Siramesine (or Lu 28-179) is a sigma receptor agonist, selective for the σ2 subtype.[1] In animal studies, siramesine has been shown to produce anxiolytic[2] and antidepressant[3] effects. It was developed by the pharmaceutical company H Lundbeck for the treatment of anxiety,[4] although development was discontinued after clinical trials showed a lack of efficacy in humans. Siramesine has been shown to produce an enhanced antidepressant effect when co-administered with NMDA antagonists.[5] It has also been used to study the σ2 activity of cocaine,[6] and has been shown to produce anticancer properties both in vitro[7] and in vivo.[8]
References
- ^ Søby KK, Mikkelsen JD, Meier E, Thomsen C (July 2002). "Lu 28-179 labels a sigma(2)-site in rat and human brain". Neuropharmacology. 43 (1): 95–100. doi:10.1016/s0028-3908(02)00071-0. PMID 12213263. S2CID 140206932.
- ^ Sánchez C, Arnt J, Costall B, Kelly ME, Meier E, Naylor RJ, Perregaard J (December 1997). "The selective sigma2-ligand Lu 28-179 has potent anxiolytic-like effects in rodents". The Journal of Pharmacology and Experimental Therapeutics. 283 (3): 1323–32. PMID 9400007.
- ^ Sánchez C, Papp M (April 2000). "The selective sigma2 ligand Lu 28-179 has an antidepressant-like profile in the rat chronic mild stress model of depression". Behavioural Pharmacology. 11 (2): 117–24. doi:10.1097/00008877-200004000-00003. PMID 10877116. S2CID 22007769.
- ^ Heading C (February 2001). "Siramesine H Lundbeck". Current Opinion in Investigational Drugs. 2 (2): 266–70. PMID 11816842.
- ^ Skuza G, Rogoz Z (June 2006). "The synergistic effect of selective sigma receptor agonists and uncompetitive NMDA receptor antagonists in the forced swim test in rats" (PDF). Journal of Physiology and Pharmacology. 57 (2): 217–29. PMID 16845227.
- ^ Nuwayhid SJ, Werling LL (March 2006). "Sigma2 (sigma2) receptors as a target for cocaine action in the rat striatum". European Journal of Pharmacology. 535 (1–3): 98–103. doi:10.1016/j.ejphar.2005.12.077. PMID 16480713.
- ^ Ostenfeld MS, Fehrenbacher N, Høyer-Hansen M, Thomsen C, Farkas T, Jäättelä M (October 2005). "Effective tumor cell death by sigma-2 receptor ligand siramesine involves lysosomal leakage and oxidative stress". Cancer Research. 65 (19): 8975–83. doi:10.1158/0008-5472.CAN-05-0269. PMID 16204071.
- ^ Groth-Pedersen L, Ostenfeld MS, Høyer-Hansen M, Nylandsted J, Jäättelä M (March 2007). "Vincristine induces dramatic lysosomal changes and sensitizes cancer cells to lysosome-destabilizing siramesine". Cancer Research. 67 (5): 2217–25. doi:10.1158/0008-5472.CAN-06-3520. PMID 17332352.
External links
- Siramesine at the U.S. National Library of Medicine Medical Subject Headings (MeSH)