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Pharmacological characterisation of NK1 receptor antagonist, [D-Trp7]sendide, on behaviour elicited by substance P in the mouse

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Abstract

An analogue of sendide, [DTrp7]sendide, was newly synthetized and evaluated as a putative NK1 receptor antagonist in a mouse behavioural test. Effects of [DTrp7]sendide on the scratching, biting and licking response induced by substance P (SP), neurokinin A (NK A) and neurokinin B (NK B) was studied after intrathecal injections. When administered simultaneously with SP, an endogenous agonist for NK1 receptors, [DTrp7]sendide inhibited the behavioural response to this tachykinin in a dose-dependent manner with ID50 value of 1 t.0 pmol/mouse. The behavioural response elicited by other NK1 receptor agonists, septide and physalaemin, was reduced significantly by a small dose (32.0 pmol) of [DTrp7]sendide. Large doses (nmol order) of [DTrp7]sendide were needed to reduce the characteristic behaviour of NK A, an NK2 agonist, NK B, an NK3 agonist and eledoisin, an NK2/NK3 agonist. The duration of the antagonistic effect of [DTrp7]sendide was relatively longer. In a [3H]labeled SP binding assay using mouse spinal cord membranes, [DTrp7]sendide potently displaced [3H] labeled SP binding with a Ki value of 0.023 ± 0.007 nM, which was approximately 140 and 9400 times more potent than that of unlabeled SP and CP-96,345, respectively. These findings suggest that [DTrp7]sendide interacts selectively with the NK1 receptor in the mouse spinal cord as assayed by the receptor binding and SP-induced behavioural tests.

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Authors and Affiliations

  1. Department of Pharmacology, Tohoku College of Pharmacy, 4-4-1 Komatsushima, 981, Aoba-ku, Sendai, Japan

    T. Sakurada, H. Yogo, Y. Manome, K. Tan-No, S. Sakurada, A. Yamada & K. Kisara

  2. Production, Research and Development Division, Asahi Glass Co., LTD, 221, Hazawa, Yokohama, Japan

    M. Ohba

Authors
  1. T. Sakurada
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  2. H. Yogo
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  3. Y. Manome
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  4. K. Tan-No
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  5. S. Sakurada
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  6. A. Yamada
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  7. K. Kisara
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  8. M. Ohba
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Correspondence to: T. Sakurada at the above address

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Sakurada, T., Yogo, H., Manome, Y. et al. Pharmacological characterisation of NK1 receptor antagonist, [D-Trp7]sendide, on behaviour elicited by substance P in the mouse. Naunyn-Schmiedeberg's Arch Pharmacol 350, 387–392 (1994). https://doi.org/10.1007/BF00178956

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  • DOI: https://doi.org/10.1007/BF00178956

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