Prolongation of levodopa responses by glycineB antagonists in parkinsonian primates.
To examine the antiparkinsonian effects of blocking glycineB receptors, we designed a pilot study testing the potent and selective antagonist, PAMQX, in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated primates. PAMQX had no intrinsic effects but markedly potentiated the antiparkinsonian action of levodopa. In a dose-dependent fashion, coadministration of the glycineB antagonist with levodopa extended the response duration by nearly 60%. It is noteworthy that PAMQX, within a considerable dose range, did not cause ataxia or other side effects. These data indicate that blocking N-methyl-D-aspartate receptors selectively to manipulate dopaminergic-mediated motor responses may be produced effectively by glycineB antagonists.
Department of Neurology, Emory University, Atlanta, Georgia 30322, USA. spapa@emory.edu
Stella M
SM
Papa
Yves P
YP
Auberson
J Timothy
JT
Greenamyre
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D000978:Antiparkinson Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001522:Behavior, Animal; D004185:Disability Evaluation; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D018684:Glycine Agents / Q000008:administration & dosage*; D007980:Levodopa / Q000008:administration & dosage / Q000627:therapeutic use*; D008253:Macaca mulatta; D009043:Motor Activity / Q000187:drug effects; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000188:drug therapy*; D010865:Pilot Projects; D011597:Psychomotor Performance / Q000187:drug effects; D018009:Receptors, Glycine / Q000037:antagonists & inhibitors*
D000978:Antiparkinson Agents; D018684:Glycine Agents; D018009:Receptors, Glycine; D007980:Levodopa; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine