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TPA023 [7-(1,1-dimethylethyl)-6-(2-ethyl-2H-1,2,4-triazol-3-ylmethoxy)-3-(2-fluorophenyl)-1,2,4-triazolo[4,3-b]pyridazine], an agonist selective for alpha2- and alpha3-containing GABAA receptors, is a nonsedating anxiolytic in rodents and primates.
Atack JR, Wafford KA, Tye SJ, Cook SM, Sohal B, Pike A, Sur C, Melillo D, Bristow L, Bromidge F, Ragan I, Kerby J, Street L, Carling R, Castro JL, Whiting P, Dawson GR, McKernan RM. Atack JR, et al. Among authors: whiting p. J Pharmacol Exp Ther. 2006 Jan;316(1):410-22. doi: 10.1124/jpet.105.089920. Epub 2005 Sep 23. J Pharmacol Exp Ther. 2006. PMID: 16183706
Evidence for a significant role of alpha 3-containing GABAA receptors in mediating the anxiolytic effects of benzodiazepines.
Dias R, Sheppard WF, Fradley RL, Garrett EM, Stanley JL, Tye SJ, Goodacre S, Lincoln RJ, Cook SM, Conley R, Hallett D, Humphries AC, Thompson SA, Wafford KA, Street LJ, Castro JL, Whiting PJ, Rosahl TW, Atack JR, McKernan RM, Dawson GR, Reynolds DS. Dias R, et al. J Neurosci. 2005 Nov 16;25(46):10682-8. doi: 10.1523/JNEUROSCI.1166-05.2005. J Neurosci. 2005. PMID: 16291941 Free PMC article.
Sedative but not anxiolytic properties of benzodiazepines are mediated by the GABA(A) receptor alpha1 subtype.
McKernan RM, Rosahl TW, Reynolds DS, Sur C, Wafford KA, Atack JR, Farrar S, Myers J, Cook G, Ferris P, Garrett L, Bristow L, Marshall G, Macaulay A, Brown N, Howell O, Moore KW, Carling RW, Street LJ, Castro JL, Ragan CI, Dawson GR, Whiting PJ. McKernan RM, et al. Among authors: whiting pj. Nat Neurosci. 2000 Jun;3(6):587-92. doi: 10.1038/75761. Nat Neurosci. 2000. PMID: 10816315
Sedation and anesthesia mediated by distinct GABA(A) receptor isoforms.
Reynolds DS, Rosahl TW, Cirone J, O'Meara GF, Haythornthwaite A, Newman RJ, Myers J, Sur C, Howell O, Rutter AR, Atack J, Macaulay AJ, Hadingham KL, Hutson PH, Belelli D, Lambert JJ, Dawson GR, McKernan R, Whiting PJ, Wafford KA. Reynolds DS, et al. J Neurosci. 2003 Sep 17;23(24):8608-17. doi: 10.1523/JNEUROSCI.23-24-08608.2003. J Neurosci. 2003. PMID: 13679430 Free PMC article.
681 results