WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H526626
CAS#: 252977-51-8
Description: TPA023, also known as MK 0777, is an anxiolytic agent and a subtype-selective, mixed agonist-antagonist at GABAA receptors, which acts as a partial agonist at the α2 and α3 subtypes, but as a silent antagonist at α1 and α5 subtypes. It has primarily anxiolytic and anticonvulsant effects in animal tests, but with no sedative effects even at 50× the effective anxiolytic dose. In human trials on healthy volunteers, TPA-023 was comparable to lorazepam, but had much less side effects on cognition, memory, alertness or coordination.
Hodoodo Cat#: H526626
Name: TPA023
CAS#: 252977-51-8
Chemical Formula: C20H22FN7O
Exact Mass: 395.19
Molecular Weight: 395.442
Elemental Analysis: C, 60.75; H, 5.61; F, 4.80; N, 24.79; O, 4.05
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Synonym: TPA023; TPA-023; TPA 023; MK0777; MK 0777; MK-0777; L830982; L-830982; L 830982
IUPAC/Chemical Name: 7-(tert-butyl)-6-((1-ethyl-1H-1,2,4-triazol-5-yl)methoxy)-3-(2-fluorophenyl)-[1,2,4]triazolo[4,3-b]pyridazine
InChi Key: QKIWQBLNTSQOLY-UHFFFAOYSA-N
InChi Code: InChI=1S/C20H22FN7O/c1-5-27-17(22-12-23-27)11-29-19-14(20(2,3)4)10-16-24-25-18(28(16)26-19)13-8-6-7-9-15(13)21/h6-10,12H,5,11H2,1-4H3
SMILES Code: FC1=CC=CC=C1C2=NN=C3C=C(C(C)(C)C)C(OCC4=NC=NN4CC)=NN32
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
More Info:
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The following data is based on the product molecular weight 395.44 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | |
| In vitro protocol: | |
| In vivo protocol: |
1: Wang M, Li Y, Lin Y. GABAA receptor α2 subtype activation suppresses retinal spreading depression. Neuroscience. 2015 Jul 9;298:137-44. doi: 10.1016/j.neuroscience.2015.04.016. Epub 2015 Apr 18. PubMed PMID: 25896802.
2: de Lucas AG, Ahring PK, Larsen JS, Rivera-Arconada I, Lopez-Garcia JA, Mirza NR, Munro G. GABAA α5 subunit-containing receptors do not contribute to reversal of inflammatory-induced spinal sensitization as indicated by the unique selectivity profile of the GABAA receptor allosteric modulator NS16085. Biochem Pharmacol. 2015 Feb 1;93(3):370-9. doi: 10.1016/j.bcp.2014.12.010. Epub 2014 Dec 25. PubMed PMID: 25542996.
3: McEown K, Treit D. Α2 GABAA receptor sub-units in the ventral hippocampus and α5 GABAA receptor sub-units in the dorsal hippocampus mediate anxiety and fear memory. Neuroscience. 2013 Nov 12;252:169-77. doi: 10.1016/j.neuroscience.2013.08.012. Epub 2013 Aug 17. PubMed PMID: 23962649.
4: Soto PL, Ator NA, Rallapalli SK, Biawat P, Clayton T, Cook JM, Weed MR. Allosteric modulation of GABA(A) receptor subtypes:effects on visual recognition and visuospatial working memory in rhesus monkeys [corrected]. Neuropsychopharmacology. 2013 Oct;38(11):2315-25. doi: 10.1038/npp.2013.137. Epub 2013 May 31. Erratum in: Neuropsychopharmacology. 2013 Nov;38(12):2553. PubMed PMID: 23722241; PubMed Central PMCID: PMC3773684.
5: Munro G, Hansen RR, Mirza NR. GABA(A) receptor modulation: potential to deliver novel pain medicines? Eur J Pharmacol. 2013 Sep 15;716(1-3):17-23. doi: 10.1016/j.ejphar.2013.01.070. Epub 2013 Mar 13. Review. PubMed PMID: 23500203.
6: Hansen RR, Erichsen HK, Brown DT, Mirza NR, Munro G. Positive allosteric modulation of GABA-A receptors reduces capsaicin-induced primary and secondary hypersensitivity in rats. Neuropharmacology. 2012 Dec;63(8):1360-7. doi: 10.1016/j.neuropharm.2012.08.002. Epub 2012 Aug 17. PubMed PMID: 22985969.
7: Skolnick P. Anxioselective anxiolytics: on a quest for the Holy Grail. Trends Pharmacol Sci. 2012 Nov;33(11):611-20. doi: 10.1016/j.tips.2012.08.003. Epub 2012 Sep 14. Review. PubMed PMID: 22981367; PubMed Central PMCID: PMC3482271.
8: Engin E, Liu J, Rudolph U. α2-containing GABA(A) receptors: a target for the development of novel treatment strategies for CNS disorders. Pharmacol Ther. 2012 Nov;136(2):142-52. doi: 10.1016/j.pharmthera.2012.08.006. Epub 2012 Aug 18. Review. PubMed PMID: 22921455; PubMed Central PMCID: PMC3478960.
