Vereczkey L
Central Research Institute for Chemistry, Hungarian Academy of Sciences, Budapest.
Acta Physiol Hung. 1995;83(1):47-50.
One of the basic principles of the modern pharmacological research is that there is a close correlation between the chemical structure and the pharmacological effect. In contrast to pharmacology, in toxicology high doses of the drugs are used in order to provoke toxic symptoms generally realized through other receptors than the pharmacological effect. The evaluation of the structure activity relationship (SAR) in toxicology is hindered by the fact that it is not possible to establish in every case that the toxic effect 1. is developed by the original compound or its metabolite(s) 2. is realized through one or more receptors. Furthermore it is necessary to take into consideration that the studies in toxicology are not carried out with so many compounds as the studies in pharmacology and--horrible dictu--the toxicological data are not always public. Thus the prediction of the toxicity of a compound on the base of its chemical structure is difficult, and the prediction whether a new drug is toxic to such an extent that excludes its development, is impossible. What we can do is trying to predict--in the knowledge of the metabolism of the drug--its possible carcinogenic, hepatotoxic, CNS etc. toxic effect.
现代药理学研究的基本原则之一是化学结构与药理作用之间存在密切关联。与药理学不同，毒理学中使用高剂量药物以引发毒性症状，这些症状通常通过与药理作用不同的其他受体来实现。毒理学中结构活性关系（SAR）的评估受到以下事实的阻碍：在每种情况下都不可能确定毒性作用1. 是由原始化合物或其代谢物产生的，2. 是通过一个或多个受体实现的。此外，有必要考虑到毒理学研究中使用的化合物数量不如药理学研究中的多，而且——可怕的是——毒理学数据并不总是公开的。因此，基于化合物的化学结构预测其毒性很困难，而预测一种新药是否具有足以排除其开发的毒性则是不可能的。我们所能做的是在了解药物代谢的基础上，尝试预测其可能的致癌、肝毒性、对中枢神经系统等的毒性作用。
