Centrally-administered glycine antagonists increase locomotion in monoamine-depleted mice.
It was shown in the present study that several structurally diverse antagonists of the glycine site of the NMDA receptor, including (R)-HA-966, L689,560, 5,7-dichlorokynurenic acid, 7-chlorokynurenic acid, and two of ZENECA's novel pyridazinoindole glycine antagonists, caused marked reversal of akinesia when administered intrastriatally to monoamine depleted mice. Coinjection of the glycine agonist D-serine antagonized this locomotor stimulation. In addition, all glycine antagonists tested did not cause significant locomotor stimulation when intrastriatally administered to normal mice. These data suggest that glycine antagonists may offer therapeutic utility in the treatment of idiopathic Parkinson's disease.
Stauch Slusher
B
B
ZENECA Pharmaceuticals Group, Department of Pharmacology, Wilmington, DE.
Rissolo
K C
KC
Jackson
P F
PF
Pullan
L M
LM
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D015306:Biogenic Monoamines / Q000502:physiology*; D005998:Glycine / Q000037:antagonists & inhibitors*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D011760:Pyrrolidinones / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D012694:Serine / Q000494:pharmacology; D013268:Stimulation, Chemical
D015306:Biogenic Monoamines; D011760:Pyrrolidinones; D016194:Receptors, N-Methyl-D-Aspartate; D012694:Serine; C001369:1-hydroxy-3-amino-2-pyrrolidone; D005998:Glycine