1371159

Relief of experimental spasticity and anxiolytic/anticonvulsant actions of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate antagonist 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline.

Article date: 1992/2/1

PubMed ID: 1371159

Journal name: The Journal of pharmacology and experimental therapeutics (ISSN: 0022-3565)

ABSTRACT

Spasticity is characterized by pathological overactivity in spinal stretch reflex circuits and may be associated with disturbances in excitatory amino acid-mediated transmission in the cord. A genetically determined syndrome of spasticity in the rat permits the quantitative evaluation of the antispastic effects of drugs by recording activity in the electromyogram (EMG) from a hind limb extensor muscle. In genetically spastic rats, systemic administration of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) antagonist, 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F) quinoxaline (NBQX), normalized pathologically increased EMG activity, whereas the AMPA agonist, alpha-amino-3-hydroxy-5-tertbutyl-4-isoxazolepropionate (ATPA), exacerbated the EMG measures of spasticity. The reflex mechanisms in the spinal cord can be studied in mice using EMG recordings from the tibial muscle (Hoffmann reflex) or from the plantar foot muscle (flexor reflex) after electrical stimulation of the tibial nerve. Systemic and i.t. administration of NBQX blocked Hoffmann reflexes in mice, leaving flexor reflexes unchanged. ATPA enhanced Hoffmann, and had no effect on flexor reflexes. The effects of NBQX on spinal reflexes were seen in doses which do not affect locomotor activity, but show anxiolytic and some antiepileptic activity in rodents. These data suggest that the design of novel muscle relaxant drugs acting at the AMPA subtype of glutamate receptors may be feasible.

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Author List: Turski L, Jacobsen P, Honoré T, Stephens D N

Publication Types: Journal Article

Substances mentioned in the article: Anti-Anxiety Agents; Anticonvulsants; Quinoxalines; 2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; Ibotenic Acid; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid;

Mesh terms: Animals; Anti-Anxiety Agents/pharmacology; Anticonvulsants/pharmacology; Electromyography; Ibotenic Acid/analogs & derivatives; Kindling, Neurologic/drug effects; Locomotion/drug effects; Male; Mice; Muscle Spasticity/drug therapy; Quinoxalines/pharmacology; Rats; Rats, Inbred Strains; Reflex/drug effects; Spinal Cord/drug effects; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid;

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