Cutamesine (SA 4503) is a synthetic sigma receptor agonist which is selective for the
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Names | |
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Preferred IUPAC name
1-[2-(3,4-Dimethoxyphenyl)ethyl]-4-(3-phenylpropyl)piperazine | |
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3D model (JSmol)
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PubChem CID
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CompTox Dashboard (EPA)
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Properties | |
C23H32N2O2 | |
Molar mass | 368.521 g·mol−1 |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Structure
editThe molecular formula for cutamesine is C23H32N2O2.[2] This particular agonist is a piperazine, meaning that its core functional group is a six-membered heterocycle with two oppositely-placed nitrogen atoms. Two phenalkyl groups act as substituents for the two nitrogen atoms. The phenethyl group has methoxy groups on the 3 and 4 locations of the aromatic ring, while the phenpropyl group has no additional functional groups attached.
Affinity
editCauses of Affinity
editThe 3,4-methoxy groups located on the phenethyl group play an important role in
Binding Trends
editCutamesine exhibits high binding affinity for the
Physiological Effects
editMemory and Amnesia
editIt has been shown that cutamesine has anti-amnesic properties and could be used to reduce the effects of amnesia caused by REM sleep deprivation.[12] Decreases in the memory function of rats caused by the presence of scopolamine has been shown to be mitigated by the introduction of SA 4503.[13] The activation of the MAPK/ERK (mitogen-activated protein kinase/extracellular signal-regulated kinase) pathway in neurons is repressed by SA 4503, which in turn leads to reduced stress-related cell death.[6] The presence of SA 4503 has a positive impact on the number of active dopaminergic neurons in the frontal cortex, which is linked to improved memory function.[5]
Depression
editHeart
editThe administration of cutamesine has been shown to mitigate the effects of cardiac hypertrophy.[15] Angiotensin II-induced hypertrophy results in lower ATP production and smaller mitochondrial size in cardiomyocytes, and introduction of SA 4503 returns both ATP production and mitochondrial size to baseline.[15]
Hearing
editThe presence of cutamesine is positively correlated with the presence of hippocampal brain‐derived neurotrophic factor (BDNF).[16] Due to the relationship between the presence of BDNF and ciliary neurotrophic factor and the preservation of auditory nerves, it is thought that cutamesine may have a positive effect on the health of the cochlea.[16] Despite the apparent auditory benefits of cutamesine treatment, it does not prevent hearing loss that is a result of aging.[16]
References
edit- ^ a b c d e Skuza, Grazyna (November 2003). "Potential antidepressant activity of sigma ligands". Polish Journal of Pharmacology. 55 (6): 923–934. ISSN 1230-6002. PMID 14730086.
- ^ a b "cutamesine | C23H32N2O2 | ChemSpider". www.chemspider.com. Retrieved 2019-06-12.
- ^ a b c Hayashi, Teruo; Su, Tsung-Ping (November 2007). "Sigma-1 Receptor Chaperones at the ER- Mitochondrion Interface Regulate Ca2+ Signaling and Cell Survival". Cell. 131 (3): 596–610. doi:10.1016/j.cell.2007.08.036. PMID 17981125. S2CID 18885068.
- ^ a b Weissman, A. D.; Su, T. P.; Hedreen, J. C.; London, E. D. (October 1988). "Sigma receptors in post-mortem human brains". The Journal of Pharmacology and Experimental Therapeutics. 247 (1): 29–33. ISSN 0022-3565. PMID 2845055.
- ^ a b Skuza, G.; Wedzony, K. (November 2004). "Behavioral Pharmacology of
σ -Ligands". Pharmacopsychiatry. 37 (S 3): 183–188. doi:10.1055/s-2004-832676. ISSN 0176-3679. PMID 15547784. S2CID 87032896. - ^ a b Tuerxun, Tuerhong; Numakawa, Tadahiro; Adachi, Naoki; Kumamaru, Emi; Kitazawa, Hiromi; Kudo, Motoshige; Kunugi, Hiroshi (January 2010). "SA4503, a sigma-1 receptor agonist, prevents cultured cortical neurons from oxidative stress-induced cell death via suppression of MAPK pathway activation and glutamate receptor expression". Neuroscience Letters. 469 (3): 303–308. doi:10.1016/j.neulet.2009.12.013. PMID 20025928. S2CID 20552121.
