Anti-inflammatory pharmacology and mechanism of the orally active capsaicin analogs, NE-19550 and NE-28345

L. M. Brand; K. L. Skare; M. E. Loomans; H. H. Reller; R. J. Schwen; D. A. Lade; R. L. Bohne; C. S. Maddin; D. P. Moorehead; R. Fanelli; C. Chiabrando; M. G. Castelli; H. H. Tai

doi:10.1007/BF01997628

Anti-inflammatory pharmacology and mechanism of the orally active capsaicin analogs, NE-19550 and NE-28345

L. M. Brand, K. L. Skare, M. E. Loomans, H. H. Reller, R. J. Schwen, D. A. Lade, R. L. Bohne, C. S. Maddin, D. P. Moorehead, R. Fanelli, C. Chiabrando, M. G. Castelli, H. H. Tai

Istituto di Ricerche Farmacologiche "Mario Negri"

Research output: Contribution to journal › Article › peer-review

Abstract

We have evaluated the properties of a new class of anti-inflammatory agents derived from capsaicin, using the analogs NE-19550 (N-vanillyloleamide) and NE-28345 (N-oleyl-homovanillamide) as examples. This class displayed an atypical profile in the assays utilized, including 1) anti-edema and antileukocyte migration activity in the rat carrageenan pleurisy assay without suppression of pleural prostanoid synthesis, 2) blockade of human platelet aggregation induced by arachidonate or PAF but not that induced by the PGH₂ analog U-46619, without equivalent inhibition in vitro of mammalian cyclooxygenase or thromboxane synthetase preparations, 3) greater potency and efficacy in the rat implanted sponge assay than in the adjuvant arthritis assay, without inhibition of LTB₄ or 15-HETE synthesis in vitro, 4) stronger topical activity in the mouse croton oil inflamed ear assay than the guinea pig UV erythema assay, and 5) oral activity in the rat carrageenan paw edema assay and mouse phenylquinone abdominal constriction rest combined with failure to induce gastric erosion in rats at therapeutic doses. We conclude that NE-19550 and NE-28345 do not act like conventional NSAIDs via suppression of arachidonic acid metabolism.

Original language	English
Pages (from-to)	329-340
Number of pages	12
Journal	Agents and Actions
Volume	31
Issue number	3-4
DOIs	https://doi.org/10.1007/BF01997628
Publication status	Published - Nov 1990

ASJC Scopus subject areas

Toxicology
Pharmacology (medical)

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Brand, L. M., Skare, K. L., Loomans, M. E., Reller, H. H., Schwen, R. J., Lade, D. A., Bohne, R. L., Maddin, C. S., Moorehead, D. P., Fanelli, R., Chiabrando, C., Castelli, M. G., & Tai, H. H. (1990). Anti-inflammatory pharmacology and mechanism of the orally active capsaicin analogs, NE-19550 and NE-28345. Agents and Actions, 31(3-4), 329-340. https://doi.org/10.1007/BF01997628

Anti-inflammatory pharmacology and mechanism of the orally active capsaicin analogs, NE-19550 and NE-28345. / Brand, L. M.; Skare, K. L.; Loomans, M. E.; Reller, H. H.; Schwen, R. J.; Lade, D. A.; Bohne, R. L.; Maddin, C. S.; Moorehead, D. P.; Fanelli, R.; Chiabrando, C.; Castelli, M. G.; Tai, H. H.

In: Agents and Actions, Vol. 31, No. 3-4, 11.1990, p. 329-340.

Research output: Contribution to journal › Article › peer-review

Brand, L. M. ; Skare, K. L. ; Loomans, M. E. ; Reller, H. H. ; Schwen, R. J. ; Lade, D. A. ; Bohne, R. L. ; Maddin, C. S. ; Moorehead, D. P. ; Fanelli, R. ; Chiabrando, C. ; Castelli, M. G. ; Tai, H. H. / Anti-inflammatory pharmacology and mechanism of the orally active capsaicin analogs, NE-19550 and NE-28345. In: Agents and Actions. 1990 ; Vol. 31, No. 3-4. pp. 329-340.

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abstract = "We have evaluated the properties of a new class of anti-inflammatory agents derived from capsaicin, using the analogs NE-19550 (N-vanillyloleamide) and NE-28345 (N-oleyl-homovanillamide) as examples. This class displayed an atypical profile in the assays utilized, including 1) anti-edema and antileukocyte migration activity in the rat carrageenan pleurisy assay without suppression of pleural prostanoid synthesis, 2) blockade of human platelet aggregation induced by arachidonate or PAF but not that induced by the PGH2 analog U-46619, without equivalent inhibition in vitro of mammalian cyclooxygenase or thromboxane synthetase preparations, 3) greater potency and efficacy in the rat implanted sponge assay than in the adjuvant arthritis assay, without inhibition of LTB4 or 15-HETE synthesis in vitro, 4) stronger topical activity in the mouse croton oil inflamed ear assay than the guinea pig UV erythema assay, and 5) oral activity in the rat carrageenan paw edema assay and mouse phenylquinone abdominal constriction rest combined with failure to induce gastric erosion in rats at therapeutic doses. We conclude that NE-19550 and NE-28345 do not act like conventional NSAIDs via suppression of arachidonic acid metabolism.",

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AU - Schwen, R. J.

AU - Lade, D. A.

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AU - Maddin, C. S.

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AU - Fanelli, R.

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AB - We have evaluated the properties of a new class of anti-inflammatory agents derived from capsaicin, using the analogs NE-19550 (N-vanillyloleamide) and NE-28345 (N-oleyl-homovanillamide) as examples. This class displayed an atypical profile in the assays utilized, including 1) anti-edema and antileukocyte migration activity in the rat carrageenan pleurisy assay without suppression of pleural prostanoid synthesis, 2) blockade of human platelet aggregation induced by arachidonate or PAF but not that induced by the PGH2 analog U-46619, without equivalent inhibition in vitro of mammalian cyclooxygenase or thromboxane synthetase preparations, 3) greater potency and efficacy in the rat implanted sponge assay than in the adjuvant arthritis assay, without inhibition of LTB4 or 15-HETE synthesis in vitro, 4) stronger topical activity in the mouse croton oil inflamed ear assay than the guinea pig UV erythema assay, and 5) oral activity in the rat carrageenan paw edema assay and mouse phenylquinone abdominal constriction rest combined with failure to induce gastric erosion in rats at therapeutic doses. We conclude that NE-19550 and NE-28345 do not act like conventional NSAIDs via suppression of arachidonic acid metabolism.

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Anti-inflammatory pharmacology and mechanism of the orally active capsaicin analogs, NE-19550 and NE-28345

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