D-cycloserine: a ligand for the N-methyl-D-aspartate coupled glycine receptor has partial agonist characteristics.
We have previously shown that D-cycloserine displaces [3H]glycine binding to a recognition site with properties consistent with an N-methyl-D-aspartate (NMDA) receptor modulatory site. Additionally, D-cycloserine positively modulates the NMDA receptor as evidenced by its dose-dependent enhancement of [3H]1-[1-(2-thienyl)cyclohexyl]piperidine ([3H]TCP) binding to the NMDA receptor-coupled ionophore. Further evaluation of this compound indicates that the maximal stimulation of [3H]TCP binding induced by D-cycloserine is lower than that produced by other compounds acting at the NMDA receptor associated glycine modulatory site (glycine and D-serine). Moreover, the stimulation of [3H]TCP binding induced by D-cycloserine in the presence of various fixed concentrations of glycine results in a family of dose-response curves which asymptotically converge to 40-50% of the maximal stimulation induced by glycine alone. These results are consistent with D-cycloserine acting as a partial agonist of the NMDA receptor via its interaction with the coupled glycine modulatory site.
Hood
W F
WF
Central Nervous System Diseases Research, G.D. Searle & Co., St. Louis, MO 63198.
Compton
R P
RP
Monahan
J B
JB
D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003523:Cycloserine / Q000494:pharmacology*; D008297:Male; D010622:Phencyclidine / Q000031:analogs & derivatives / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D018009:Receptors, Glycine; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000378:metabolism*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
D018009:Receptors, Glycine; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; C012058:tenocyclidine; D003523:Cycloserine; D010622:Phencyclidine