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

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-HT3 receptor antagonist) treatment suggesting activity upon 5-HT3 serotonin receptors; v) compound C1 presented a significant loss of activity after efaroxan (mixed I1 imidazoline/α2-adrenoceptor antagonist) treatment suggesting the participation of this compound upon imidazoline I1 receptors; and vi) both compounds C1 and C2 did not appear to exert their activity via 5-HT1A, 5-HT2A, imidazoline I2, α2-adrenoceptor, nitric oxide, GABAA, acetylcholine muscarinic, and nicotinic receptors when evaluated in acetic acid-induced nociception.