Barnes J C, Roberts F F
Department of Neuropharmacology, Glaxo Group Research Ltd., Ware, Hertfordshire, U.K.
Eur J Pharmacol. 1991 Mar 26;195(2):233-40. doi: 10.1016/0014-2999(91)90540-7.
The in vivo central effects of a range of full and partial muscarinic receptor agonists have been investigated on hippocampal theta rhythm and blood pressure. In the isoflurane-anaesthetised rat, pretreated with N-methylscopolamine, i.v. administration of arecoline, oxotremorine, arecaidine propargyl ester, aceclidine and pilocarpine produced dose-dependent increases in the frequency of hippocampal theta rhythm and blood pressure, with an order of potency of arecoline = oxotremorine = arecaidine propargyl ester greater than aceclidine greater than or equal to pilocarpine. To increase theta wave frequency, pilocarpine showed a low maximum response and possessed antagonist activity against arecoline, indicating that pilocarpine was acting as a partial agonist. AF102B failed to alter blood pressure or theta rhythm. Intraventricular injections of scopolamine and the M1 receptor-selective antagonist, pirenzepine, produced dose-dependent antagonism of the enhanced theta wave frequency and hypertensive response produced by arecoline. The differences in antagonist potency for the two responses was less than 6-fold, which indicated that both the increase in hippocampal theta wave activity and increase in blood pressure may have been mediated through muscarinic receptors of the M1 subtype. Further studies using a wider range of antagonists will be required to confirm this conclusion.
一系列完全和部分毒蕈碱受体激动剂对海马θ节律和血压的体内中枢效应已被研究。在经N - 甲基东莨菪碱预处理的异氟烷麻醉大鼠中，静脉注射槟榔碱、氧化震颤素、槟榔次碱炔丙酯、醋克利定和毛果芸香碱可使海马θ节律频率和血压呈剂量依赖性增加，其效力顺序为槟榔碱 = 氧化震颤素 = 槟榔次碱炔丙酯大于醋克利定大于或等于毛果芸香碱。为增加θ波频率，毛果芸香碱显示出较低的最大反应，并对槟榔碱具有拮抗活性，表明毛果芸香碱作为部分激动剂起作用。AF102B未能改变血压或θ节律。脑室内注射东莨菪碱和M1受体选择性拮抗剂哌仑西平，可对槟榔碱产生的增强的θ波频率和高血压反应产生剂量依赖性拮抗作用。两种反应的拮抗剂效力差异小于6倍，这表明海马θ波活动增加和血压升高可能均通过M1亚型毒蕈碱受体介导。需要使用更广泛的拮抗剂进行进一步研究以证实这一结论。
