatric intensive care. Nevertheless, it is photolabile under UV‐A and UV‐B light in aerobic conditions resulting in the formation of its sulfoxide. The LPZ photochemistry in acetonitrile (MeCN) is completely different from that in methanol (MeOH) and phosphate buffer solutions (PBS, pH = 7.4). The major photoproduct in PBS and MeOH under aerobic conditions is levomepromazine sulfoxide (LPZSO), although the amount is considerably higher in the aqueous environment. The corresponding main photoproduct in MeCN could not be characterized. The destruction quantum yields of LPZ in PBS, MeOH and MeCN are 0.13, 0.02 and <10−3, respectively. It is further demonstrated that LPZSO does not form by the reaction of singlet oxygen with ground‐state LPZ. This oxidation product is actually produced by the reaction of the cation radical of LPZ (LPZ·+) with molecular oxygen. This cation radical in turn, is produced by an electron transfer process between the3LPZ* and ground‐state molecular oxygen.