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 | |
| Publication status | Published - Nov 1990 |
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ASJC Scopus subject areas
- Toxicology
- Pharmacology (medical)
Cite this
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
}
TY - JOUR
T1 - Anti-inflammatory pharmacology and mechanism of the orally active capsaicin analogs, NE-19550 and NE-28345
AU - Brand, L. M.
AU - Skare, K. L.
AU - Loomans, M. E.
AU - Reller, H. H.
AU - Schwen, R. J.
AU - Lade, D. A.
AU - Bohne, R. L.
AU - Maddin, C. S.
AU - Moorehead, D. P.
AU - Fanelli, R.
AU - Chiabrando, C.
AU - Castelli, M. G.
AU - Tai, H. H.
PY - 1990/11
Y1 - 1990/11
N2 - 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.
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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U2 - 10.1007/BF01997628
DO - 10.1007/BF01997628
M3 - Article
VL - 31
SP - 329
EP - 340
JO - Inflammation Research
JF - Inflammation Research
SN - 1023-3830
IS - 3-4
ER -