Tamura K, Mutabagani K, Wood J D
Department of Physiology I, Tokai University School of Medicine, Bohseidai Isehara, Japan.
Eur J Pharmacol. 1993 Mar 2;232(2-3):235-9. doi: 10.1016/0014-2999(93)90779-h.
CP-96,345 [(2S,3S)-cis-2-(diphenylmethyl)-N-[(2-methoxyphenyl)-methyl]- 1-azabicyclo[2.2.2.]octan-3-amine], a novel nonpeptide antagonist of the substance P receptor, was evaluated for blocking action at substance P receptors on myenteric neurons of guinea-pig small intestine. Intracellular electrophysiological recording was used to determine actions of the drug on excitatory responses to substance P, on slow and fast excitatory postsynaptic potentials and action potential initiation and propagation in the neurons. CP-96,345 suppressed responses to substance P. It also suppressed spike initiation and propagation in the neuronal processes, as well as in the somal membranes. The effects of the drug on substance P responses could not be attributed to an action at substance P receptors. The mechanism of action appeared to be a nonselective local anesthetic effect on initiation and propagation of action potentials.
CP - 96,345[（2S，3S）-顺式-2 - （二苯基甲基）-N - [（2 - 甲氧基苯基）甲基]-1 - 氮杂双环[2.2.2]辛烷 - 3 - 胺]，一种新型的P物质受体非肽拮抗剂，被评估其对豚鼠小肠肌间神经元上P物质受体的阻断作用。采用细胞内电生理记录来确定该药物对P物质兴奋性反应、对神经元中慢和快兴奋性突触后电位以及动作电位起始和传播的作用。CP - 96,345抑制了对P物质的反应。它还抑制了神经元突起以及胞体膜中动作电位的起始和传播。该药物对P物质反应的作用不能归因于对P物质受体的作用。其作用机制似乎是对动作电位的起始和传播具有非选择性局部麻醉作用。
