ANA-12

In today's world, ANA-12 is a highly relevant topic that has captured the attention of millions of people around the world. With a significant impact on various aspects of daily life, ANA-12 has been the subject of debate and discussion in all spheres of society. From its impact on health and well-being, to its influence on economics and politics, ANA-12 has become a point of interest and concern for many. In this article, we will explore the phenomenon of ANA-12 in depth, analyzing its implications and consequences in different contexts. With a global perspective, we seek to shed light on this topic and provide a broader and more complete vision of its scope and importance in today's world.

ANA-12
Clinical data
ATC code
  • None
Identifiers
  • N-phenyl]-1-benzothiophene-2-carboxamide
CAS Number
PubChem CID
ChemSpider
UNII
CompTox Dashboard (EPA)
ECHA InfoCard100.229.925 Edit this at Wikidata
Chemical and physical data
FormulaC22H21N3O3S
Molar mass407.49 g·mol−1
3D model (JSmol)
  • C1CCNC(=O)C(C1)NC(=O)C2=CC=CC=C2NC(=O)C3=CC4=CC=CC=C4S3
  • InChI=1S/C22H21N3O3S/c26-20(25-17-10-5-6-12-23-21(17)27)15-8-2-3-9-16(15)24-22(28)19-13-14-7-1-4-11-18(14)29-19/h1-4,7-9,11,13,17H,5-6,10,12H2,(H,23,27)(H,24,28)(H,25,26)
  • Key:TUSCYCAIGRVBMD-UHFFFAOYSA-N

ANA-12 is a selective, small-molecule non-competitive antagonist of TrkB (Kd = 10 nM and 12 μM for the high- and low-affinity sites, respectively), the main receptor of brain-derived neurotrophic factor (BDNF). The compound crosses the blood-brain-barrier and exerts central TrkB blockade, producing effects as early as 30 minutes (~400 nM) and as long as 6 hours (~10 nM) following intraperitoneal injection in mice. It blocks the neurotrophic actions of BDNF without compromising neuron survival.

Research

ANA-12 produces rapid antidepressant- and anxiolytic-like effects in animal models, the former of which have been elucidated to be mediated by blockade of BDNF signaling in the nucleus accumbens. It has also been found to alleviate methamphetamine-induced depression-like behavior (including anhedonia), behavioral sensitization, and nucleus accumbens neuroplasticity changes with subchronic (14-day) administration in mice, whereas the TrkB agonist 7,8-dihydroxyflavone was ineffective in doing so.

ANA-12 blocks the cognitive-enhancing effects of environmental enrichment and calorie restriction in rodents, which are mediated by BDNF signaling through TrkB in the hippocampus. It also blocks hippocampal neurogenesis induced by physical exercise in rodents, and may block the cognitive-enhancing effects of exercise as well.

See also

References

  1. ^ a b c d Cazorla M, Prémont J, Mann A, Girard N, Kellendonk C, Rognan D (May 2011). "Identification of a low-molecular weight TrkB antagonist with anxiolytic and antidepressant activity in mice". The Journal of Clinical Investigation. 121 (5): 1846–1857. doi:10.1172/JCI43992. PMC 3083767. PMID 21505263.
  2. ^ Zhang JC, Wu J, Fujita Y, Yao W, Ren Q, Yang C, et al. (October 2014). "Antidepressant effects of TrkB ligands on depression-like behavior and dendritic changes in mice after inflammation". The International Journal of Neuropsychopharmacology. 18 (4): pyu077. doi:10.1093/ijnp/pyu077. PMC 4360225. PMID 25628381.
  3. ^ Shirayama Y, Yang C, Zhang JC, Ren Q, Yao W, Hashimoto K (December 2015). "Alterations in brain-derived neurotrophic factor (BDNF) and its precursor proBDNF in the brain regions of a learned helplessness rat model and the antidepressant effects of a TrkB agonist and antagonist". European Neuropsychopharmacology. 25 (12): 2449–2458. doi:10.1016/j.euroneuro.2015.09.002. PMID 26419294. S2CID 851.
  4. ^ Ren Q, Ma M, Yang C, Zhang JC, Yao W, Hashimoto K (October 2015). "BDNF-TrkB signaling in the nucleus accumbens shell of mice has key role in methamphetamine withdrawal symptoms". Translational Psychiatry. 5 (10): e666. doi:10.1038/tp.2015.157. PMC 4930133. PMID 26506052.
  5. ^ Fan D, Li J, Zheng B, Hua L, Zuo Z (January 2016). "Enriched Environment Attenuates Surgery-Induced Impairment of Learning, Memory, and Neurogenesis Possibly by Preserving BDNF Expression". Molecular Neurobiology. 53 (1): 344–354. doi:10.1007/s12035-014-9013-1. PMID 25432890. S2CID 15795328.
  6. ^ Kishi T, Hirooka Y, Nagayama T, Isegawa K, Katsuki M, Takesue K, Sunagawa K (2015). "Calorie restriction improves cognitive decline via up-regulation of brain-derived neurotrophic factor: tropomyosin-related kinase B in hippocampus ofobesity-induced hypertensive rats". International Heart Journal. 56 (1): 110–115. doi:10.1536/ihj.14-168. PMID 25503654.
  7. ^ Ambrogini P, Lattanzi D, Ciuffoli S, Betti M, Fanelli M, Cuppini R (October 2013). "Physical exercise and environment exploration affect synaptogenesis in adult-generated neurons in the rat dentate gyrus: possible role of BDNF". Brain Research. 1534: 1–12. doi:10.1016/j.brainres.2013.08.023. hdl:11576/2575580. PMID 23973748. S2CID 35405574.
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