Neuropharmacological characterization of 1-aminocyclopropane-1-carboxylate and 1-aminocyclobutane-1-carboxylate, ligands of the N-methyl-D-aspartate-associated glycine receptor.
Following intravenous administration, 1-aminocyclobutane-1-carboxylate (ACBC, 100 mg/kg), a N-methyl-D-aspartate (NMDA)-associated glycine receptor antagonist, was eliminated with a T1/2 of 5 min in mouse brain and 4 min in rat cerebrospinal fluid (CSF). 1-Aminocyclopropane-1-carboxylate (ACC), a NMDA-associated glycine receptor agonist, was found to have a T1/2 of less than 5 min in mouse brain. ACC and ACBC did not alter basal cerebellar cGMP. Glycine and D-serine increased cGMP, and 1-hydroxy-3-aminopyrrolidone-2 (HA-966), a glycine antagonist, reversed the D-serine-induced increases in cGMP. In contrast, ACBC did not reverse the D-serine-induced increases in cGMP. These data suggest that despite their brain bioavailability and marked potency at the glycine receptor in vitro, ACC and ACBC are rapidly inactivated and thus have limited in vivo utility.
Rao
T S
TS
CNS Diseases Research, G. D. Searle & Company, St. Louis, MO 63198.
Cler
J A
JA
Compton
R P
RP
Emmett
M R
MR
Mick
S
S
Sun
E T
ET
Iyengar
S
S
Wood
P L
PL
D000596:Amino Acids / Q000134:cerebrospinal fluid / Q000494:pharmacology*; D000598:Amino Acids, Cyclic; D000818:Animals; D001682:Biological Availability; D001923:Brain Chemistry / Q000187:drug effects*; D008401:Gas Chromatography-Mass Spectrometry; D005998:Glycine / Q000494:pharmacology; D006207:Half-Life; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D051379:Mice; D011760:Pyrrolidinones / Q000494:pharmacology; D051381:Rats; D018009:Receptors, Glycine; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D012694:Serine / Q000494:pharmacology
D000596:Amino Acids; D000598:Amino Acids, Cyclic; D011760:Pyrrolidinones; D018009:Receptors, Glycine; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; C016987:1-aminocyclobutanecarboxylic acid; C023863:1-aminocyclopropane-1-carboxylic acid; D012694:Serine; C001369:1-hydroxy-3-amino-2-pyrrolidone; D005998:Glycine