Evidence for a role of 5-HT(1A) receptor on antinociceptive action from Geissospermum vellosii.

ETHNOPHARMACOLOGICAL RELEVANCE: Geissospermum vellosii is a tree widely found throughout the Amazonic forest and frequently used by the native population for painful disorders. AIM OF THE STUDY: The present study examined the antinociceptive effects of Geissospermum vellosii in behavioral models of nociception. MATERIALS, METHODS AND RESULTS: Oral administration of crude extract of Geissospermum vellosii or its dichloromethane fraction (1-100 mg/kg) inhibited formalin-induced inflammatory nociception and acetic acid-induced visceral nociception. The antinociceptive effect of Geissospermum vellosii was unrelated with motor dysfunctions. Furthermore, the alkaloid 12-metoxy-1-methyl-aspidospermidine (0.001-1 mg/kg), isolated from the dichloromethane fraction, also produced antinociception. The antinociception caused by the dichloromethane fraction was significantly attenuated by pre-treatment of mice with p-chlorophenylalanine methyl ester (PCPA, an inhibitor of serotonin synthesis, 100 mg/kg once a day for 4 consecutive days) and WAY-100635 (a 5-HT(1A) receptor antagonist, 0.3 mg/kg). In contrast, dichloromethane fraction antinociception was not affected by pre-treatment of animals with ketanserin (a 5-HT(2) receptor antagonist, 0.3 mg/kg) or ondansetron (a 5-HT(3) receptor antagonist, 0.5 mg/kg). CONCLUSIONS: Together, these results indicate that Geissospermum vellosii produces antinociception through an interaction with 5-HT(1A) receptors. Furthermore, the alkaloid 12-metoxy-1-methyl-aspidospermidine contributes to the antinociceptive properties reported for Geissospermum vellosii.