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MRK-409 (MK-0343), a GABAA receptor subtype-selective partial agonist, is a non-sedating anxiolytic in preclinical species but causes sedation in humans.
Atack JR, Wafford KA, Street LJ, Dawson GR, Tye S, Van Laere K, Bormans G, Sanabria-Bohórquez SM, De Lepeleire I, de Hoon JN, Van Hecken A, Burns HD, McKernan RM, Murphy MG, Hargreaves RJ. Atack JR, et al. Among authors: dawson gr. J Psychopharmacol. 2011 Mar;25(3):314-28. doi: 10.1177/0269881109354927. Epub 2010 Feb 10. J Psychopharmacol. 2011. PMID: 20147571 Clinical Trial.
Preclinical and clinical pharmacology of TPA023B, a GABAA receptor α2/α3 subtype-selective partial agonist.
Atack JR, Hallett DJ, Tye S, Wafford KA, Ryan C, Sanabria-Bohórquez SM, Eng WS, Gibson RE, Burns HD, Dawson GR, Carling RW, Street LJ, Pike A, De Lepeleire I, Van Laere K, Bormans G, de Hoon JN, Van Hecken A, McKernan RM, Murphy MG, Hargreaves RJ. Atack JR, et al. Among authors: dawson gr. J Psychopharmacol. 2011 Mar;25(3):329-44. doi: 10.1177/0269881109354928. Epub 2010 Feb 15. J Psychopharmacol. 2011. PMID: 20156926 Clinical Trial.
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: dawson gr. Nat Neurosci. 2000 Jun;3(6):587-92. doi: 10.1038/75761. Nat Neurosci. 2000. PMID: 10816315
Loss of the major GABA(A) receptor subtype in the brain is not lethal in mice.
Sur C, Wafford KA, Reynolds DS, Hadingham KL, Bromidge F, Macaulay A, Collinson N, O'Meara G, Howell O, Newman R, Myers J, Atack JR, Dawson GR, McKernan RM, Whiting PJ, Rosahl TW. Sur C, et al. Among authors: dawson gr. J Neurosci. 2001 May 15;21(10):3409-18. doi: 10.1523/JNEUROSCI.21-10-03409.2001. J Neurosci. 2001. PMID: 11331371 Free PMC article.
An inverse agonist selective for alpha5 subunit-containing GABAA receptors enhances cognition.
Dawson GR, Maubach KA, Collinson N, Cobain M, Everitt BJ, MacLeod AM, Choudhury HI, McDonald LM, Pillai G, Rycroft W, Smith AJ, Sternfeld F, Tattersall FD, Wafford KA, Reynolds DS, Seabrook GR, Atack JR. Dawson GR, et al. J Pharmacol Exp Ther. 2006 Mar;316(3):1335-45. doi: 10.1124/jpet.105.092320. Epub 2005 Dec 2. J Pharmacol Exp Ther. 2006. PMID: 16326923
Occupancy of human brain GABA(A) receptors by the novel α5 subtype-selective benzodiazepine site inverse agonist α5IA as measured using [¹¹C]flumazenil PET imaging.
Eng W, Atack JR, Bergstrom M, Sanabria S, Appel L, Dawson GR, Sciberras D, Hargreaves RJ, Langstrom B, Burns HD. Eng W, et al. Among authors: dawson gr. Neuropharmacology. 2010 Dec;59(7-8):635-9. doi: 10.1016/j.neuropharm.2010.07.024. Epub 2010 Aug 7. Neuropharmacology. 2010. PMID: 20696179
148 results