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Effects of ginseng total saponins on the antinociception and the tolerance development of U-50,488H

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Abstract

These studies were performed to investigate the acting sites of ginseng total saponins (GTS) on the U-50,488H-induced antinociception. And the possible mechanisms of the antagonistic effect on the U-50,488H-induced antinociception and the inhibitory effect of the development of tolerance to U-50,488H-induced antinociception by GTS were studied. The U-50,488H-induced antinociception was antagonized in mice pretreated with GTS intraperitoneally, intracerebrally and intrathecally. These antagonisms were reversed by the pretreatment with a serotonin precursor, 5-hydroxytryptophan (5-HTP), but not with a noradrenaline precursor, L-dihydroxyphenylalanine (L-DOPA). However, the intraplantar administration of GTS did not alter the intraplantar U-50,488H-induced antinociception. These findings suggest that U-50,488H-induced antinociception are mediated via the spinal and supraspinal sites. On the other hand, GTS inhibited the development of tolerance to U-50,488H-induced antinociception. The inhibitory effect of GTS on the development of tolerance to U-50,488H-induced antinociception was reversed by pretreatment with 5-HTP, but not with L-DOPA. Therefore, the antagonism of U-50,488H-induced antinociception and the inhibition of the development of tolerance to U-50,488H-induced antinociception by GTS are dependent on serotonergic mechanisms.

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References Cited

  • Bhargava, H. N., Ramarao, P. and Gulati, A. Effects of morphine in rats treated chronically with U-50,488H, a k-opioid receptor agonist.Eur. J. Pharmacol., 162, 257–264 (1989).

    Article  PubMed  CAS  Google Scholar 

  • Basbaum, A. L. and Fields, H. L., Endogenous pain control systems: Brainstem spinal pathways and endorphin circuitry.Ann. Rev. Neurosci., 7, 309–338 (1984).

    Article  PubMed  CAS  Google Scholar 

  • Berge, O. G., Hole, K. and Ogren, S. O., Attenuation of morphine-induced analgesia by p-chlorophenylalanine and p-chloroamphetamine: Test-dependent effects and evidence for brainstem 5-hydroxytryptamine involvement.Brain Res., 271, 51–64 (1983).

    Article  PubMed  CAS  Google Scholar 

  • D’Amour, F. E. and Smith, D. L., A method for determining loss of pain sensation.J. Pharmacol. Exp. Ther., 72, 74–79 (1941).

    Google Scholar 

  • Duart, I. D. G., Lorenzetti, B. B. and Ferreira, S. H., Peripheral analgesia and activation of the nitric oxidecyclic GMP pathway.Eur. J. Pharmacol., 186, 289–291 (1990).

    Article  Google Scholar 

  • Haley, T. J. and McCormick, W. G., Pharmacological effects produced by intracerebral injection of drugs in the conscious mouse.Br. J. Pharmacol., 67, 313–316 (1957).

    Google Scholar 

  • Janice, L. K. H. and Wilcox, G. L., Intrathecal morphine in mice: A new technique.Eur. J. Pharmacol., 12, 12–15 (1980).

    Google Scholar 

  • Kim, H. S., Oh, K. W., Rheu, H. M. and Kim, S. H., Antagonism of U-50,488H-induced antinociception by ginseng total saponin is dependent on serotonergic mechanisms.Pharmacol. Biochem. Behav., 42, 587–593 (1992).

    Article  PubMed  CAS  Google Scholar 

  • Kim, H. S., Jang, C. G. and Lee, M. G., Antinarcotic effects of the standardized ginseng extract G115 on morphine.Planta Medica., 56, 158–163 (1990).

    Article  PubMed  CAS  Google Scholar 

  • Kim, H. S., Oh, K. W. and Oh, S. K., Antagonism of analgesic effect of morphine in mice by ginseng saponins.J. Kor. Pharm. Sci., 16, 135–138 (1986).

    Google Scholar 

  • Lahti, R. A., VonVoitglander, P. F. and Barsuhm, C., Properties of a selective κ-agonist, U-50,488H.Life Sci., 31, 2257–2260 (1982).

    Article  PubMed  CAS  Google Scholar 

  • Millan, M. J., Czlonkowski, A., Lipkowski, A. and Herz, A., Kappa-opioid receptor-mediated antinociception in the rat. II. Supraspinal in addition to spinal sites of action.J. Pharmacol. Exp. Ther., 251, 342–350 (1989).

