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.12
ELB-139 is a subtype-selective partial agonist at GABAA 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 humans6 The sponsor elbion AG registered a clinical trial in ClinicalTrials.gov for the treatment of anxiety associated with panic disorder but the results have not been reported.7 It was developed by Arzeitmittelwerk Dresden in the 1990s.8
- ^ Langen, B; Egerland, U; Bernöster, K; Dost, R; Unverferth, K; Rundfeldt, C (2005). "Characterization in rats of the anxiolytic potential of ELB139 1-(4-chlorophenyl)-4-piperidin-1-yl-1,5-dihydro-imidazol-2-on, a new agonist at the benzodiazepine binding site of the GABAA receptor". The Journal of Pharmacology and Experimental Therapeutics 314 (2): 717–24. doi:10.1124/jpet.105.084681. PMID 15860576.
- ^ Atack, JR (2005). "The benzodiazepine binding site of GABA(A) receptors as a target for the development of novel anxiolytics". Expert Opinion on Investigational Drugs 14 (5): 601–18. doi:10.1517/135437126.96.36.1991. PMID 15926867.
- ^ Rabe, H; Kronbach, C; Rundfeldt, C; Lüddens, H (2007). "The novel anxiolytic ELB139 displays selectivity to recombinant GABA(A) receptors different from diazepam". Neuropharmacology 52 (3): 796–801. doi:10.1016/j.neuropharm.2006.09.013. PMID 17087982.
- ^ Grunwald, C; Rundfeldt, C; Lankau, HJ; Arnold, T; Höfgen, N; Dost, R; Egerland, U; Hofmann, HJ et al. (2006). "Synthesis, pharmacology, and structure-activity relationships of novel imidazolones and pyrrolones as modulators of GABAA receptors". Journal of Medical Chemistry 49 (6): 1855–66. doi:10.1021/jm0509400. PMID 16539371.
- ^ Langen, B; Rundfeldt, C (2007). "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 Behavior 86 (1): 79–85. doi:10.1016/j.pbb.2006.12.010. PMID 17257662.
- ^ Rogawski, MA (2006). "Diverse mechanisms of antiepileptic drugs in the development pipeline". Epilepsy Res 69 (3): 273–294. doi:10.1016/j.eplepsyres.2006.02.004. PMC 1562526. PMID 16621450.
- ^ Whiting, PJ (2006). "GABA-A receptors: a viable target for novel anxiolytics?". Current Opinion in Pharmacology 6 (1): 24–9. doi:10.1016/j.coph.2005.08.005. PMID 16359919.
- ^ US Patent 5869481 Anticonvulsive 1-ar(alk)ylimidazolin-2-ones and process for making