Imidazenil is a highly potentbenzodiazepine receptorpartial agonist[2] with an unusual profile of effects, producing some of the effects associated with normal benzodiazepines such asanticonvulsant andanxiolytic effects, yet without any notablesedative oramnestic[3] effects. In fact, imidazenil blocks the sedative effects ofdiazepam, yet without lowering the convulsion threshold,[4] and so potentially could be a more flexible antidote than the antagonistflumazenil which is commonly used to treatbenzodiazepine overdose at present.
Imidazenil has not yet been developed commercially for use in humans, however it has been suggested as a safe and effective treatment foranxiety,[5] a potent yet non-sedating anticonvulsant which might be particularly useful in the treatment of poisoning with organophosphatenerve agents,[6][7] and as a novel treatment forschizophrenia.[8]
In rats, imidazenil has been demonstrated to have low tolerance or dependence liability, unlike other benzodiazepine receptor agonist ligands, such as diazepam, bretazenil.[9]
Imidazenil is selective over the type ofGABAA receptor it acts on. It acts as a partial agonist on those with a α1β2γ2S composition and as a full agonist on those with a α5β2γ2S composition.[4] Its action can be compared to that ofclobazam, another anxioselective benzodiazepine. Clobazam's active metabliteN-desmethylclobazam has lower affinity on receptors with an α1 subunit compared to those with an α2.[10][11] It is believed that the subjective, ataxic, and sedative properties are mediated via α1-containing receptors, while the anxiolytic effects are mediated via the ones with α2, α3, or α5.[4]
^Thompson DM, Auta J, Guidotti A, Costa E (June 1995). "Imidazenil, a new anxiolytic and anticonvulsant drug, attenuates a benzodiazepine-induced cognition deficit in monkeys".The Journal of Pharmacology and Experimental Therapeutics.273 (3):1307–12.PMID7791102.
^Auta J, Faust WB, Lambert P, Guidotti A, Costa E, Moerschbaecher JM (June 1995). "Comparison of the effects of full and partial allosteric modulators of GABA(A) receptors on complex behavioral processes in monkeys".Behavioural Pharmacology.6 (4):323–332.doi:10.1097/00008877-199506000-00003.PMID11224341.S2CID24584434.
^Atack JR (August 2003). "Anxioselective compounds acting at the GABA(A) receptor benzodiazepine binding site".Current Drug Targets. CNS and Neurological Disorders.2 (4):213–32.doi:10.2174/1568007033482841.PMID12871032.
^Rump S, Gidynska T, Galecka E, Antkowiak O, Nawrocka M, Kowalczyk M (2000). "Effects of imidazenil, a new benzodiazepine receptor partial agonist, in the treatment of convulsions in organophosphate intoxications".Neurotoxicity Research.2 (1):17–22.doi:10.1007/bf03033323.PMID15545002.S2CID2066413.
^Guidotti A, Auta J, Davis JM, Dong E, Grayson DR, Veldic M, et al. (July 2005). "GABAergic dysfunction in schizophrenia: new treatment strategies on the horizon".Psychopharmacology.180 (2):191–205.doi:10.1007/s00213-005-2212-8.PMID15864560.S2CID25147595.
^Auta J, Giusti P, Guidotti A, Costa E (September 1994). "Imidazenil, a partial positive allosteric modulator of GABAA receptors, exhibits low tolerance and dependence liabilities in the rat".J Pharmacol Exp Ther.270 (3):1262–9.PMID7932179.{{cite journal}}: CS1 maint: multiple names: authors list (link)
