Vrolijk Misha F, Opperhuizen Antoon, Jansen Eugène H J M, Bast Aalt, Haenen Guido R M M
Department of Pharmacology and Toxicology, Maastricht University, Maastricht, the Netherlands.
Netherlands Food and Consumer Product Safety Authority (NVWA), Utrecht, the Netherlands.
Basic Clin Pharmacol Toxicol. 2015 Dec;117(6):427-32. doi: 10.1111/bcpt.12437. Epub 2015 Jul 24.
Many compounds display anticholinergic effects which might give rise to cognitive impairment and even delirium. These side effects are caused by their ability to bind to muscarinic receptors in our brain. Especially with combination of compounds, these serious effects are seen. This phenomenon, known as anticholinergic accumulation, is especially seen in the elderly. A classification of drugs for anticholinergic side effects has been made based on clinical observations, the ACB score. Here, we aimed to substantiate this classification by comparing the affinity of numerous drugs for the muscarinic receptors to the ACB score. Additionally, a number of supplements were screened. The affinity of the compounds was determined by their ability to displace the radioligand [(3)H]pirenzepine of the muscarinic receptor induced by these compounds. Our results show that the affinity of a compound for the muscarinic receptors correlated with its ACB score. Also food supplements appeared to bind to these muscarinic receptors. Moreover, several drug-drug, supplement-supplement and supplement-drug combinations had an affinity that is higher than the affinity of single compounds. This explains the phenomenon of anticholinergic accumulation. In conclusion, care should be taken to drug-drug and supplement-drug combinations with respect to anticholinergic accumulation.
许多化合物具有抗胆碱能作用，这可能导致认知障碍甚至谵妄。这些副作用是由于它们能够与我们大脑中的毒蕈碱受体结合。特别是在化合物联合使用时，会出现这些严重影响。这种现象，即抗胆碱能蓄积，在老年人中尤为常见。基于临床观察制定了抗胆碱能副作用药物分类，即ACB评分。在此，我们旨在通过比较多种药物对毒蕈碱受体的亲和力与ACB评分来证实这一分类。此外，还对一些补充剂进行了筛选。化合物的亲和力通过其取代由这些化合物诱导的毒蕈碱受体放射性配体[(3)H]哌仑西平的能力来确定。我们的结果表明，化合物对毒蕈碱受体的亲和力与其ACB评分相关。食品补充剂似乎也能与这些毒蕈碱受体结合。此外，几种药物-药物、补充剂-补充剂和补充剂-药物组合的亲和力高于单一化合物的亲和力。这解释了抗胆碱能蓄积现象。总之，对于抗胆碱能蓄积，应注意药物-药物和补充剂-药物组合。
