Glycinergic interventions potentiate the ability of MK 801 to raise the threshold voltage for tonic hindlimb extension in mice.
Milacemide, an acylated prodrug of glycine, was able to increase the efficacy with which [+]-5-methyl-10,11-dihydro-5h-dibenzo[a,d]cyclohepten-5,10-imine meleate (MK 801) antagonized the electrical precipitation of seizures in mice. The mechanism of milacemide's potentiation of MK 801's antiseizure efficacy in intact mice is unclear; however, a glycine agonist selective for the strychnine-insensitive site on the NMDA receptor complex was also able to potentiate MK 801. The exciting possibility exists that an exogenous glycinergic intervention can potentiate NMDA-mediated neural transmission in intact animals.
Norris
D O
DO
Psychiatry Service, Department of Veterans Affairs Medical Center, Washington, DC 20422.
Mastropaolo
J
J
O'Connor
D A
DA
Novitzki
M R
MR
Deutsch
S I
SI
D000081:Acetamides / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003523:Cycloserine / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004558:Electric Stimulation; D004597:Electroshock; D005998:Glycine / Q000502:physiology*; D006614:Hindlimb / Q000502:physiology; D008297:Male; D051379:Mice; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D012018:Reflex / Q000187:drug effects*
D000081:Acetamides; D008996:Monoamine Oxidase Inhibitors; C039332:milacemide; D016291:Dizocilpine Maleate; D003523:Cycloserine; D005998:Glycine