    PubMed  CAS  Google Scholar 

  • Mark, J. M., κ-Opioid receptors and analgesia.TiPS., 11, 70–76 (1990).

    Google Scholar 

  • Martin, W. R., Eades, C. G., Thompson, J. A., Huppler, R. E. and Gilbert, P. E., The effects of morphine and nalorphine-like drugs in the nondependent and morphine-dependent chronic spinal dog.J. Pharmacol. Exp. Ther., 197, 517–532 (1976).

    PubMed  CAS  Google Scholar 

  • Namba, T., Yoshizaki, T., Tominori, K., Kobashi, K., Mitsui, K. and Hasse, J., Fundamental studies on the evaluation of the crude drugs (1).Planta Medica, 32, 588–602 (1974).

    Google Scholar 

  • Panerai, A. E., Martini, A., Sacerdote, P. and Mantegazza, P., κ-Receptor antagonist reverse ‘non-opioid’ stress-induced analgesia.Brain Res., 304, 153–156 (1984).

    Article  PubMed  CAS  Google Scholar 

  • Petkov, V. W., Effect of ginseng on the brain biogenic monoamines and 3′,5′-AMP system. Arzneim.Forsch./Drug Res., 28, 388–393 (1978).

    CAS  Google Scholar 

  • Roberts, M. H. T., Sizer, A. R. and Rees, H., In Besson, J. M. (Ed),Serotonin and Pain, Elsevier Press, Amsterdam (1990).

    Google Scholar 

  • Stein, C., Millan, N. J., Shippenberg, T. S., Peter, K. and Herz, A., Peripheral opioid receptors mediating antinociception in inflammation: Evidence for involvement of mu, delta and kappa receptors.J. Pharmacol. Exp. Ther., 248, 1269–1275.

  • Taber, R. I. and Latranyi, M. B., Antagonism of the analgesic effects of opioid and non-opioid agents by p-chlorophenylalanine (pCPA).Eur. J. Pharmacol., 75, 215–222 (1981).

    Article  PubMed  CAS  Google Scholar 

  • Takagi, H., Takahashi, T. and Kimura, K., Antagonism of the analgesic effects of morphine in mice by tetrabenazine and reserpine.Arch. Int. Pharmacodyn. Ther., 149, 484–492 (1964).

    PubMed  CAS  Google Scholar 

  • Takagi, H., Inukai, T. and Nakama, M., A modification of Haffner’s method for testing analgesics.Jpn. J. Pharmacol., 16, 287–294 (1966).

    Article  PubMed  CAS  Google Scholar 

  • Takahashi, M., Tokuyama, S. and Kaneto, H., Implication of endogenous opioid mechanism in the production of the antinociceptive effect induced by psychological stress in mice.Jpn. J. Pharmacol., 44, 283–291 (1987).

    Article  PubMed  CAS  Google Scholar 

  • Tenen, S. S., Antagonism of the analgesic effect of morphine and other drugs byp-chlorophenylalanine, a serotonin depletor.Psychopharmacologia, 12, 278–285 (1968).

    Article  PubMed  CAS  Google Scholar 

  • Tyers, M. B., A classification of opiate receptors that mediate antinociception in animals.Br. J. Pharmacol., 69, 503–512 (1980).

    PubMed  CAS  Google Scholar 

  • VonVoitglander, P. F. and Lewis, R. A., U-50,488H, a selective kappa opioid agonist: Comparison to other reputed kappa agonists.Pro. Neur. Psychopharmacol. Biol. Psychiat., 6, 460–467 (1982).

    Google Scholar 

  • VonVoitglander, P. F., Lahti, R. A. and Ludens, J. H., U-50,488H: A selective and structually novel non-mu (kappa) opioid agonist.J. Pharmacol. Exp. Ther., 224, 7–12 (1982).

    Google Scholar 

  • VonVoitglander, P. F., Lewis, R. A. and Neff, G. L., Kappa-opioid analgesia is dependent on serotonergic mechanisms.J. Pharmacol. Exp. Ther., 231, 270–274 (1984).

    Google Scholar 

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Kim, HS., Kim, SH., Seong, YH. et al. Effects of ginseng total saponins on the antinociception and the tolerance development of U-50,488H. Arch. Pharm. Res. 16, 237–243 (1993). https://doi.org/10.1007/BF02974489

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