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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.