Sakurada T, Manome Y, Katsumata K, Tan-No K, Sakurada S, Ohba M, Kisara K
Department of Pharmacology, Tohoku College of Pharmacy, Sendai, Japan.
Eur J Pharmacol. 1994 Aug 11;261(1-2):85-90. doi: 10.1016/0014-2999(94)90304-2.
Intrathecal administration of the tachykinin NK1 receptor agonists, substance P, physalaemin, septide and [Sar9, Met(O2)11]substance P, elicited a characteristic behavioural response consisting of scratching, biting and licking in mice. The behavioural response induced by substance P was significantly inhibited by simultaneous intrathecal injection of a tachykinin NK1 receptor antagonist, [Tyr6,D-Phe7,D-His9]substance P-(6-11) (sendide), and a non-peptide antagonist, (2S,3S)-cis-2-(di-phenylmethyl)-N-[(2- methoxyphenyl)-methyl]-1-azabicyclo[2.2.2]octan-3-amine. The duration of the antagonistic effect of sendide was similar to that of CP-96,345. The antagonistic effect of sendide on the response induced by tachykinin NK1 receptor agonists was approximately 1000 times more potent than that of CP-96,345. Neither antagonist inhibited neurokinin A-, D-septide-, neurokinin B- and eledoisin-induced scratching, biting and licking responses. Sendide was without effect on motor performance as measured by the rotarod test, while motor incoordination was elicited only 2 min after intrathecal injection of CP-96,345. These results indicate that sendide and CP-96,345 are selective antagonists of tachykinin NK1 receptors with a long duration of action.
在小鼠中，鞘内注射速激肽NK1受体激动剂P物质、雨蛙肽、八肽及[Sar9, Met(O2)11]P物质，可引发由抓挠、啃咬和舔舐组成的特征性行为反应。同时鞘内注射速激肽NK1受体拮抗剂[酪氨酸6，D-苯丙氨酸7，D-组氨酸9]P物质-(6-11)（仙台肽）和非肽拮抗剂(2S,3S)-顺式-2-(二苯甲基)-N-[(2-甲氧基苯基)-甲基]-1-氮杂双环[2.2.2]辛烷-3-胺，可显著抑制P物质诱导的行为反应。仙台肽的拮抗作用持续时间与CP-96,345相似。仙台肽对速激肽NK1受体激动剂诱导反应的拮抗作用比CP-96,345强约1000倍。两种拮抗剂均未抑制神经激肽A、D-肽、神经激肽B和蛙皮素诱导的抓挠、啃咬和舔舐反应。通过转棒试验测定，仙台肽对运动性能无影响，而鞘内注射CP-96,345后仅2分钟就引发了运动不协调。这些结果表明，仙台肽和CP-96,345是速激肽NK1受体的选择性拮抗剂，作用持续时间长。
