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首页> 外文期刊>Neurochemistry International: The International Journal for the Rapid Publication of Critical Reviews, Preliminary and Original Research Communications in Neurochemistry >Allosteric modulation of (3H)EBOB binding to GABAA receptors by diflunisal analogues.
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Allosteric modulation of (3H)EBOB binding to GABAA receptors by diflunisal analogues.

机译：（3H）EBOB通过二氟菊酯类似物的变构调节。

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摘要

Allosteric modulatory effects of 12 biphenyl derivatives of diflunisal and two fenamates were studied on A-type receptors of GABA (GABAAR) via [3H]4'-ethynylbicycloorthobenzoate (EBOB) binding to synaptic membrane preparations of rat forebrain. A simplified ternary allosteric model was used to determine binding affinities of the compounds and the extents of cooperativity with GABA. Structure activity analysis revealed that 4-hydroxy substituents of the biphenyls contribute to their micromolar binding affinities more than 3-carboxyl groups. Electron-withdrawing fluorinated substituents, especially in ortho position, were also advantageous. These factors also strongly enhanced the cooperativity with GABA binding. The correlation between displacing potency of the allosteric agents and cooperativity with GABA suggests that these processes are associated with common mechanisms. The pharmacological relevance of these interactions is discussed. These data help to differentiate the structural requirements of these agents to act on GABAergic neurotransmission versus nonsteroidal anti-inflammatory effects.
机译：通过[3H] 4'-乙炔基双环原苯甲酸酯（EBOB）与大鼠前脑突触膜制剂的结合，研究了二氟菊酯和两种犬酸酯的12个联苯衍生物和两种犬酸酯的变构调节作用。使用简化的三元变构模型来确定化合物的结合亲和力和与GABA的协同作用程度。结构活性分析表明，联苯的4-羟基取代基比3-羧基更有助于它们的微摩尔结合亲和力。吸电子的氟化取代基，特别是在邻位的氟化取代基也是有利的。这些因素还强烈增强了与GABA结合的协同作用。变构剂的取代效力与与GABA的协同作用之间的相关性表明，这些过程与常见机制相关。讨论了这些相互作用的药理学意义。这些数据有助于区分这些药物对GABA能神经传递与非甾体抗炎作用的结构要求。

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