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Research ArticleNEUROPHARMACOLOGY

Assessment of Mechanisms Involved in Antinociception Caused by Sesquiterpene Polygodial

Gilboé L. Mendes, Adair R. S. Santos, Angela Malheiros, Valdir Cechinel Filho, Rosendo A. Yunes and João B. Calixto
Journal of Pharmacology and Experimental Therapeutics January 2000, 292 (1) 164-172;
Gilboé L. Mendes
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Adair R. S. Santos
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Angela Malheiros
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Valdir Cechinel Filho
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Rosendo A. Yunes
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João B. Calixto
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Abstract

Polygodial, a sesquiterpene isolated from the bark ofDrymis winteri given systemically, intraplantarly, or by spinal or supraspinal sites, produced antinociception when assessed in both phases of the formalin test and against capsaicin-induced pain. Polygodial, even at high doses, had no antinociceptive or antihyperalgesic effect when assessed in hot-plate assay or in glutamate-induced hyperalgesia, nor did it significantly interfere with the motor coordination of animals when tested in the rota-rod test. The polygodial antinociception assessed in the formalin test was not affected by i.p. treatment of animals with cyprodime, yohimbine, phaclofen, bicuculine, or nitric oxide precursor or by intrathecal administration of potassium channel blockers such as apamin, charybdotoxin, glibenclamide, or tetraethylammonium. In contrast, polygodial antinociception was significantly attenuated by i.p. treatment of animals with naloxone, naltrindole, 2-(3,4-dichlorophenyl)-n-methyl-n-[(1S)-1-(3-isothiocynatophenyl)-2-(1-pryrolidinyl)ethyl]acetamide,p-chlorophenylalanine, prazosin, or by i.c.v. treatment with pertussis toxin. In addition, polygodial antinociception was not cross-tolerant to morphine, nor was its effect affected by the adrenalectomy of animals. Together, these results show that polygodial produces pronounced systemic, spinal, and supraspinal antinociception in mice, mainly preventing the neurogenic pain produced by formalin and capsaicin. The mechanism by which polygodial produces antinociception seems likely to involve an interaction with the opioid system, mainly κ and δ subtypes, depend on the activation of Gi/o protein sensitive to pertussis toxin, α1-adrenoceptors, and the serotoninergic system. Collectively, these results suggest that polygodial itself or its derivatives may have potential therapeutic value for the development of new analgesic drugs.

Footnotes

  • Send reprint requests to: João B. Calixto, Department of Pharmacology, CCB, Universidade Federal de Santa Catarina, Rua Ferreira Lima, 82, 88015-420, Florianópolis SC, Brazil. E-mail:calixto{at}farmaco.ufsc.br

  • ↵1 This work was supported by grants from Conselho Nacional de Desenvolvimento Cientı́fico e Tecnológico and Financiadora de Estudos e Projetos, Brazil.

  • Abbreviations:
    i.t.
    intrathecal
    DIPPA
    2-(3,4-dichlorophenyl)-n-methyl-n-[(1S)-1-(3-isothiocynatophenyl)-2-(1-pryrolidinyl)ethyl]acetamide
    TEA
    tetraethylammonium
    PCPA
    d,l-p-chlorophenylalanine methyl ester hydrochloride
    l-NOARG
    NG-nitro-l-arginine
    GABA
    γ-aminobutyric acid
    SHO
    sham-operated
    • Received June 15, 1999.
    • Accepted September 13, 1999.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 292 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 292, Issue 1
1 Jan 2000
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Research ArticleNEUROPHARMACOLOGY

Assessment of Mechanisms Involved in Antinociception Caused by Sesquiterpene Polygodial

Gilboé L. Mendes, Adair R. S. Santos, Angela Malheiros, Valdir Cechinel Filho, Rosendo A. Yunes and João B. Calixto
Journal of Pharmacology and Experimental Therapeutics January 1, 2000, 292 (1) 164-172;

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Research ArticleNEUROPHARMACOLOGY

Assessment of Mechanisms Involved in Antinociception Caused by Sesquiterpene Polygodial

Gilboé L. Mendes, Adair R. S. Santos, Angela Malheiros, Valdir Cechinel Filho, Rosendo A. Yunes and João B. Calixto
Journal of Pharmacology and Experimental Therapeutics January 1, 2000, 292 (1) 164-172;
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