PT  - JOURNAL ARTICLE
AU  - Gilboé L. Mendes
AU  - Adair R. S. Santos
AU  - Angela Malheiros
AU  - Valdir Cechinel Filho
AU  - Rosendo A. Yunes
AU  - João B. Calixto
TI  - Assessment of Mechanisms Involved in Antinociception Caused by Sesquiterpene Polygodial
DP  - 2000 Jan 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 164--172
VI  - 292
IP  - 1
4099  - http://jpet.aspetjournals.org/content/292/1/164.short
4100  - http://jpet.aspetjournals.org/content/292/1/164.full
SO  - J Pharmacol Exp Ther2000 Jan 01; 292
AB  - 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. The American Society for Pharmacology and Experimental Therapeutics