Sánchez C, Lembøl H L
H. Lundbeck A/S, Copenhagen, Denmark.
Pharmacol Toxicol. 1994 Jan;74(1):35-9. doi: 10.1111/j.1600-0773.1994.tb01070.x.
The potency of centrally administered non-selective (atropine and N-methyl scopolamine) and putatively selective muscarinic antagonists (pirenzepine, AF-DX 116 and 4-DAMP) in inhibition of oxotremorine-induced hypothermia, tremor and salivation in male mice has been compared with their potency in vitro in three functional systems, where muscarinic effects are mediated preferentially by M1 (i.e. superior cervical ganglion), M2 (i.e. atrium), and M3 (i.e. ileum) receptors. Atropine, N-methyl scopolamine and 4-DAMP potently abolished the effects of oxotremorine. Pirenzepine abolished tremor and salivation, whereas hypothermia was antagonized partially only. AF-DX 116 had but weak antagonistic effects. Atropine and N-methyl scopolamine were potent antagonists in all three in vitro test systems. High potency was also seen with 4-DAMP, in particular in the ileum preparation. Pirenzepine showed its highest potency in the ganglion preparation. AF-DX 116 was a weak and non-selective antagonist in all three in vitro preparations. Our studies indicate that the muscarinic induction of tremor and salivation may be preferentially mediated by M3 receptors whereas both M2 and M3 receptors may be involved in the mediation of hypothermia. However, the overall conclusion is that compounds with higher receptor subtype selectivity are needed.
已将中枢给予的非选择性（阿托品和N - 甲基东莨菪碱）和推定的选择性毒蕈碱拮抗剂（哌仑西平、AF - DX 116和4 - DAMP）对雄性小鼠中氧震颤素诱导的体温过低、震颤和流涎的抑制效力，与其在三个功能系统中的体外效力进行了比较，在这些系统中，毒蕈碱效应优先由M1（即颈上神经节）、M2（即心房）和M3（即回肠）受体介导。阿托品、N - 甲基东莨菪碱和4 - DAMP有效消除了氧震颤素的作用。哌仑西平消除了震颤和流涎，而仅部分拮抗了体温过低。AF - DX 116具有较弱的拮抗作用。阿托品和N - 甲基东莨菪碱在所有三个体外测试系统中都是有效的拮抗剂。4 - DAMP也显示出高效力，特别是在回肠制剂中。哌仑西平在神经节制剂中显示出最高效力。AF - DX 116在所有三种体外制剂中都是一种弱的非选择性拮抗剂。我们的研究表明，震颤和流涎的毒蕈碱诱导可能优先由M3受体介导，而M2和M3受体可能都参与体温过低的介导。然而，总体结论是需要具有更高受体亚型选择性的化合物。
