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mGlu 1受体拮抗剂AIDA(1-氨基茚满-1,5-二羧酸)的抗焦虑样活性

The anxiolytic-like activity of AIDA (1-aminoindan-1,5-dicarboxylic acid), an mGLu 1 receptor antagonist.

作者信息

Kłodzińska A, Tatarczyńska E, Stachowicz K, Chojnacka-Wójcik E

机构信息

Department of New Drugs Research, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.

出版信息

J Physiol Pharmacol. 2004 Mar;55(1 Pt 1):113-26.

Abstract

In the present study we examined the effects of 1-aminoindan-1,5-dicarboxylic acid (AIDA), regarded as a selective and competitive mGluR1 antagonist, in animal models of anxiety. Diazepam (1-10 mg/kg) was used as a reference drug. After intraperitoneal administration, AIDA (0.5-2 mg/kg) produced anxiolytic-like effects in the conflict drinking test and the elevated plus-maze test in rats; however, in doses up to 8 mg/kg, it was inactive in the four-plate test in mice. AIDA tested at the effective doses in the conflict drinking test changed neither the treshold current nor water intake in rats compared to vehicle treatment. AIDA (in a dose of 4 mg/kg, but not lower) increased the exploratory locomotor activity of rats measured in the open-field test, but it did not disturb rat motor coordination in the rota-rod test. The above results indicate that selective mGluR1 antagonist AIDA induces antianxiety-like effects at a low risk of acute side effects characteristic of benzodiazepines. Further studies are required to identify the sites and the mechanism of action of AIDA.

摘要

在本研究中,我们研究了被视为选择性竞争性代谢型谷氨酸受体1(mGluR1)拮抗剂的1-氨基茚满-1,5-二羧酸(AIDA)在焦虑动物模型中的作用。地西泮(1 - 10毫克/千克)用作参比药物。腹腔注射后,AIDA(0.5 - 2毫克/千克)在大鼠的冲突饮水试验和高架十字迷宫试验中产生了抗焦虑样作用;然而,在高达8毫克/千克的剂量下,它在小鼠的四板试验中无活性。在冲突饮水试验中以有效剂量测试的AIDA与溶剂处理相比,既未改变大鼠的阈电流,也未改变其饮水量。AIDA(4毫克/千克的剂量,但不是更低剂量)增加了在旷场试验中测量的大鼠的探索性运动活动,但在转棒试验中未干扰大鼠的运动协调性。上述结果表明,选择性mGluR1拮抗剂AIDA诱导抗焦虑样作用,且具有苯二氮䓬类药物典型急性副作用的低风险。需要进一步研究以确定AIDA的作用部位和作用机制。

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