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Nonsteroidal antiinflammatory drug modulation of behavioral responses to intrathecal N-methyl-D-aspartate, but not to substance P and amino-methyl-isoxazole-propionic acid in the rat. 1996

R Björkman, and K M Hallman, and J Hedner, and T Hedner, and M Henning
Division of Clinical Pharmacology, University of Gothenburg, Sweden.

Antinociception by nonsteroidal antiinflammatory drugs, notably diclofenac and S(+)-ibuprofen, has traditionally been attributed to peripheral tissue cyclooxygenase inhibition. This study investigates the potential role of the nitric oxide system for the central antinociceptive effects of diclofenac, S(+)-, and R(-)-ibuprofen. Diclofenac and S(+)- but not R(-)-ibuprofen inhibited the behavioral response dose dependently, "biting, scratching, and licking (BSL)," induced by the spinal application of N-methyl-D-aspartate, but not that of amino-methylisoxazole-propionic acid or substance P. Diclofenac and S(+)-ibuprofen induced a parallel shift in the number of BSL responses and in the duration of the response in the behavioral model at their approximate median effective doses (diclofenac 1 mumol and S(+)-ibuprofen 5 mumol). Pretreatment with L-arginine, the natural substrate for the nitric oxide synthetase, antagonized diclofenac, and S(+)-ibuprofen-induced suppression of the biting, scratching, and licking response evoked by intrathecal N-methyl-D-aspartate. D-arginine did not antagonize the diclofenac- and S(+)-ibuprofen-induced antinociception. The study results indicate that analgesia after diclofenac and S(+)-ibuprofen involves a central mechanism which may add to the peripheral antinociceptive effect of these agents. The central action of diclofenac and S(+)-ibuprofen is partly mediated by an interaction with the N-methyl-D-aspartate receptor and nitric oxide-generating mechanisms.

UI MeSH Term Description Entries
D007052 Ibuprofen A non-steroidal anti-inflammatory agent with analgesic, antipyretic, and anti-inflammatory properties Advil,Benzeneacetic Acid, alpha-methyl-4-(2-methylpropyl)- trimethylsilyl ester,Brufen,Ibumetin,Ibuprofen, (+-)-Isomer,Ibuprofen, (R)-Isomer,Ibuprofen, (S)-Isomer,Ibuprofen, Aluminum Salt,Ibuprofen, Calcium Salt,Ibuprofen, Copper (2+) Salt,Ibuprofen, Magnesium Salt,Ibuprofen, Potassium Salt,Ibuprofen, Sodium Salt,Ibuprofen, Zinc Salt,Ibuprofen-Zinc,Motrin,Nuprin,Rufen,Salprofen,Trauma-Dolgit Gel,alpha-Methyl-4-(2-methylpropyl)benzeneacetic Acid,Ibuprofen Zinc,Trauma Dolgit Gel
D008297 Male Males
D004008 Diclofenac A non-steroidal anti-inflammatory agent (NSAID) with antipyretic and analgesic actions. It is primarily available as the sodium salt. Diclophenac,Dichlofenal,Diclofenac Potassium,Diclofenac Sodium,Diclonate P,Dicrofenac,Feloran,GP-45,840,Novapirina,Orthofen,Orthophen,Ortofen,SR-38,Sodium Diclofenac,Voltaren,Voltarol,Diclofenac, Sodium,GP 45,840,GP45,840,SR 38,SR38
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000894 Anti-Inflammatory Agents, Non-Steroidal Anti-inflammatory agents that are non-steroidal in nature. In addition to anti-inflammatory actions, they have analgesic, antipyretic, and platelet-inhibitory actions. They act by blocking the synthesis of prostaglandins by inhibiting cyclooxygenase, which converts arachidonic acid to cyclic endoperoxides, precursors of prostaglandins. Inhibition of prostaglandin synthesis accounts for their analgesic, antipyretic, and platelet-inhibitory actions; other mechanisms may contribute to their anti-inflammatory effects. Analgesics, Anti-Inflammatory,Aspirin-Like Agent,Aspirin-Like Agents,NSAID,Non-Steroidal Anti-Inflammatory Agent,Non-Steroidal Anti-Inflammatory Agents,Nonsteroidal Anti-Inflammatory Agent,Anti Inflammatory Agents, Nonsteroidal,Antiinflammatory Agents, Non Steroidal,Antiinflammatory Agents, Nonsteroidal,NSAIDs,Nonsteroidal Anti-Inflammatory Agents,Agent, Aspirin-Like,Agent, Non-Steroidal Anti-Inflammatory,Agent, Nonsteroidal Anti-Inflammatory,Anti-Inflammatory Agent, Non-Steroidal,Anti-Inflammatory Agent, Nonsteroidal,Anti-Inflammatory Analgesics,Aspirin Like Agent,Aspirin Like Agents,Non Steroidal Anti Inflammatory Agent,Non Steroidal Anti Inflammatory Agents,Nonsteroidal Anti Inflammatory Agent,Nonsteroidal Anti Inflammatory Agents,Nonsteroidal Antiinflammatory Agents
D001522 Behavior, Animal The observable response an animal makes to any situation. Autotomy Animal,Animal Behavior,Animal Behaviors
D013237 Stereoisomerism The phenomenon whereby compounds whose molecules have the same number and kind of atoms and the same atomic arrangement, but differ in their spatial relationships. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed) Molecular Stereochemistry,Stereoisomers,Stereochemistry, Molecular,Stereoisomer
D013373 Substance P An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of PAIN, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. Euler-Gaddum Substance P,Hypothalamic Substance P,SP(1-11),Euler Gaddum Substance P,Substance P, Euler-Gaddum,Substance P, Hypothalamic
D016202 N-Methylaspartate An amino acid that, as the D-isomer, is the defining agonist for the NMDA receptor subtype of glutamate receptors (RECEPTORS, NMDA). N-Methyl-D-aspartate,NMDA,N-Methyl-D-aspartic Acid,Acid, N-Methyl-D-aspartic,N Methyl D aspartate,N Methyl D aspartic Acid,N Methylaspartate
D017207 Rats, Sprague-Dawley A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company. Holtzman Rat,Rats, Holtzman,Sprague-Dawley Rat,Rats, Sprague Dawley,Holtzman Rats,Rat, Holtzman,Rat, Sprague-Dawley,Sprague Dawley Rat,Sprague Dawley Rats,Sprague-Dawley Rats

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