Abstract
Antinociceptive activity of intracerebroventricularly administered ketorolac tromethamine was evaluated in mice by measuring inhibition of abdominal stretching induced by p-phenylquinone. Ketorolac tromethamine produced dose-dependent antinociception with an ED50 of 7.34 micrograms/mouse (4.97-10.82) and a maximal effect at 30 micrograms. Selective antagonists of opioid receptors were used to determine ketorolac's mechanism of action. The ketorolac tromethamine-induced antinociception was not blocked by the mu- and delta-opioid receptor antagonists, naloxone and ICI-174,864 (N,N-diallyl-Tyr-Aib-Aib-Phe-Leu), respectively; however, the kappa-opioid receptor antagonist nor-binaltorphimine dihydrochloride significantly blocked this effect. These findings suggest that activation of kappa-opioid receptors appears to play a role in the mechanism of the antinociceptive effect of ketorolac tromethamine. Ketorolac tromethamine may induce the release of endogenous kappa-opioids to produce central nervous system antinociception.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Analgesia
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Analgesics, Non-Narcotic / administration & dosage
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Analgesics, Non-Narcotic / antagonists & inhibitors*
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Analgesics, Non-Narcotic / toxicity
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Analysis of Variance
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Animals
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Benzoquinones / pharmacology
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Dose-Response Relationship, Drug
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Drug Interactions
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Enkephalin, Leucine / administration & dosage
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Enkephalin, Leucine / analogs & derivatives
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Enkephalin, Leucine / pharmacology
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Injections, Intraventricular
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Ketorolac Tromethamine
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Male
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Mice
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Mice, Inbred ICR
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Naloxone / administration & dosage
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Naloxone / pharmacology
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Naltrexone / administration & dosage
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Naltrexone / analogs & derivatives*
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Naltrexone / pharmacology
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Narcotic Antagonists / administration & dosage
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Narcotic Antagonists / pharmacology
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Receptors, Opioid, delta / drug effects
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Receptors, Opioid, delta / metabolism
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Receptors, Opioid, kappa / drug effects
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Receptors, Opioid, kappa / metabolism
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Receptors, Opioid, mu / drug effects
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Receptors, Opioid, mu / metabolism
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Tolmetin / administration & dosage
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Tolmetin / analogs & derivatives*
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Tolmetin / antagonists & inhibitors
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Tolmetin / toxicity
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Tromethamine / administration & dosage
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Tromethamine / analogs & derivatives*
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Tromethamine / toxicity
Substances
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Analgesics, Non-Narcotic
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Benzoquinones
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Narcotic Antagonists
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Receptors, Opioid, delta
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Receptors, Opioid, kappa
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Receptors, Opioid, mu
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Tromethamine
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phenylbenzoquinone
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Naloxone
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norbinaltorphimine
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Ketorolac Tromethamine
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Enkephalin, Leucine
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Naltrexone
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N,N-diallyl-tyrosyl-alpha-aminoisobutyric acid-phenylalanyl-leucine
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Tolmetin