Antinociceptive profile of (-)-spectaline: a piperidine alkaloid from Cassia leptophylla.
The antinociceptive activity of (-)-spectaline (1), a piperidine alkaloid isolated from Cassia leptophylla Vog. (Leguminosae), was investigated. We have also studied the acute oral toxicity of 1 in mice and it did not show any signals of toxicity in doses lower than 400 micromol/kg. The antinociceptive effect of 1 was evaluated on chemical (acetic acid, formalin and capsaicin) and thermal (hot plate and tail flick) pain models in mice, using classical standard drugs. Dipyrone ID (50) = 14.68 micromol/kg (4.8 mg/kg), indomethacin ID (50) = 0.78 micromol/kg (0.28 mg/kg) and (-)-spectaline ID (50) = 48.49 micromol/kg (15.75 mg/kg), all produced a significant inhibition of acetic acid-induced abdominal writhing in mice. (-)-Spectaline was inactive in the hyperalgesic model of formalin and did not show any central analgesic activity (hot plate and tail flick models). In the capsaicin-induced neurogenic pain model, (-)-spectaline presented an important inhibitory effect with an ID (50) = 20.81 microg/paw and dipyrone ID (50) = 19.89 microg/paw. The ensemble of results permitted us to identify 1 as an antinociceptive compound. The mechanism underlying this antinociceptive effect of 1 remains unknown, but the results suggest that such an effect could be related to pathways associated to vanilloid receptor systems.
NuBBE-Núcleo de Bioensaios, Biossíntese e Ecofisiologia de Produtos Naturais, Universidade Estadual Paulista, Instituto de Química, São Paulo, Brazil.
Magna Suzana
MS
Alexandre-Moreira
Claudio
C
Viegas
Ana Luisa
AL
Palhares de Miranda
Vanderlan da Silva
Vda S
Bolzani
Eliezer J
EJ
Barreiro
D019342:Acetic Acid; D000470:Alkaloids / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use / Q000633:toxicity; D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D000818:Animals; D002211:Capsaicin; D002366:Cassia; D004177:Dipyrone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D035264:Flowers; D005557:Formaldehyde; D005638:Fruit; D006358:Hot Temperature; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D051379:Mice; D010146:Pain / Q000517:prevention & control*; D008517:Phytotherapy; D010880:Piperidines / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use* / Q000633:toxicity*; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use
D000470:Alkaloids; D000700:Analgesics; D010880:Piperidines; D010936:Plant Extracts; C480880:spectaline; D005557:Formaldehyde; D004177:Dipyrone; D019342:Acetic Acid; D002211:Capsaicin; D007213:Indomethacin