|Chemical and physical data|
|Molar mass||407.485 g/mol g·mol−1|
|3D model (JSmol)|
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.
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.
- Cazorla, Maxime; Prémont, Joël; Mann, Andre; Girard, Nicolas; Kellendonk, Christoph; Rognan, Didier (2011). "Identification of a low–molecular weight TrkB antagonist with anxiolytic and antidepressant activity in mice". Journal of Clinical Investigation. 121 (5): 1846–1857. doi:10.1172/JCI43992. ISSN 0021-9738. PMC 3083767. PMID 21505263.
- Zhang JC, Wu J, Fujita Y, Yao W, Ren Q, Yang C, Li SX, Shirayama Y, Hashimoto K (2015). "Antidepressant effects of TrkB ligands on depression-like behavior and dendritic changes in mice after inflammation". Int. J. Neuropsychopharmacol. 18 (4): pyu077. doi:10.1093/ijnp/pyu077. PMC 4360225. PMID 25628381.
- Shirayama Y, Yang C, Zhang JC, Ren Q, Yao W, Hashimoto K (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". Eur Neuropsychopharmacol. 25 (12): 2449–58. doi:10.1016/j.euroneuro.2015.09.002. PMID 26419294.
- Ren Q, Ma M, Yang C, Zhang JC, Yao W, Hashimoto K (2015). "BDNF-TrkB signaling in the nucleus accumbens shell of mice has key role in methamphetamine withdrawal symptoms". Transl Psychiatry. 5 (10): e666. doi:10.1038/tp.2015.157. PMC 4930133. PMID 26506052.
- Fan D, Li J, Zheng B, Hua L, Zuo Z (2016). "Enriched Environment Attenuates Surgery-Induced Impairment of Learning, Memory, and Neurogenesis Possibly by Preserving BDNF Expression". Mol. Neurobiol. 53 (1): 344–54. doi:10.1007/s12035-014-9013-1. PMID 25432890.
- 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 of obesity-induced hypertensive rats". Int Heart J. 56 (1): 110–5. doi:10.1536/ihj.14-168. PMID 25503654.
- Ambrogini, P.; Lattanzi, D.; Ciuffoli, S.; Betti, M.; Fanelli, M.; Cuppini, R. (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. ISSN 0006-8993. PMID 23973748.
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