Difference between revisions of "ELB-139"

Latest revision as of 10:09, 20 September 2010

ELB-139 (LS-191,811) is an anxiolytic drug with a novel chemical structure, which is used in scientific research. It has similar effects to benzodiazepine drugs, but is structurally distinct and so is classed as a nonbenzodiazepine anxiolytic.^[1][2]

ELB-139 is a subtype-selective partial agonist at GABA_A receptors, with highest affinity for the α3 subtype, but highest efficacy at α1 and α2.^[3] It has primarily anxiolytic and anticonvulsant effects, but produces little sedative effects or ataxia,^[4] and has also been demonstrated in rats to increase serotonin levels in the striatum and prefrontal cortex, without affecting dopamine levels.^[5] It has been proposed as a possible candidate for a novel non-sedating anxiolytic or anticonvulsant drug for use in humans, but no trials beyond laboratory work in animals have been conducted to date.^[6]

References

1. ↑ Characterization in rats of the anxiolytic potential of ELB139 [1-(4-chlorophenyl)-4-piperidin-1-yl-1,5-dihydro-imidazol-2-one], a new agonist at the benzodiazepine binding site of the GABAA receptor. Journal of Pharmacology and Experimental Therapeutics. 2005 Aug;314(2):717-24. PMID 15860576
2. ↑ Atack JR. The benzodiazepine binding site of GABA(A) receptors as a target for the development of novel anxiolytics. Expert Opinion in Investigational Drugs. 2005 May;14(5):601-18. PMID 15926867
3. ↑ Rabe H, Kronbach C, Rundfeldt C, Lüddens H. The novel anxiolytic ELB139 displays selectivity to recombinant GABA(A) receptors different from diazepam. Neuropharmacology. 2007 Mar;52(3):796-801. PMID 17087982
4. ↑ Grunwald C, Rundfeldt C, Lankau HJ, Arnold T, Höfgen N, Dost R, Egerland U, Hofmann HJ, Unverferth K. Synthesis, pharmacology, and structure-activity relationships of novel imidazolones and pyrrolones as modulators of GABAA receptors. Journal of Medicinal Chemistry. 2006 Mar 23;49(6):1855-66. PMID 16539371
5. ↑ Langen B, Rundfeldt C. ELB139 an agonist at the benzodiazepine binding site increases 5-HT in the striatum and prefrontal cortex of rats: a microdialysis study. Pharmacology, Biochemistry and Behaviour. 2007 Jan;86(1):79-85. PMID 17257662
6. ↑ Whiting PJ. GABA-A receptors: a viable target for novel anxiolytics? Current Opinion in Pharmacology. 2006 Feb;6(1):24-9. PMID 16359919