Antinociceptive Profile of (-)-Spectaline: A Piperidine Alkaloid from Cassia leptophylla

Abstract

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 μmol/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 ID₅₀ = 14.68 μmol/kg (4.8 mg/kg), indomethacin ID₅₀ = 0.78 μmol/kg (0.28 mg/kg) and (-)-spectaline ID₅₀ = 48.49 μmol/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 ID₅₀ = 20.81 μg/paw and dipyrone ID₅₀ = 19.89 μg/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.

Key words

Cassia leptophylla Vog. - Leguminosae - (-)-spectaline - antinociceptive

References

• 1 Bolzani V S, Gunatilaka A AL, Kingston D GI. Bioactive and other piperidine alkaloids from Cassia leptophylla .  Tetrahedron. 1995;  51 5929-34
• 2 Banba Y, Abe C, Nemoto H, Kato A, Adachi I, Takahata H. Asymmetric synthesis of fagomine and Its analogues.  Tetrahedron Asymmetry. 2001;  12 817-9
• 3 Zimmerman M. Ethical guidelines for investigation of experimental pain in conscious animals.  Pain. 1983;  16 109-10
• 4 Souza Brito A RM. Manual de ensaios toxicológicos in vivo . Unicamp Campinas, Brasil; 1995
• 5 Litchfield J T, Wilcoxon F A. A simplified method of evaluating dose effect experiments.  J Pharmacol Exp Ther. 1949;  95 99-113
• 6 Koster R, Anderson M, De Beer E J. Acetic acid for analgesic screening.  Fed Proc. 1959;  18 418-20
• 7 Tjolsen A, Berge O G, Hunskaar S, Rosland J N, Hole K. The formalin test: an evaluation of the method.  Pain. 1992;  51 5-17
• 8 Sakurada T, Katsumata K, Tan-No K, Sakurada S, Kisara K. The capsaicin test in mice for evaluating tachykinin antagonists in the spinal cord.  Neurophamacology. 1992;  31 1279-85
• 9 Eddy N B, Leimback D. Synthetic analgesics. II. Dithienylbutenyl and diethylenylbutylamines.  J Pharmacol Exp Ther. 1953;  107 385-93
• 10 D’Amour F E, Smith D L. Method for determining loss of pain sensation.  J Pharmacol Exp Ther. 1941;  72 74-9
• 11 Collier H OJ, Dinneen L C, Johnson C A, Schhneider C. The abdominal constriction response and its supression by analgesic drugs in the mouse.  Br J Pharmacol Chemoth. 1968;  32 295-310
• 12 Hunskaar S, Berger O -G, Hole K. Dissociation between antinociceptive and anti-inflammatory effects of acetylsalicylic acid and indomethacin in the formalin test.  Pain. 1986;  25 125-32
• 13 Hong Y, Abbott F V. Behavioural effects of intra-plantar injection of inflammatory mediators in the rat.  Neuroscience. 1994 ;  63 827-36
• 14 Chapman V, Dickenson A H. The spinal and peripheral roles of bradykinin and prostaglandins in nociceptive processing in the rat.  Eur J Pharmacol. 1992;  219 427-33
• 15 Corrêa C R, Kyle D J, Chakravarty S, Calixto J B. Antinociceptive profile of the pseudopeptide B₂ bradykinin receptor antagonist NPC 18 688 in mice.  Br J Pharmacol. 1996;  117 552-8
• 16 Sugishita E, Amagaya S, Ogihara Y. Anti-inflammatory testing methods: comparative evaluation of mice and rats.  J Pharmacobiod. 1981;  4 565-75
• 17 Santos A RS, Calixto J B. Further evidence for the involvement of tachykinin receptor subtypes in formalin and capsaicin models of pain in mice.  Neuropeptides. 1997;  31 381-9
• 18 Piper A S, Yeats J C, Bevan S, Docherty R J. A study of the voltage dependence of capsaicin-activated membrane currents in rat sensory neurones before and after acute desensitization.  J Physiol. 1999;  518 721-33
• 19 Caterina M j, Schumacher M A, Tominaga M, Rosen T A, Levine J D, Julius D. The capsaicin receptor: a heat-activated ion channel in the pain pathway.  Nature. 2000;  389 816-24
• 20 Davis J B, Gray J, Gunthorpe M J, Hatcher J P, Davey P T, Hughes A S. et al . Vanilloid receptor-1 is essential for inflammatory thermal hyperalgesia.  Nature. 2000;  405 183-7