PMID: 9549656Apr 29, 1998Paper

Preclinical enantioselective pharmacology of (R)- and (S)- ketorolac

Journal of Clinical Pharmacology
D A HandleyJ R McCullough

Abstract

Many of the nonsteroidal anti-inflammatory drugs (NSAIDs) are marketed as racemic mixtures, composed of (R)- and (S)- enantiomers. Racemic NSAIDs are potent cyclooxygenase (COX) inhibitors only through the action of the (S)- enantiomers, as the (R)- enantiomers do not exhibit COX inhibition. However, the (R)- enantiomer of ketoprofen exhibits potent analgesic activity and minimal ulcerogenic potential. To extend these observations, we examined the (R)- and (S)- enantiomers of RS- ketorolac, (S)- ketorolac exhibited potent COX1 and COX2 enzyme inhibition, whereas (R)- ketorolac was > 100-fold less active on both COX subtypes. Both enantiomers did not affect norepinephrine or serotonin uptake sites, and nitric oxidase or lipoxygenase activities, nor did they demonstrate any affinity for opioid receptors (mu, delta, or kappa). In experimental models, (S)- ketorolac exhibited about 10-fold greater activity than (R)- ketorolac in the murine phenylquinone writhing model. In this model, morphine sulfate was effective at much lower doses, however, and neither (R)- nor (S)- ketorolac showed any morphine-sparing effect. In the rat gait test for analgesia in the foot paw after injection of brewers yeast suspension, neither (R)- nor (S)- k...Continue Reading

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Citations

Feb 8, 2008·Annals of Allergy, Asthma & Immunology : Official Publication of the American College of Allergy, Asthma, & Immunology·Leonard Bielory, Andrey Leonov
May 25, 2010·Journal of Neurochemistry·Matthew W BuczynskiEdward A Dennis
Aug 5, 2015·Assay and Drug Development Technologies·Tudor I Oprea, John P Overington
Mar 23, 2011·Journal of Endodontics·Casey L TurnerWalter R Bowles
Nov 13, 2015·PloS One·Tudor I OpreaAngela Wandinger-Ness
Jul 28, 2019·Cancers·Laurie G HudsonAngela Wandinger-Ness
Sep 6, 2005·Journal of the American Animal Hospital Association·Stephen L CurryJames L Cook
Sep 18, 2007·Current Opinion in Allergy and Clinical Immunology·Andrey Leonov, Leonard Bielory
Jun 14, 2015·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Yuna GuoLaurie G Hudson
Jan 9, 2021·BMC Cancer·Martha M GrimesLaurie G Hudson

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