利用大鼠离体肛尾肌评估拮抗剂的效能

On the assessment of the potency of antagonists using the rat isolated anococcygeus muscle.

作者信息

Doggrell S A

出版信息

J Pharmacol Methods. 1983 Dec;10(4):243-54. doi: 10.1016/0160-5402(83)90018-9.

Abstract

The conditions required for assessing the potencies of antagonists of muscarinic and at alpha-adrenoceptors have been examined using contractility studies with the rat anococcygeus muscle. Physostigmine (5 X 10(-7) M) and atropine (10(-8)-10(-7) M) had no effect on the responses to noradrenaline. The responses to acetylcholine were potentiated by physostigmine and inhibited by atropine. Physostigmine and atropine increased the slopes of the concentration-response curves to acetylcholine. In the presence of physostigmine, atropine at 10(-8) M inhibited the responses without altering the slopes of the concentration-response curves to acetylcholine. The responses to acetylcholine were potentiated by cocaine (greater than 10(-6) M) and inhibited by phentolamine (10(-6) M). Cocaine (10(-6) - 5 X 10(-6) M) potentiated and phentolamine (10(-7) - 10(-6) M) inhibited the responses to noradrenaline. The slopes of the concentration-response curves to noradrenaline were increased by cocaine at 5 X 10(-6) M, but not at 10(-6) - 2 X 10(-6) M, and by phentolamine. In the presence of cocaine (10(-6) M), phentolamine (10(-7) - 5 X 10(-7) M) inhibited the responses and increased the slopes of the concentration-response curves to noradrenaline. These results illustrate that, in the rat anococcygeus muscle, it is possible to assess the potency of muscarinic antagonists with the method described. However, in this tissue, alpha-adrenoceptor blocking activity cannot be determined with noradrenaline as the agonist in the presence of cocaine.

摘要

采用大鼠肛尾肌收缩性研究方法，对评估毒蕈碱拮抗剂和α-肾上腺素能受体拮抗剂效能所需的条件进行了研究。毒扁豆碱（5×10⁻⁷ M）和阿托品（10⁻⁸ - 10⁻⁷ M）对去甲肾上腺素的反应无影响。毒扁豆碱增强了对乙酰胆碱的反应，而阿托品则抑制了该反应。毒扁豆碱和阿托品增加了乙酰胆碱浓度-反应曲线的斜率。在毒扁豆碱存在的情况下，10⁻⁸ M的阿托品抑制了反应，但未改变乙酰胆碱浓度-反应曲线的斜率。可卡因（大于10⁻⁶ M）增强了对乙酰胆碱的反应，酚妥拉明（10⁻⁶ M）则抑制了该反应。可卡因（10⁻⁶ - 5×10⁻⁶ M）增强了对去甲肾上腺素的反应，酚妥拉明（10⁻⁷ - 10⁻⁶ M）则抑制了该反应。5×10⁻⁶ M的可卡因增加了去甲肾上腺素浓度-反应曲线的斜率，但10⁻⁶ - 2×10⁻⁶ M的可卡因未增加该斜率，酚妥拉明也增加了该斜率。在可卡因（10⁻⁶ M）存在的情况下，酚妥拉明（10⁻⁷ - 5×10⁻⁷ M）抑制了反应并增加了去甲肾上腺素浓度-反应曲线的斜率。这些结果表明，在大鼠肛尾肌中，采用所述方法可以评估毒蕈碱拮抗剂的效能。然而，在该组织中，当存在可卡因时，以去甲肾上腺素为激动剂无法确定α-肾上腺素能受体阻断活性。