Injection of excitatory amino acid antagonists into the medial pallidal segment of a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treated primate reverses motor symptoms of parkinsonism.
Intracerebral injections of the broad spectrum excitatory amino acid antagonist kynurenic acid (50 ug) alleviated the symptoms of akinesia, tremor and rigidity in a severely parkinsonian monkey. Unilateral injection of kynurenic acid within the medial pallidal segment produced rotational behaviour away from the side of the injection, and the limbs on the contralateral side showed relief of the MPTP-induced parkinsonian symptoms. The subsequent bilateral injection of the excitatory amino acid antagonist allowed the monkey to move freely, unhindered by tremor or rigidity. In addition unilateral injections of the NMDA antagonist MK-801 (5, 25 and 50 ug) within the medial pallidum also produced dose-related rotational behaviour, with alleviation of parkinsonian symptoms in the contralateral limbs. Systemic administration of MK-801 (1 ng/kg - 1 ug/kg i.m.) was without effect.
Graham
W C
WC
Department of Cell and Structural Biology, University of Manchester Medical School, U.K.
Robertson
R G
RG
Sambrook
M A
MA
Crossman
A R
AR
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000596:Amino Acids / Q000037:antagonists & inhibitors*; D000818:Animals; D016291:Dizocilpine Maleate / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D005917:Globus Pallidus / Q000187:drug effects; D007260:Infusion Pumps; D007736:Kynurenic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D008252:Macaca fascicularis; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000188:drug therapy*
D000596:Amino Acids; D016291:Dizocilpine Maleate; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D007736:Kynurenic Acid