NE-19550: a novel, orally active anti-inflammatory analgesic.
NE-19550, N-(3-methoxy-4-hydroxybenzyl)oleamide, is a capsaicin analogue that has been shown to possess oral activity in the 55 degrees C rat hot-plate and mouse phenylquinone abdominal constriction analgesia tests. The compound also displayed anti-inflammatory activity orally in the carrageenan-inflamed rat-paw test and topically in the croton oil-inflamed mouse-ear test. NE-19550 activity in the thermal analgesia assay was not blocked by the opioid antagonist naloxone, and no inhibition of prostanoid synthesis in rat platelets or tissues was seen following a high analgesic and anti-inflammatory oral dose (300 mg/kg). A wide variety of known neuronal antagonists (adrenergic, serotonergic, dopaminergic, cholinergic, GABA-ergic, histaminergic) were found not to inhibit NE-19550 analgesia, further indicating a lack of involvement of known drug receptors mediating analgesic responses. Analgesic doses of NE-19550 were also found to lack the acute toxicity and thermoregulatory desensitization characteristics of the parent natural product capsaicin. It appears to represent a new class of potent-acting, non-narcotic, anti-inflammatory analgesic agents.
D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D002211:Capsaicin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000633:toxicity; D003875:Drug Eruptions / Q000188:drug therapy; D005534:Foot Diseases / Q000188:drug therapy; D006358:Hot Temperature / Q000009:adverse effects; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010147:Pain Measurement; D051381:Rats; D011919:Rats, Inbred Strains; D013276:Stomach Ulcer / Q000139:chemically induced
D000894:Anti-Inflammatory Agents, Non-Steroidal; C054256:olvanil; D002211:Capsaicin