9: Vinkers CH, van Oorschot R, Nielsen EØ, Cook JM, Hansen HH, Groenink L, Olivier B, Mirza NR. GABA(A) receptor α subunits differentially contribute to diazepam tolerance after chronic treatment. PLoS One. 2012;7(8):e43054. doi: 10.1371/journal.pone.0043054. Epub 2012 Aug 13. PubMed PMID: 22912786; PubMed Central PMCID: PMC3418228.
10: Chen X, de Haas S, de Kam M, van Gerven J. An Overview of the CNS-Pharmacodynamic Profiles of Nonselective and Selective GABA Agonists. Adv Pharmacol Sci. 2012;2012:134523. doi: 10.1155/2012/134523. Epub 2012 Jan 29. PubMed PMID: 22363345; PubMed Central PMCID: PMC3273701.
11: Nickolls S, Mace H, Fish R, Edye M, Gurrell R, Ivarsson M, Pitcher T, Tanimoto-Mori S, Richardson D, Sweatman C, Nicholson J, Ward C, Jinks J, Bell C, Young K, Rees H, Moss A, Kinloch R, McMurray G. A Comparison of the α2/3/5 Selective Positive Allosteric Modulators L-838,417 and TPA023 in Preclinical Models of Inflammatory and Neuropathic Pain. Adv Pharmacol Sci. 2011;2011:608912. doi: 10.1155/2011/608912. Epub 2011 Nov 28. PubMed PMID: 22162674; PubMed Central PMCID: PMC3226534.
12: de Haas SL, Zoethout RW, Van Dyck K, De Smet M, Rosen LB, Murphy MG, Gottesdiener KM, Schoemaker RC, Cohen AF, van Gerven JM. The effects of TPA023, a GABAAα2,3 subtype-selective partial agonist, on essential tremor in comparison to alcohol. J Psychopharmacol. 2012 Feb;26(2):282-91. doi: 10.1177/0269881111415731. Epub 2011 Sep 2. PubMed PMID: 21890585.
13: Möhler H. The GABA system in anxiety and depression and its therapeutic potential. Neuropharmacology. 2012 Jan;62(1):42-53. doi: 10.1016/j.neuropharm.2011.08.040. Epub 2011 Sep 1. Review. PubMed PMID: 21889518.
14: Vinkers CH, Olivier B, Hanania T, Min W, Schreiber R, Hopkins SC, Campbell U, Paterson N. Discriminative stimulus properties of GABAA receptor positive allosteric modulators TPA023, ocinaplon and NG2-73 in rats trained to discriminate chlordiazepoxide or zolpidem. Eur J Pharmacol. 2011 Oct 1;668(1-2):190-3. doi: 10.1016/j.ejphar.2011.06.054. Epub 2011 Jul 8. PubMed PMID: 21762686.
15: Munro G, Erichsen HK, Rae MG, Mirza NR. A question of balance--positive versus negative allosteric modulation of GABA(A) receptor subtypes as a driver of analgesic efficacy in rat models of inflammatory and neuropathic pain. Neuropharmacology. 2011 Jul-Aug;61(1-2):121-32. doi: 10.1016/j.neuropharm.2011.03.017. Epub 2011 Mar 31. PubMed PMID: 21439986.
16: Atack JR. GABAA receptor alpha2/alpha3 subtype-selective modulators as potential nonsedating anxiolytics. Curr Top Behav Neurosci. 2010;2:331-60. Review. PubMed PMID: 21309116.
17: Buchanan RW, Keefe RS, Lieberman JA, Barch DM, Csernansky JG, Goff DC, Gold JM, Green MF, Jarskog LF, Javitt DC, Kimhy D, Kraus MS, McEvoy JP, Mesholam-Gately RI, Seidman LJ, Ball MP, McMahon RP, Kern RS, Robinson J, Marder SR. A randomized clinical trial of MK-0777 for the treatment of cognitive impairments in people with schizophrenia. Biol Psychiatry. 2011 Mar 1;69(5):442-9. doi: 10.1016/j.biopsych.2010.09.052. Epub 2010 Dec 8. PubMed PMID: 21145041; PubMed Central PMCID: PMC3058394.
18: Atack JR. GABAA receptor subtype-selective modulators. I. α2/α3-selective agonists as non-sedating anxiolytics. Curr Top Med Chem. 2011;11(9):1176-202. Review. PubMed PMID: 21050172.
19: Castner SA, Arriza JL, Roberts JC, Mrzljak L, Christian EP, Williams GV. Reversal of ketamine-induced working memory impairments by the GABAAalpha2/3 agonist TPA023. Biol Psychiatry. 2010 May 15;67(10):998-1001. doi: 10.1016/j.biopsych.2010.01.001. Epub 2010 Feb 26. PubMed PMID: 20189164.
20: Ator NA, Atack JR, Hargreaves RJ, Burns HD, Dawson GR. Reducing abuse liability of GABAA/benzodiazepine ligands via selective partial agonist efficacy at alpha1 and alpha2/3 subtypes. J Pharmacol Exp Ther. 2010 Jan;332(1):4-16. doi: 10.1124/jpet.109.158303. Epub 2009 Sep 29. PubMed PMID: 19789360; PubMed Central PMCID: PMC2802472.
