Imidazenil

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


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CAS_number = 151271-08-8
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PubChem = 119194
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C = 18 | H = 12 | Br = 1 | F = 1 | N = 4 | O = 1
molecular_weight = 399.216 g/mol
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Imidazenil is an 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 GABA_A partial agonist [Griebel G, Sanger DJ, Perrault G. Further evidence for differences between non-selective and BZ-1 (omega 1) selective, benzodiazepine receptor ligands in murine models of "state" and "trait" anxiety. "Neuropharmacology". 1996;35(8):1081-91.] 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 [Giusti P, Ducic I, Puia G, Arban R, Walser A, Guidotti A, Costa E. Imidazenil: a new partial positive allosteric modulator of gamma-aminobutyric acid (GABA) action at GABAA receptors. "Journal of Pharmacology and Experimental Therapeutics". 1993 Aug;266(2):1018-28.] or amnestic [Auta J, Faust WB, Lambert P, Guidotti A, Costa E, Moerschbaecher JM. Comparison of the effects of full and partial allosteric modulators of GABA(A) receptors on complex behavioral processes in monkeys. "Behavioural Pharmacology". 1995 Jun;6(4):323-332.] effects. In fact, imidazenil blocks the sedative effects of diazepam, yet without lowering the convulsion threshold, [Auta J, Costa E, Davis JM, Guidotti A. Imidazenil: an antagonist of the sedative but not the anticonvulsant action of diazepam. "Neuropharmacology". 2005 Sep;49(3):425-9.] and so potentially could be a more flexible antidote than the antagonist flumazenil which is commonly used to treat benzodiazepine overdose at present.

This unusual profile of effects makes imidazenil potentially a very useful drug. In animal studies it has been shown to be an effective anxiolytic and strong anticonvulsant, yet without many of the side effects associated with other benzodiazepines; it does not produce tolerance [Ghiani CA, Serra M, Motzo C, Giusti P, Cuccheddu T, Porceddu ML, Biggio G. Chronic administration of an anticonvulsant dose of imidazenil fails to induce tolerance of GABAA receptor function in mice. "European Journal of Pharmacology". 1994 Mar 21;254(3):299-302.] or dependence, [Auta J, Giusti P, Guidotti A, Costa E. Imidazenil, a partial positive allosteric modulator of GABAA receptors, exhibits low tolerance and dependence liabilities in the rat. "Journal of Pharmacology and Experimental Therapeutics". 1994 Sep;270(3):1262-9.] reverses the amnestic effects of conventional benzodiazepines, and does not potentiate the effects of alcohol. [Thompson DM, Auta J, Guidotti A, Costa E. Imidazenil, a new anxiolytic and anticonvulsant drug, attenuates a benzodiazepine-induced cognition deficit in monkeys. "Journal of Pharmacology and Experimental Therapeutics". 1995 Jun;273(3):1307-12.] [Auta J, Guidotti A, Costa E. Imidazenil prevention of alprazolam-induced acquisition deficit in patas monkeys is devoid of tolerance. "Proceedings of the National Academy of Sciences U S A". 2000 Feb 29;97(5):2314-9.]

Imidazenil has not yet been developed commercially for use in humans, however it has been suggested as a safe and effective treatment for anxiety, [Atack JR. Anxioselective compounds acting at the GABA(A) receptor benzodiazepine binding site. "Current Drug Targets. CNS and Neurological Disorders". 2003 Aug;2(4):213-32.] a potent yet non-sedating anticonvulsant which might be particularly useful in the treatment of poisoning with organophosphate nerve agents, [Rump S, Gidynska T, Galecka E, Antkowiak O, Nawrocka M, Kowalczyk M. Effects of imidazenil, a new benzodiazepine receptor partial agonist, in the treatment of convulsions in organophosphate intoxications. "Neurotoxicity Research". 2000;2(1):17-22.] [Auta J, Costa E, Davis J, Guidotti A. Imidazenil: a potent and safe protective agent against diisopropyl fluorophosphate toxicity. "Neuropharmacology". 2004 Mar;46(3):397-403.] and as a novel treatment for schizophrenia. [Guidotti A, Auta J, Davis JM, Dong E, Grayson DR, Veldic M, Zhang X, Costa E. GABAergic dysfunction in schizophrenia: new treatment strategies on the horizon. "Psychopharmacology (Berlin)". 2005 Jul;180(2):191-205.]

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