Inhibition of [3H]-MK801 binding and protection against NMDA-induced lethality in mice by a series of imipramine analogs.
A series of imipramine analogs were tested for inhibition of [3H]-MK801 binding and for their ability to protect against NMDA-induced lethality in mice. The structure-activity relationship (SAR) for the inhibition of [3H]-MK801 binding found primary amines on short linkers to be optimum. For protection against NMDA lethality, compounds containing an unsaturated link to a cyclic amine were the most potent analogs tested. Possible explanations for the lack of correlation observed are briefly discussed.
McQuaid
L A
LA
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285.
Leander
J D
JD
Mendelsohn
L G
LG
Smith
E C
EC
Lawson
R R
RR
Mason
N R
NR
D000818:Animals; D001667:Binding, Competitive; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007099:Imipramine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D008297:Male; D051379:Mice; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D016548:Prosencephalon / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship
D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D007099:Imipramine