Antinociceptive Profile of Hodgkinsine

Abstract

To further understand the mechanism of analgesic activity and structural requirements of pyrrolidinoindoline alkaloids identified in Psychotria colorata, we here report the analgesic activity of the trimer hodgkinsine on thermal and chemical models of analgesia. Results show that hodgkinsine produces a dose-dependent naloxone reversible analgesic effect in thermal models of nociception, suggesting that activation of opioid receptors participates in hodgkinsine's mode of action. Hodgkinsine shows a potent dose-dependent analgesic activity against capsaicin-induced pain, indicating the participation of NMDA receptors in hodgkinsine-induced analgesia. Such a dual mechanism of action may be of interest for developing innovative analgesics.

References

• 1 Saad H-EA, Saleh EL-S, Shier W T. Biological activities of pyrrolidinoindoline alkaloids from Calycodendron milnei .  Planta Medica. 1995;  61 313-6
• 2 Jannic V, Guéritte F, Laprévote O, Serani L, Martin M T, Sévenet T, Potier P. Pyrrolidinoindoline alkaloids from Psychotria oleoides and Psychotria lyciiflora .  Journal Natural Products. 1999;  62 838-43
• 3 Verotta L, Pilati T, Tatò M, Elisabetsky E, Amador T A, Nunes D S. Pyrrolidinoindoline alkaloids from Psychotria colorata .  Journal Natural Products. 1998;  61 392-6
• 4 Elisabetsky E, Amador T A, Albuquerque R R, Nunes D S, Carvalho A CT. Analgesic activity of Psychotria colorata (Will. Ex R. & S.) Muell. Arg. (Rubiaceae) alkaloids.  Journal of Ethnopharmacology. 1995;  48 77-83
• 5 Amador T A, Elisabetsky E, Souza D O. Effects of Psychotria colorata alkaloids in brain opioid system.  Neurochemical Research. 1996;  21 (1) 97-102
• 6 Elisabetsky E, Amador T A, Leal M B, Nunes D S, Carvalho A CT, Verotta L. Merging ethnopharmacology with chemotaxonomy: an approach to unveil biactive natural products. The case of Psychotria alkaloids as potential analgesics.  Ciência e Cultura. 1997;  49 378-85
• 7 Verotta L, Peterlongo F, Elisabetsky E, Amador T A, Nunes D S. High-performance liquid chromatography-diode array detection-tandem mass spectrometry analyses of the alkaloid extracts of Amazon Psychotria species.  Journal of Chromatography A. 1999;  841 165-76
• 8 Gårdmark M, Urban Höglund A, Hammarlund-Udenaes M. Aspects on tail-flick, hot-plate and electrical stimulation tests for morphine antinociception.  Pharmacology & Toxicology. 1998;  83 252-8
• 9 Sakurada T, Wako K, Sugiyama A, Sakurada C, Tan-No K, Kisara K. Involvement of spinal NMDA receptors in capsaicin-induced nociception.  Pharmacology Biochemical and Behavior. 1998;  59 (2) 339-45
• 10 Galli A, Renzi G, Bartolini R, Aiello-Malmerg P, Bartolini A. Reversible inhibition of acetylcholinesterase by eseroline, an agonist structurally related to physostigmine (eserine) and morphine.  Biochemical Pharmacology. 1982;  31 (7) 1233-8
• 11 Schonenberger B, Jacobson A E, Brossi A, Streaty R, Klee W A, Flippen-Anderson J L, Gilardi R. Comparation of (-)-eseroline with (+)-eseroline and dihidroseco analogs in antinociceptive assays: confirmation of rubeserine structure by X-ray analysis.  Journal of Medicinal Chemistry. 1986;  29 (11) 2268-73
• 12 Dickenson A H, Chapman V, Green G M. The pharmacology of excitatory and inhibitory amino acid-mediated events int he transmission and modulation of pain in the spinal cord.  General Pharmacology. 1997;  28 (5) 633-8
• 13 Dickenson A H. NMDA receptor antagonists: interactions with opioids.  Acta Anaesthesiology Scandinava. 1997;  41 112-5
• 14 Woolfe G, Mac Donald A D. The evaluation of analgesic action of petidine hydrochloride (Bemerol).  Journal Pharmacology and Experimental Therapeutics. 1944;  80 300
• 15 Corrêa C R, Kyle D J, Chakravarty S, Calixto J B. Antinociceptive profile of the pseudopeptide B2 bradykinin receptor antagonist NPC 18688 in mice.  British Journal of Pharmacology. 1996;  110 552-8