Anti-inflammatory pharmacology and mechanism of the orally active capsaicin analogs, NE-19550 and NE-28345.
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.
Brand
L M
LM
Procter & Gamble Company, Cincinnati, OH 45239.
Skare
K L
KL
Loomans
M E
ME
Reller
H H
HH
Schwen
R J
RJ
Lade
D A
DA
Bohne
R L
RL
Maddin
C S
CS
Moorehead
D P
DP
Fanelli
R
R
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use*; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D001169:Arthritis, Experimental / Q000188:drug therapy; D002211:Capsaicin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D002351:Carrageenan; D002465:Cell Movement / Q000187:drug effects; D004487:Edema / Q000188:drug therapy / Q000473:pathology; D006168:Guinea Pigs; D007249:Inflammation / Q000188:drug therapy*; D007962:Leukocytes / Q000473:pathology; D008297:Male; D051379:Mice; D010031:Otitis / Q000188:drug therapy; D010975:Platelet Aggregation Inhibitors; D010998:Pleurisy / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D051381:Rats; D011919:Rats, Inbred Strains; D014641:Vanillic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001095:Arachidonic Acids; D010975:Platelet Aggregation Inhibitors; C068206:N-oleylhomovanillamide; D016718:Arachidonic Acid; C054256:olvanil; D002351:Carrageenan; D014641:Vanillic Acid; D002211:Capsaicin