Ong J, Kerr D I, Ansar M, Vaccher C, Berthelot P
Department of Anaesthesia and Intensive Care, The University of Adelaide, South Australia, Australia.
Can J Physiol Pharmacol. 1998 Jul-Aug;76(7-8):798-801. doi: 10.1139/cjpp-76-7-8-798.
(R,S)-4-Amino-3-(7-methylbenzo[b]furan-2-yl)-butanoic acid (7-MBFG), a new benzofuran analogue of the GABA(B) receptor agonist baclofen, has been evaluated for pharmacological activity on GABA(B) receptors in the guinea-pig isolated ileum and rat neocortical slices. 7-MBFG (300 and 500 microM) reversibly antagonized the (R,S)-baclofen induced depression of cholinergic twitch contractions in the guinea-pig ileum and shifted the concentration-response curve for baclofen to the right, in a parallel manner, giving an apparent pA2 value of 3.7+/-0.3. Likewise, 7-MBFG (300 and 500 microM) reversibly blocked the baclofen-induced suppression of spontaneous discharges, in rat neocortical slices maintained in Mg2+ -free Krebs medium, and caused a rightward, parallel shift of the baclofen concentration-response curve, giving an apparent pA2 value of 4.1+/-0.1. The compound 7-MBFG belongs to a novel, new class of antagonist at central and peripheral GABA(B) receptors, in which the antagonist properties reside in the pseudo-aromatic character of their 3-benzo[b]furan-2-yl substituents, and might provide useful leads for further development of GABA(B) receptor ligands.
（R，S）-4-氨基-3-（7-甲基苯并[b]呋喃-2-基）丁酸（7-MBFG）是γ-氨基丁酸B（GABA(B)）受体激动剂巴氯芬的一种新型苯并呋喃类似物，已在豚鼠离体回肠和大鼠新皮质切片中对其GABA(B)受体的药理活性进行了评估。7-MBFG（300和500微摩尔）可逆性拮抗（R，S）-巴氯芬诱导的豚鼠回肠胆碱能抽搐收缩抑制，并使巴氯芬的浓度-反应曲线平行右移，表观pA2值为3.7±0.3。同样，在无镁的Krebs培养基中培养的大鼠新皮质切片中，7-MBFG（300和500微摩尔）可逆性阻断巴氯芬诱导的自发放电抑制，并使巴氯芬浓度-反应曲线平行右移，表观pA2值为4.1±0.1。化合物7-MBFG属于一类新型的中枢和外周GABA(B)受体拮抗剂，其拮抗特性存在于其3-苯并[b]呋喃-2-基取代基的准芳香性质中，可能为进一步开发GABA(B)受体配体提供有用的线索。
