同义名 :	RG1662; RO5186582
	CAS号 :	1159600-41-5
	货号 :	A106679
	分子式 :	C21H20FN3O5S
	纯度 :	99%+
	分子量 :	445.46
	MDL号 :	MFCD28902245
	存储条件：	Pure form Sealed in dry,2-8°C In solvent -20°C:3-6个月-80°C:12个月
	溶解度 :	-
	动物实验配方：

生物活性

描述

GABA (γ-aminobutyric acid) receptors, of which there are two types, are involved in inhibitory synapses within the central nervous system. The GABAA receptor (GABAAR) has a central role in modern anesthesia and sedation practice, which is evident from the high proportion of agents that target the GABAAR[3]. MK-0343 binds to α1-, α2-, α3- and α5-containing human recombinant GABAA receptors with comparable high affinity (0.21-0.40 nM)[4]. This compound readily penetrates the brain in rats and occupies the benzodiazepine site of GABAA receptors, with an Occ50 of 2.2 mg/kg p.o. and a corresponding plasma EC50 of 115 ng/mL[4]. MK-0343 causes sedation in humans at a dose of 2 mg, corresponding to levels of occupancy considerably less than those predicted from rodent models to be required for anxiolytic efficacy (∼35-65%)[4]. MK-0343 0.75 mg was equipotent with lorazepam as indicated by saccadic peak velocity (SPV) (-42.4 deg/s), saccadic latency (0.02 s) and Visual Analogue scales (VAS) alertness scores (1.50 ln mm), while effects on memory and postural stability were smaller[5].

实验方案
	1mg	5mg	10mg
1 mM 5 mM 10 mM	2.24mL 0.45mL 0.22mL	11.22mL 2.24mL 1.12mL	22.45mL 4.49mL 2.24mL

参考文献

[1]Myers JF, Comley RA, Gunn RN. Quantification of [(11)C] Ro15-4513 GABA(A)α5 specific binding and regional selectivity in humans. J Cereb Blood Flow Metab. 2017 Jun;37(6):2137-2148. [2]Liogier d'Ardhuy X, et al. Assessment of Cognitive Scales to Examine Memory, Executive Function and Language in Individuals with Down Syndrome: Implications of a 6-month Observational Study. Front Behav Neurosci. 2015 Nov 18;9:300. [3]Brohan J, Goudra BG. The Role of GABA Receptor Agonists in Anesthesia and Sedation. CNS Drugs. 2017 Oct;31(10):845-856. doi: 10.1007/s40263-017-0463-7. PMID: 29039138. [4]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. MRK-409 (MK-0343), a GABAA receptor subtype-selective partial agonist, is a non-sedating anxiolytic in preclinical species but causes sedation in humans. J Psychopharmacol. 2011 Mar;25(3):314-28. doi: 10.1177/0269881109354927. Epub 2010 Feb 10. PMID: 20147571. [5]de Haas SL, de Visser SJ, van der Post JP, Schoemaker RC, van Dyck K, Murphy MG, de Smet M, Vessey LK, Ramakrishnan R, Xue L, Cohen AF, van Gerven JM. Pharmacodynamic and pharmacokinetic effects of MK-0343, a GABA(A) alpha2,3 subtype selective agonist, compared to lorazepam and placebo in healthy male volunteers. J Psychopharmacol. 2008 Jan;22(1):24-32. doi: 10.1177/0269881107082108. PMID: 18187530.