A novel treatment of global cerebral ischaemia with a glycine partial agonist.
Chronic treatment of gerbils with 1-aminocyclopropanecarboxylic acid (a high affinity, partial agonist at strychnine-insensitive glycine receptors) resulted in a 3-fold increase in survival, a significant improvement in neurological status, and an extensive protection of vulnerable brain regions following severe forebrain ischaemia. A bolus of 1-aminocyclopropanecarboxylic acid 30 min prior to ischaemia did not further improve outcome compared to gerbils receiving their last injection 24 h prior to ischaemia. These findings are consistent with the hypothesis that chronic treatment with a glycine partial agonist desensitizes the N-methyl-D-aspartate receptor complex. Pharmacological intervention at the strychnine-insensitive glycine receptor may be an effective means of ameliorating the consequences of neuronal degeneration caused by excitotoxic phenomena.
Von Lubitz
D K
DK
Department of Biochemistry, Hahnemann University, Philadelphia, PA 19102.
Lin
R C
RC
McKenzie
R J
RJ
Devlin
T M
TM
McCabe
R T
RT
Skolnick
P
P
D000596:Amino Acids / Q000627:therapeutic use*; D000598:Amino Acids, Cyclic; D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy*; D005260:Female; D005849:Gerbillinae; D018009:Receptors, Glycine; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects; D017981:Receptors, Neurotransmitter / Q000187:drug effects*
D000596:Amino Acids; D000598:Amino Acids, Cyclic; D018009:Receptors, Glycine; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; C023863:1-aminocyclopropane-1-carboxylic acid