PHOTOPHYSICS AND SKIN PHOTOTOXICITY OF NEUROLEPTIC DRUGS

抗精神病药物或神经安定药物主要用于治疗 精神分裂症，也可以应用于躁狂症，焦虑症， 和药物滥用主要使用的精神抑制剂属于一般 三环类抗抑郁药家族（吩噻嗪、二苯并氮杂卓和 二苯并二氮杂卓）。这些药物的大多数衍生物也 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、帕金森综合征、变态反应和光敏化。 衍生品结构的微小变化， 药物的作用，效力和光谱和严重性， 副作用.分子光化学机制， 光敏化能力仍然是未知的，即使它们是 实际上在美国被用来治疗成千上万的 精神科每年激光闪光光解的研究进展 一些吩噻嗪衍生物表明， 氯代吩噻嗪衍生物可以通过 溶液中的质子。淬火的有效性是非常 对药物的结构敏感，似乎与 光毒性 该项目的目标是测量一个 选择一组三环类神经安定药，并研究其短暂的 瞬变，特别是阳离子自由基和三重态。基本紫外-可见光 和发光技术将被用来研究他们的 吸收/发射特性。瞬变将被表征为 使用具有Nd-YAG激光器设置的光学吸收测量。为 这些化合物的三重态，消光系数和 将使用比较方法确定量子产率， 三重态-三重态能量转移原理。组合 MM +/PM3/RHF理论计算将使用HyperCHEM/TM进行 一整套的地球物理参数。实验和 理论值将与光毒性的 药物，以找出三重瞬变是否直接参与 光毒性活性的药物家族。这个项目的主要目标是 是找到一个光毒性的分子/生物物理描述符 三环类抗精神病药的作用。

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.