Barocelli E, Ballabeni V, Chiavarini M, Molina E, Lavezzo A, Impicciatore M
Institute of Pharmacology and Pharmacognosy, University of Parma, Italy.
Eur J Pharmacol. 1994 Mar 11;254(1-2):151-7. doi: 10.1016/0014-2999(94)90382-4.
The new pirenzepine analogue DF 545 has been tested for its muscarinic M1 and M3 receptor antagonist properties in guinea-pig longitudinal muscle-myenteric plexus preparations. McN-A-343-induced inhibition of twitch contractions was taken as a parameter for muscarinic M1 receptor activation while electrical and acetylcholine-induced contractions were considered as a model for muscarinic M3 receptor stimulation. An unexpected contractile effect evoked by McN-A-343 was also investigated. In contrast to pirenzepine, DF 545 only weakly counteracted the M1-mediated McN-A-343 inhibitory effect but blocked M3-related twitch- or acetylcholine-stimulated responses with a 2-fold higher affinity than pirenzepine. Therefore, in this preparation, our findings suggest that DF 545 does not share the selectivity profile exhibited by pirenzepine at ileal muscarinic receptors. Studies on the McN-A-343 contractile effect provide evidence that this agonist may interact with ileal muscarinic effector sites in a different way from other cholinergic agents.
新型哌仑西平类似物DF 545已在豚鼠纵行肌-肠肌丛制备物中进行了毒蕈碱M1和M3受体拮抗剂特性测试。以McN-A-343诱导的抽搐收缩抑制作为毒蕈碱M1受体激活的参数，而电刺激和乙酰胆碱诱导的收缩则被视为毒蕈碱M3受体刺激的模型。还研究了McN-A-343引起的意外收缩效应。与哌仑西平不同，DF 545仅微弱地对抗M1介导的McN-A-343抑制作用，但以比哌仑西平高2倍的亲和力阻断M3相关的抽搐或乙酰胆碱刺激的反应。因此，在该制备物中，我们的研究结果表明DF 545不具有哌仑西平在回肠毒蕈碱受体上表现出的选择性特征。对McN-A-343收缩效应的研究提供了证据，表明该激动剂可能以与其他胆碱能药物不同的方式与回肠毒蕈碱效应位点相互作用。
