A GABAA receptor negative allosteric modulator is a negative allosteric modulator (NAM), or inhibitor, of the GABAA receptor, a ligand-gated ion channel of the major inhibitory neurotransmitter γ-aminobutyric acid (GABA).
[1][2] Non-selective GABAA receptor NAMs can produce a variety of effects including convulsions, neurotoxicity, and anxiety, among others.
[4][5][6] In addition, the selective α5 subunit-containing GABAA receptor NAMs L-655,708 and MRK-016 have been found to produce rapid-acting antidepressant effects in animals similar to those of the NMDA receptor antagonist ketamine, and are of interest for the potential treatment of depression.
[13] Other GABAA NAMs, mostly non-selective, include amentoflavone, bemegride, bilobalide, cicutoxin, dieldrin, FG-7142, fipronil, flurothyl, iomazenil, laudanosine, lindane, oenanthotoxin, pentylenetetrazol, phenylsilatrane, picrotoxin, radequinil, Ro15-4513, sarmazenil, suritozole, terbequinil, tetramethylenedisulfotetramine (TETS), and ZK-93426 as well as the endogenous neurosteroids dehydroepiandrosterone sulfate (DHEA-S), pregnenolone sulfate, epipregnanolone, and isopregnanolone.
Some naturally occurring GABAA receptor NAMs like cicutoxin and picrotoxin are considered to be toxins.