- ^ a b Xu, Rong; Lord, Sarah A.; Peterson, Ryan M.; Fergason-Cantrell, Emily A.; Lever, John R.; Lever, Susan Z. (January 2015). "Ether modifications to 1-[2-(3,4-dimethoxyphenyl)ethyl]-4-(3-phenylpropyl)piperazine (SA4503): Effects on binding affinity and selectivity for sigma receptors and monoamine transporters". Bioorganic & Medicinal Chemistry. 23 (1): 222–230. doi:10.1016/j.bmc.2014.11.007. PMC 4274187. PMID 25468036.
- ^ a b Ablordeppey, Seth Y; Fischer, James B; Glennon, Richard A (August 2000). "Is a Nitrogen Atom an Important Pharmacophoric Element in Sigma Ligand Binding?". Bioorganic & Medicinal Chemistry. 8 (8): 2105–2111. doi:10.1016/S0968-0896(00)00148-6. PMID 11003156.
- ^ a b c Matsuno, Kiyoshi; Nakazawa, Minako; Okamoto, Kazuyoshi; Kawashima, Yoichi; Mita, Shiro (June 1996). "Binding properties of SA4503, a novel and selective
σ 1 receptor agonist". European Journal of Pharmacology. 306 (1–3): 271–279. doi:10.1016/0014-2999(96)00201-4. PMID 8813641. - ^ Horan, Bryan; Gifford, Andrew N.; Matsuno, Kiyoshi; Mita, Shiro; Ashby, Charles R. (October 2002). "Effect of SA4503 on the electrically evoked release of3H-acetylcholine from striatal and hippocampal rat brain slices". Synapse. 46 (1): 1–3. doi:10.1002/syn.10107. ISSN 0887-4476. PMID 12211092. S2CID 41458292.
- ^ a b Toyohara, Jun; Sakata, Muneyuki; Ishiwata, Kiichi (October 2012). "Re-evaluation of in vivo selectivity of [11C]SA4503 to
σ 1 receptors in the brain: Contributions of emopamil binding protein". Nuclear Medicine and Biology. 39 (7): 1049–1052. doi:10.1016/j.nucmedbio.2012.03.002. PMID 22497960. - ^ Ramakrishnan, Nisha K.; Schepers, Marianne; Luurtsema, Gert; Nyakas, Csaba J.; Elsinga, Philip H.; Ishiwata, Kiichi; Dierckx, Rudi A. J. O.; van Waarde, Aren (June 2015). "Cutamesine Overcomes REM Sleep Deprivation-Induced Memory Loss: Relationship to Sigma-1 Receptor Occupancy". Molecular Imaging and Biology. 17 (3): 364–372. doi:10.1007/s11307-014-0808-2. ISSN 1536-1632. PMID 25449772. S2CID 826030.
- ^ Matsuno, Kiyoshi; Senda, Toshihiko; Kobayashi, Tetsuya; Okamoto, Kazuyoshi; Nakata, Katsuhiko; Mita, Shiro (February 1997). "SA4503, a novel cognitive enhancer, with
σ 1 receptor agonistic properties". Behavioural Brain Research. 83 (1–2): 221–224. doi:10.1016/S0166-4328(97)86074-3. PMID 9062689. S2CID 54240821. - ^ Rogóż, Zofia; Skuza, Grażyna; Maj, Jerzy; Danysz, Wojciech (June 2002). "Synergistic effect of uncompetitive NMDA receptor antagonists and antidepressant drugs in the forced swimming test in rats". Neuropharmacology. 42 (8): 1024–1030. doi:10.1016/S0028-3908(02)00055-2. PMID 12128003. S2CID 20376278.
- ^ a b Hirano, Kohga; Tagashira, Hideaki; Fukunaga, Kohji (2014). "Cardioprotective Effect of the Selective Sigma-1 Receptor Agonist, SA4503". Yakugaku Zasshi. 134 (6): 707–713. doi:10.1248/yakushi.13-00255-3. ISSN 0031-6903. PMID 24882645.
- ^ a b c Yamashita, Daisuke; Sun, Guang-wei; Cui, Yong; Mita, Shiro; Otsuki, Naoki; Kanzaki, Sho; Nibu, Ken-ichi; Ogawa, Kaoru; Matsunaga, Tatsuo (May 2015). "Neuroprotective effects of cutamesine, a ligand of the sigma-1 receptor chaperone, against noise-induced hearing loss: Cutamesine Protects Against Hearing Loss". Journal of Neuroscience Research. 93 (5): 788–795. doi:10.1002/jnr.23543. PMID 25612541. S2CID 206130476.
External links
edit- SA+4503 at the U.S. National Library of Medicine Medical Subject Headings (MeSH)