Siramesine

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]

Siramesine
Clinical data
ATC code
  • none
Identifiers
  • 1'-{4-[1-(4-Fluorophenyl)-1H-indol-3-yl]butyl}-3H-spiro[2-benzofuran-1,4'-piperidine]
CAS Number
PubChem CID
ChemSpider
UNII
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC30H31FN2O
Molar mass454.589 g·mol−1
3D model (JSmol)
  • C1CN(CCC12C3=CC=CC=C3CO2)CCCCC4=CN(C5=CC=CC=C54)C6=CC=C(C=C6)F
  • InChI=1S/C30H31FN2O/c31-25-12-14-26(15-13-25)33-21-23(27-9-2-4-11-29(27)33)7-5-6-18-32-19-16-30(17-20-32)28-10-3-1-8-24(28)22-34-30/h1-4,8-15,21H,5-7,16-20,22H2 ☒N
  • Key:XWAONOGAGZNUSF-UHFFFAOYSA-N ☒N
 ☒NcheckY (what is this?)  (verify)

References
  1. 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.
  2. 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.
  3. 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.
  4. Heading C (February 2001). "Siramesine H Lundbeck". Current Opinion in Investigational Drugs. 2 (2): 266–70. PMID 11816842.
  5. 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.
  6. 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.
  7. 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.
  8. 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.


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