Muscle relaxant action of excitatory amino acid antagonists.
Antagonists of neuronal excitation induced by dicarboxylic amino acids were tested in genetically spastic rats of the Han-Wistar strain. These animals exhibit an increased muscle tone which can be measured as a spontaneous tonic activity in the electromyogram of the gastrocnemius-soleus muscle. Compounds that block excitation due to N-methyl-D-aspartic acid reduced the spontaneous activity measured in the electromyogram in a dose-related manner. The most potent compounds, 2-amino-7-phosphonoheptanoic and kynurenic acids were effective muscle relaxants when given either intraperitoneally or intracerebroventricularly. 2-Amino-5-phosphonopentanoic acid possessed much weaker muscle relaxant activity, while L-glutamic acid diethylester was inactive by either route. The results suggest that blockade of N-methyl-D-aspartic acid receptors results in a myorelaxant effect. Specific antagonists of excitation at N-methyl-D-aspartic acid receptors may provide a new class of muscle relaxants.
Turski
L
L
Schwarz
M
M
Turski
W A
WA
Klockgether
T
T
Sontag
K H
KH
Collins
J F
JF
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives; D000596:Amino Acids / Q000037:antagonists & inhibitors* / Q000627:therapeutic use; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D005260:Female; D005971:Glutamates / Q000627:therapeutic use; D007736:Kynurenic Acid / Q000627:therapeutic use; D008297:Male; D009125:Muscle Relaxants, Central; D009128:Muscle Spasticity / Q000188:drug therapy*; D016202:N-Methylaspartate; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000187:drug effects; D014633:Valine / Q000031:analogs & derivatives / Q000627:therapeutic use
D000596:Amino Acids; D005971:Glutamates; D009125:Muscle Relaxants, Central; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; C011829:glutamic acid diethyl ester; D001224:Aspartic Acid; D016202:N-Methylaspartate; D015763:2-Amino-5-phosphonovalerate; D007736:Kynurenic Acid; D014633:Valine; C031231:2-amino-7-phosphonoheptanoic acid