Potent antinociceptive effects of TRK-820, a novel κ-opioid receptor agonist

Takashi Endoh, Hirotoshi Matsuura, Atsushi Tajima, Naoki Izumimoto, Chiko Tajima, Tomohiko Suzuki, Akiyoshi Saitoh, Tsutomu Suzuki, Minoru Narita, Leon Tseng, Hiroshi Nagase

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Abstract

TRK-820, a new type of 4,5-epoxymorphinan derivative, was investigated in vivo for antinociceptive activities and its selectivity on various opioid receptors in mice. TRK-820 given s.c. or p.o. was found to be 351- and 796-fold more potent than U50,488H with acetic acid-induced abdominal constriction test. The duration of the antinociceptive effect produced by TRK-820 was longer than that produced by μ-opioid receptor agonist morphine or other κ-opioid receptor agonists. In addition, with four other antinociceptive assays, low temperature hot plate (51 °C), thermal tail flick, mechanical tail pressure and tail pinch tests, TRK-820 was also found to be 68- to 328-fold more potent than U-50488H, and 41- to 349-fold more potent than morphine in producing antinociception, as comparing the weight of the different compound. However, TRK-820 was less active in inhibiting the high temperature (55°C) hot plate response. The antinociceptive effects produced by TRK-820 were inhibited by nor-BNI, but not by naloxone or naltrindole (NTI) with the abdominal constriction test, indicating that the antinociception is selectively mediated by the stimulation of κ-, but not μ- or δ-opioid receptors. Co-administration of TRK-820 with morphine slightly enhanced the antinociception induced by morphine in the mouse hot plate test. On the other hand, pentazocine significantly reduced the morphine-induced antinociception. TRK-820 produced sedation at doses, which are much higher than the doses for producing antinociception. These results indicate that the potent antinociception induced by TRK-820 is mediated via the stimulation of κ-, but not μ- or δ-opiod receptors.

Original languageEnglish
Pages (from-to)1685-1694
Number of pages10
JournalLife Sciences
Volume65
Issue number16
DOIs
Publication statusPublished - 10 Sep 1999

Keywords

  • κ Agonist
  • Antinociception
  • Opioid receptor
  • TRK-820

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    Endoh, T., Matsuura, H., Tajima, A., Izumimoto, N., Tajima, C., Suzuki, T., Saitoh, A., Suzuki, T., Narita, M., Tseng, L., & Nagase, H. (1999). Potent antinociceptive effects of TRK-820, a novel κ-opioid receptor agonist. Life Sciences, 65(16), 1685-1694. https://doi.org/10.1016/S0024-3205(99)00417-8