Modulation of [3H]MK-801 binding to NMDA receptors in vivo and in vitro.

摘要: Abstract [3H]MK-801 binding in vivo was used to determine the occupancy of NMDA receptor ligands shown allosterically modulate vitro. ED50 values (mg/kg) were obtained for channel blockers (+)-5-methyl-10,11-dihydro-5,4-dibenzo[a,d]cyclohepten-5,10-imine maleate ((+)-MK-801, 0.2), 1-(1-phenylcyclohexyl)piperidine (phencyclidine, PCP, 1.7) and ketamine (4.4). Antagonists at glutamate ( dl -(2-carboxypiperazine-4-yl)propyl-1-phosphonate -CPP, 5.7)) glycine site (7-Chloro-4-hydroxy-3-(3-phenoxy)-phenyl-2(H)quinolinone (L-701,324, 14.1), 3R(+)cis-4-methyl-pyrrollid-2-one (L-687,414, 15.1)) inhibited varying maximum levels (69%, 103% 45%, respectively). NR2B subunit-selective compounds acting ifenprodil by a 52–72% gave of: (±)-(1S*,2S*)-1-(4-hydroxyphenyl)-2-(4-hydroxy-4-phenylpiperidino)-1-propanol ((±)CP-101,606), 1.9; (±)-(3R,4S)-3-[4-(4-fluorophenyl)-4-hydroxypiperidin-1-yl]chroman-4,7-diol ((±)CP-283,097), 1.8; (±)-(R*,S*)-α-(4-hydroxyphenyl)-β-methyl-4-(phenylmethyl)-1-piperidine propanol ((±)Ro 25-6981), 1.0; ifenprodil, 6.0. The agonist d -serine stimulated 151% control with an 1.7 mg/kg. Results show that may be measure not only within ion but also modulatory sites on complex.