Structure and activity of hydrogenated derivatives of (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801).
Several hydrogenated derivatives of the potent NMDA antagonist 1 have been prepared and evaluated as competitive inhibitors of [3H]-1 binding. These compounds were also tested for their ability to act as noncompetitive antagonists of NMDA in vitro. These studies indicate that two aromatic rings are not strictly required for high-affinity binding or NMDA antagonism.
Lyle
T A
TA
Merck Sharp and Dohme Research Laboratories, West Point, Pennsylvania 19486.
Magill
C A
CA
Britcher
S F
SF
Denny
G H
GH
Thompson
W J
WJ
Murphy
J S
JS
Knight
A R
AR
Kemp
J A
JA
Marshall
G R
GR
Middlemiss
D N
DN
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors; D003986:Dibenzocycloheptenes / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D016291:Dizocilpine Maleate; D066298:In Vitro Techniques; D008968:Molecular Conformation; D016202:N-Methylaspartate; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000187:drug effects; D013329:Structure-Activity Relationship
D000927:Anticonvulsants; D003986:Dibenzocycloheptenes; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D001224:Aspartic Acid; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate