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Geranylgeraniol and 6α,7β-dihydroxyvouacapan-17β-oate methyl ester isolated from Pterodon pubescens Benth.: Further investigation on the antinociceptive mechanisms of action.

Abstract
The crude alcoholic extracts obtained from Pterodon pubescens Benth. seeds are widely used in Brazilian folk medicine as anti-inflammatory, analgesic, anti-rheumatic tonics and depurative preparations. We previously demonstrated the antinociceptive activity on writhing capsaicin, glutamate, and hot-plate tests of two compounds isolated from P. pubescens: geranylgeraniol (C1) and 6α,7β-dihydroxyvouacapan-17β-oate methyl ester (C2). This work is a continuation of the previous study investigating the possible mechanisms of action for compounds C1 and C2, and the differences between them. The present study demonstrated that when administered intraperitoneally (i.p.): i), compounds C1 and C2 produced significant anti-allodynic activity during the acute phase of the Complete Freund's Adjuvant (CFA)-induced persistent pain model; ii) compound C1 produced significant anti-hypernociception activity in the carrageenan-induced pain model; iii) compound C2 presented a significant loss of activity after p-chlorophenylalanine methyl ester hydrochloride (PCPA) [5-HT synthesis inhibitor] treatment, suggesting that the mechanisms of action could be related to either the synthesis or release of serotonin; iv) compound C1 presented a significant loss of activity after ondansetron (5-HT(3) receptor antagonist) treatment suggesting activity upon 5-HT(3) serotonin receptors; v) compound C1 presented a significant loss of activity after efaroxan (mixed I(1) imidazoline/α(2)-adrenoceptor antagonist) treatment suggesting the participation of this compound upon imidazoline I(1) receptors; and vi) both compounds C1 and C2 did not appear to exert their activity via 5-HT(1A), 5-HT(2A), imidazoline I(2), α(2)-adrenoceptor, nitric oxide, GABA(A), acetylcholine muscarinic, and nicotinic receptors when evaluated in acetic acid-induced nociception.
AuthorsHumberto M Spindola, Leila Servat, Rodney A F Rodrigues, Ilza M O Sousa, João E Carvalho, Mary A Foglio
JournalEuropean journal of pharmacology (Eur J Pharmacol) Vol. 656 Issue 1-3 Pg. 45-51 (Apr 10 2011) ISSN: 1879-0712 [Electronic] Netherlands
PMID21296068 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCrown Copyright © 2011. Published by Elsevier B.V. All rights reserved.
Chemical References
  • 6alpha,7beta-dihydroxyvouacapan-17beta-oate methyl ester
  • Analgesics
  • Diterpenes
  • Imidazolines
  • Serotonin
  • geranylgeraniol
Topics
  • Analgesics (isolation & purification, pharmacology, therapeutic use)
  • Animals
  • Diterpenes (isolation & purification, pharmacology, therapeutic use)
  • Fabaceae (chemistry)
  • Hyperalgesia (drug therapy, metabolism)
  • Imidazolines (metabolism)
  • Male
  • Mice
  • Serotonin (metabolism)

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