The analgesic and anti-inflammatory profile of (±)-5-benzoyl-1,2-dihydro-3H-pyrrolo[1,2a]pyrrole-1-carboxylic acid (RS-37619)

Abstract

RS-37619 showed highly potent analgesic activity when given p.o. in tests utilizing underlying inflammation. It inhibited phenylquinone-induced writhing in the mouse and rat (350 and 180 x aspirin respectively) and the pain induced by flexing the adjuvant-inflamed rat paw (approximately 800 x aspirin). The agent increased the pain threshold of compressed yeast-inflamed rat paws (3-10 x naproxen). RS-37619 did not increase the pain threshold of the non-inflamed paw and was inactive in the mouse hot plate test; therefore it is probably not a centrally acting or morphine-like agent. RS-37619 was also highly active p.o. in rat models of acute and chronic inflammation. It inhibited carrageenan-induced paw edema (36 x phenylbutazone), cotton pellet-induced granuloma (less than or equal to 1 x indomethacin) and in an 18-day test, prevented the development of adjuvant-induced arthritis (approximately 2 x naproxen). RS-37619 exhibited antiphlogistic activity in adrenalectomized rats. It did not have corticosteroid activity. When given p.o., RS-37619 lowered yeast-induced pyrexia (20 x aspirin). Gastrointestinal irritation was seen in the rat with doses greater than or equal to 6.4 mg/kg/day p.o. The agent elicited mild CNS and cardiovascular activity only at doses far in excess of those required for analgesic and anti-inflammatory activity.

Stereoselective pharmacokinetics of ketorolac in calves after a single intravenous and oral dose

“…The S:R activity ratios of the enantiomers for the anti‐inflammatory and analgesic effect are 57 and 230 in the rat carregenan and mouse writhing assay, respectively, suggesting that the S‐isomer is biologically more active than the R‐isomer (Brocks & Jamali, 1992). KT is a potent inhibitor of the cyclooxygenase pathway of arachidonic acid metabolism, resulting in a decrease in prostaglandin and thromboxane production (Rooks et al. , 1982).…”

Pharmacologic Properties of Ketorolac Tromethamine: A Potent Analgesic Drug

“…Ketorolac, like other NSAIDs, is able to inhibit prostaglandin synthesis (88), both peripherally (85) and spinally (55). Because ketorolac exhibits greater efficacy than other NSAIDs, it has been proposed that its efficacy may involve other mechanisms of action.…”

“…Tests in rats have shown a low incidence of gastrointestinal damage induced by ketorolac administration (88). Certain patients developed, however, gastric antral ulceration after receiving 90 mg of intramuscular ketorolac four times daily (48).…”

The efficacy of intravenous ketorolac for pain relief in single-stage adjustable strabismus surgery: a prospective, randomized, placebo-controlled trial

“…Ketorolac is a non-steroidal anti-inflammatory drug (NSAID) with a 6 h half-life. 7 It has been reported to have fewer side effects than narcotic analgesics, resulting in notably less sedation, nausea, and respiratory depression. [8][9][10] These properties make ketorolac a potential solution for pain control in patients undergoing strabismus surgery.…”