Imidazenil

{{Short description|Benzodiazepine drug}}

{{Drugbox

| verifiedrevid = 447928757

| IUPAC_name = 6-(2-Bromophenyl)-8-fluoro-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carboxamide

| image = Imidazenil structure.svg

| image_class = skin-invert-image

| width = 200

| image2 = Imidazenil ball-and-stick model.png

| tradename =

| pregnancy_AU =

| pregnancy_US =

| pregnancy_category =

| legal_AU =

| legal_CA =

| legal_UK =

| legal_US =

| legal_status =

| routes_of_administration =

| bioavailability =

| protein_bound =

| metabolism =

| elimination_half-life =

| excretion =

| CAS_number_Ref = {{cascite|correct|??}}

| CAS_number = 151271-08-8

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = 7N95V6864R

| ATC_prefix = none

| ATC_suffix =

| PubChem = 119194

| DrugBank_Ref = {{drugbankcite|correct|drugbank}}

| DrugBank =

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| ChemSpiderID = 106482

| C=18 | H=12 | Br=1 | F=1 | N=4 | O=1

| smiles = Brc4ccccc4C/2=N/Cc1c(ncn1c3c\2cc(F)cc3)C(=O)N

| StdInChI_Ref = {{stdinchicite|correct|chemspider}}

| StdInChI = 1S/C18H12BrFN4O/c19-13-4-2-1-3-11(13)16-12-7-10(20)5-6-14(12)24-9-23-17(18(21)25)15(24)8-22-16/h1-7,9H,8H2,(H2,21,25)

| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

| StdInChIKey = OCJHYHKWUWSHEN-UHFFFAOYSA-N

}}

Imidazenil{{cite patent | country = US | number = 5317018 }} is an experimental anxiolytic drug which is derived from the benzodiazepine family, and is most closely related to other imidazobenzodiazepines such as midazolam, flumazenil, and bretazenil.

Imidazenil is a highly potent benzodiazepine receptor partial agonist{{cite journal | vauthors = Thompson DM, Auta J, Guidotti A, Costa E | title = Imidazenil, a new anxiolytic and anticonvulsant drug, attenuates a benzodiazepine-induced cognition deficit in monkeys | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 273 | issue = 3 | pages = 1307–12 | date = June 1995 | pmid = 7791102 }} with an unusual profile of effects, producing some of the effects associated with normal benzodiazepines such as anticonvulsant and anxiolytic effects, yet without any notable sedative or amnestic{{cite journal | vauthors = Auta J, Faust WB, Lambert P, Guidotti A, Costa E, Moerschbaecher JM | title = Comparison of the effects of full and partial allosteric modulators of GABA(A) receptors on complex behavioral processes in monkeys | journal = Behavioural Pharmacology | volume = 6 | issue = 4 | pages = 323–332 | date = June 1995 | pmid = 11224341 | doi = 10.1097/00008877-199506000-00003 | s2cid = 24584434 }} effects. In fact, imidazenil blocks the sedative effects of diazepam, yet without lowering the convulsion threshold,{{cite journal | vauthors = Auta J, Costa E, Davis JM, Guidotti A | title = Imidazenil: an antagonist of the sedative but not the anticonvulsant action of diazepam | journal = Neuropharmacology | volume = 49 | issue = 3 | pages = 425–9 | date = September 2005 | pmid = 15964602 | doi = 10.1016/j.neuropharm.2005.04.005 | s2cid = 44619421 }} and so potentially could be a more flexible antidote than the antagonist flumazenil which is commonly used to treat benzodiazepine 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 for anxiety,{{cite journal | vauthors = Atack JR | title = Anxioselective compounds acting at the GABA(A) receptor benzodiazepine binding site | journal = Current Drug Targets. CNS and Neurological Disorders | volume = 2 | issue = 4 | pages = 213–32 | date = August 2003 | pmid = 12871032 | doi = 10.2174/1568007033482841 }} a potent yet non-sedating anticonvulsant which might be particularly useful in the treatment of poisoning with organophosphate nerve agents,{{cite journal | vauthors = Rump S, Gidynska T, Galecka E, Antkowiak O, Nawrocka M, Kowalczyk M | title = Effects of imidazenil, a new benzodiazepine receptor partial agonist, in the treatment of convulsions in organophosphate intoxications | journal = Neurotoxicity Research | volume = 2 | issue = 1 | pages = 17–22 | date = 2000 | pmid = 15545002 | doi = 10.1007/bf03033323 | s2cid = 2066413 }}{{cite journal | vauthors = Auta J, Costa E, Davis J, Guidotti A | title = Imidazenil: a potent and safe protective agent against diisopropyl fluorophosphate toxicity | journal = Neuropharmacology | volume = 46 | issue = 3 | pages = 397–403 | date = March 2004 | pmid = 14975695 | doi = 10.1016/j.neuropharm.2003.09.010 | s2cid = 41221807 }} and as a novel treatment for schizophrenia.{{cite journal | vauthors = Guidotti A, Auta J, Davis JM, Dong E, Grayson DR, Veldic M, Zhang X, Costa E | display-authors = 6 | title = GABAergic dysfunction in schizophrenia: new treatment strategies on the horizon | journal = Psychopharmacology | volume = 180 | issue = 2 | pages = 191–205 | date = July 2005 | pmid = 15864560 | doi = 10.1007/s00213-005-2212-8 | s2cid = 25147595 }}

In rats, imidazenil has been demonstrated to have low tolerance or dependence liability, unlike other benzodiazepine receptor agonist ligands, such as diazepam, bretazenil.{{cite journal | author = Auta J, Giusti P, Guidotti A, Costa E | title = Imidazenil, a partial positive allosteric modulator of GABAA receptors, exhibits low tolerance and dependence liabilities in the rat | journal = J Pharmacol Exp Ther | volume = 270 | issue = 3 | pages = 1262-9| date = September 1994| pmid = 7932179 | doi = }}