PHOTOPHYSICS AND SKIN PHOTOTOXICITY OF NEUROLEPTIC DRUGS

神经安定药物的光物理学和皮肤光毒性

• 批准号: 6437019
• 负责人: CARMELO GARCIA-RUIZ
• 金额: $ 25.93万
• 依托单位: UNIVERSITY OF PUERTO RICO AT HUMACAO
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-04-01 至 2002-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6437019
• 关键词: antipsychotic agents; atomic absorption spectrometry; cations; chemical structure function; chlorpromazine; clozapine; computer program /software; cytotoxicity; drug adverse effect; drug design /synthesis /production; flash photolysis; imipramine; infrared spectrometry; lasers; mass spectrometry; mathematical model; nuclear magnetic resonance spectroscopy; photochemistry; promazine; triplet state; ultraviolet spectrometry

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.

抗精神病或神经肌肉药物主要用于治疗 精神分裂症，但在躁狂症，焦虑，痴呆症中也有应用 和吸毒。主要使用的神经疗法属于一般 三环抗抑制剂家族（苯噻嗪，二苯唑啉和 Dibenzodiazepines）。这些药物的大多数衍生物也确实 产生严重的副作用，包括锥体外综合征（EPS）， 迟钝的运动障碍，帕金森氏症，过敏和光敏化。 衍生物结构的小变化，改变 药物的作用，效力和频谱和严重程度 副作用。其分子光化学机制 即使它们是光敏能力，即使它们是 实际上在美国用来治疗成千上万 每年精神病。关于激光闪光光解的最新研究 一些势噻嗪衍生物表明三胞胎的状态 氯化苯噻嗪衍生的衍生 溶液中的质子。淬火的有效性非常 对药物的结构敏感，似乎与 光毒性。 该项目的目的是测量A的光物理特性 选定的三环神经疗法，并研究其短暂的 瞬态，尤其是阳离子自由基和三胞胎。基本的UV-VIS 并将采用发光技术来研究他们的 吸收/排放特性。瞬态将被描述 使用ND-YAG激光器设置的光吸收测量值。为了 这些化合物的三胞胎状态，灭绝系数和 量子收率将使用比较方法确定 三胞胎 - 三曲线能量转移原理。合并 MM+/PM3/RHF理论计算将使用HyperChem/TM进行 在整个光物理参数上。实验和 理论价值将与该理论值与光毒性相关 吸毒以找出三胞胎瞬态是否直接参与 该药物家族的光毒活性。该项目的主要目标 是为光毒侧找到分子/光物理描述符 三环抗精神病药的作用。