PHOTOPHYSICS AND SKIN PHOTOTOXICITY OF NEUROLEPTIC DRUGS

抗精神病药物或抗精神病药物主要用于治疗。 精神分裂症，但也有应用于躁狂，焦虑，痴呆症 和吸毒。主要使用的抗精神病药属于普通 三环类抗抑郁药(吩噻嗪、二苯并氮卓类和 二苯二氮卓类药物)。这些药物的大多数衍生品也有 产生严重的副作用，包括锥体外系综合征(EPS)， 迟发性运动障碍，帕金森氏症，过敏和光敏化。 衍生品结构的微小变化，改变了模型 药物的作用、效力、光谱和严重程度 副作用。它们的分子光化学机制 光敏能力仍然未知，尽管它们是 实际上在美国用来治疗成千上万的 每年一次的精神科治疗。激光闪光光解有机硅的研究进展 吩噻嗪的一些衍生物表明，它的三重态 氯化吩噻嗪衍生物可被有效地猝灭 溶液中的质子。淬火的效果是非常好的 对药物的结构敏感，似乎与 光毒性。 这个项目的目标是测量一个光物理特性 三环类抗精神病药物的筛选及其短期寿命研究 瞬变的，尤指阳离子自由基和三重态。基本UV-Vis 并将利用发光技术来研究它们的 吸收/发射特性。瞬变的特征将被描述为 使用光学吸收测量与设置的Nd-YAG激光器。为 这些化合物的三重态、消光系数和 量子产额将使用比较法和 三重-三重能量传递原理。组合在一起 MM+/PM3/RHF理论计算将使用HyperCHEM/TM进行 关于整个光物理参数集。试验性的和 理论值将与该化合物的光毒性相关 药物以查明三胞胎瞬变是否直接参与了 该药物家族的光毒活性。这个项目的主要目标是 就是找到一个分子/光物理描述符来描述光毒性的一面 三环类抗精神病药物的疗效。

Anti-psychotic or neuroleptic drugs are used primarily for the treatment of schizophrenia, but also have applications in mania, anxiety, dementia and drug abuse. The major used neuroleptics belong to the general tricyclic anti-depressants family (phenothiazines, dibenzazepines and dibenzodiazepines). Most of the derivatives of these drugs do also produces serious side effects, including extrapyramidal syndrome (EPS), tardative dyskinesia, parkinsonism, allergy and photosensitization. Small changes in the structure of the derivatives, change the model of action of the drugs, the potency and the spectrum and severity of the side effects. The molecular photochemical mechanisms for their photosensitizing ability are still unknown, even though they are actually used in the United States to treat thousands and thousands of psychiatric annually. Recent studies on the laser flash photolysis of some phenothiazine derivatives showed that the triplet state of chlorinated phenothiazine derives can be efficiently quenched by the protons in the solution. The effectiveness of the quenching is very sensitive to the structure of the drug and seems to correlate with the phototoxicity. The goal of this project is to measure the photophysical properties of a selected group of tricyclic neuroleptics and to study their short-lived transients, especially the cation radical and the triplet. Basic UV-VIs and luminescence techniques will be employed to study their absorption/emission properties. The transients will be characterized using optical absorption measurements with a Nd-YAG laser set up. For the triplet state of these compounds, the extinction coefficient and the quantum yield will be determined using a comparative method and the triplet-triplet energy transfer principle, respectively. Combined MM+/PM3/RHF theoretical calculations will be performed with HyperCHEM/TM on the whole set of photophysical parameters. The experimental and theoretical values will be correlated with the phototoxicity of the drugs to find out if the triplet transient is directly involved in the phototoxic activity of this drug family. The major goal of this project is to find a molecular/photophysical descriptor for the phototoxic side effect of tricyclic antipsychotics.