title: 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.
authors.affiliation: CPQBA, University of Campinas, P.O. Box 6171, 13083-970 Campinas, SP, Brazil. hmspindola@fop.unicamp.br
authors.forename: Humberto M
authors.initials: HM
authors.lastname: Spindola
authors.forename: Leila
authors.initials: L
authors.lastname: Servat
authors.forename: Rodney A F
authors.initials: RA
authors.lastname: Rodrigues
authors.forename: Ilza M O
authors.initials: IM
authors.lastname: Sousa
authors.forename: João E
authors.initials: JE
authors.lastname: Carvalho
authors.forename: Mary A
authors.initials: MA
authors.lastname: Foglio
mesh_terms: D000700:Analgesics / Q000302:isolation & purification* / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D004224:Diterpenes / Q000302:isolation & purification* / Q000494:pharmacology* / Q000627:therapeutic use; D007887:Fabaceae / Q000737:chemistry*; D006930:Hyperalgesia / Q000188:drug therapy / Q000378:metabolism; D048288:Imidazolines / Q000378:metabolism; D008297:Male; D051379:Mice; D012701:Serotonin / Q000378:metabolism
chemical_list: C549020:6alpha,7beta-dihydroxyvouacapan-17beta-oate methyl ester; D000700:Analgesics; D004224:Diterpenes; D048288:Imidazolines; D012701:Serotonin; C017338:geranylgeraniol