Centrally-administered AMPA antagonists increase locomotion in parkinsonian rats.
It was shown in the present study that three antagonists of the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) glutamate receptor, including 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo(f)quinoxaline (NBQX), 1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine (GYKI 52466) and 6-(1H-imidazole-1-yl)-7-nitro-2,3-(1H, 4H)-quinoxalinedione (YM90K), caused marked reversal of akinesia when administered into the entopeduncular nucleus of rats rendered parkinsonian by bilateral substantia nigra pars compacta lesion. These data suggest that centrally active AMPA antagonists may have therapeutic utility in the treatment of idiopathic Parkinson's disease.
Stauch Slusher
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B
Department of Pharmacology, ZENECA Pharmaceuticals, Wilmington, DE, USA.
Rissolo
K C
KC
Anzilotti
K F
KF
Jackson
P F
PF
D000818:Animals; D014151:Anti-Anxiety Agents; D001569:Benzodiazepines / Q000008:administration & dosage / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D008636:Mesencephalon / Q000502:physiology; D008845:Microinjections; D009043:Motor Activity / Q000187:drug effects*; D016627:Oxidopamine; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000523:psychology*; D011810:Quinoxalines / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors*; D013378:Substantia Nigra / Q000502:physiology
D014151:Anti-Anxiety Agents; D018691:Excitatory Amino Acid Antagonists; D011810:Quinoxalines; D018091:Receptors, AMPA; C061950:GYKI 52466; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D001569:Benzodiazepines; C086162:6-(1H-imidazol-1-yl)-7-nitro-2,3(1H,4H)-quinoxalinedione; D016627:Oxidopamine