THE AMPA RECEPTOR ANTAGONIST NBQX EXERTS ANTIDYSTONIC EFFECTS IN AN ANIMAL-MODEL OF IDIOPATHIC DYSTONIA

The effects of the AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate) antagonist NBQX (2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline) were studied in an inbred line of Syrian golden hamsters with paroxysmal dystonia. The severity of dystonia in these mutant hamsters was significantly reduced by NBQX at doses of 10-20 mg/kg i.p. Coadministration of the transport inhibitor probenecid prolonged the antidystonic action of NBQX, indicating that NBQX may be rapidly eliminated by a process sensitive to probenecid. A similar potent and long-lasting antidystonic effect was obtained when NBQX was administered as an aqueous suspension rather than an aqueous solution, which may be explained by retarded absorption of NBQX after its injection as a suspension. The antidystonic activity of the AMPA antagonist NBQX may indicate that an overactivity of excitatory acidergic neurotransmission is involved in the pathophysiology of dystonia in genetically dystonic hamsters.