Fernández Sebastián P, Wasowski Cristina, Paladini Alejandro C, Marder Mariel
Instituto de Química y Fisicoquímica Biológicas, Facultad de Farmacia y Bioquímica, Junín 956 (C1113AAD), Buenos Aires, Argentina.
Eur J Pharmacol. 2005 Apr 11;512(2-3):189-98. doi: 10.1016/j.ejphar.2005.02.039.
It has been recently reported the presence in Valeriana of the flavone 6-methylapigenin and the flavanone glycoside hesperidin. The apigenin derivative is a ligand for the benzodiazepine binding site in the gamma-aminobutyric acid receptor type A (GABA(A)) and has anxiolytic properties. Hesperidin has sedative and sleep-enhancing properties but is not a ligand for the benzodiazepine binding site. 6-Methylapigenin is able to potentiate the sleep-enhancing effect of hesperidin. In this work we demonstrate that this property is shared with various GABA(A) receptor ligands, among them the agonist diazepam, which was used to study the potentiation as measured in the hole board test. Isobolar analysis of the results showed the interaction being synergistic. We discarded pharmacokinetic effects or a direct action of hesperidin on the benzodiazepine binding site. A possible use of hesperidin properties to decrease the effective therapeutic doses of benzodiazepines is suggested.
最近有报道称缬草中存在黄酮类化合物6-甲基芹菜素和黄烷酮糖苷橙皮苷。芹菜素衍生物是A型γ-氨基丁酸受体（GABA(A)）中苯二氮䓬结合位点的配体，具有抗焦虑特性。橙皮苷具有镇静和增强睡眠的特性，但不是苯二氮䓬结合位点的配体。6-甲基芹菜素能够增强橙皮苷的促睡眠作用。在这项研究中，我们证明这种特性与多种GABA(A)受体配体相同，其中包括激动剂地西泮，它被用于研究在洞板试验中测量的增强作用。对结果的等效线分析表明这种相互作用是协同的。我们排除了药代动力学效应或橙皮苷对苯二氮䓬结合位点的直接作用。有人提出可以利用橙皮苷的特性来降低苯二氮䓬类药物的有效治疗剂量。
