siramesine

{{Short description|Chemical compound}}

{{Drugbox

| Verifiedfields = changed

| verifiedrevid = 447773166

| IUPAC_name = 1'-{4-[1-(4-Fluorophenyl)-1H-indol-3-yl]butyl}-3H-spiro[2-benzofuran-1,4'-piperidine]

| image = Siramesine1.svg

| width = 220

| image2 = Siramesine-3D.png

| width2 = 220

| tradename =

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| CAS_number_Ref = {{cascite|correct|??}}

| CAS_number = 147817-50-3

| ATC_prefix = none

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| PubChem = 9829526

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = 3IX8CWR24V

| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}

| ChemSpiderID = 8005261

| C=30 | H=31 | F=1 | N=2 | O=1

| smiles = C1CN(CCC12C3=CC=CC=C3CO2)CCCCC4=CN(C5=CC=CC=C54)C6=CC=C(C=C6)F

| StdInChI_Ref = {{stdinchicite|changed|chemspider}}

| StdInChI = 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

| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}

| StdInChIKey = XWAONOGAGZNUSF-UHFFFAOYSA-N

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Siramesine (or Lu 28-179) is a sigma receptor agonist, selective for the σ2 subtype.{{cite journal | vauthors = Søby KK, Mikkelsen JD, Meier E, Thomsen C | title = Lu 28-179 labels a sigma(2)-site in rat and human brain | journal = Neuropharmacology | volume = 43 | issue = 1 | pages = 95–100 | date = July 2002 | pmid = 12213263 | doi = 10.1016/s0028-3908(02)00071-0 | s2cid = 140206932 }} In animal studies, siramesine has been shown to produce anxiolytic{{cite journal | vauthors = Sánchez C, Arnt J, Costall B, Kelly ME, Meier E, Naylor RJ, Perregaard J | title = The selective sigma2-ligand Lu 28-179 has potent anxiolytic-like effects in rodents | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 283 | issue = 3 | pages = 1323–32 | date = December 1997 | doi = 10.1016/S0022-3565(24)37124-1 | pmid = 9400007 }} and antidepressant{{cite journal | vauthors = Sánchez C, Papp M | title = The selective sigma2 ligand Lu 28-179 has an antidepressant-like profile in the rat chronic mild stress model of depression | journal = Behavioural Pharmacology | volume = 11 | issue = 2 | pages = 117–24 | date = April 2000 | pmid = 10877116 | doi = 10.1097/00008877-200004000-00003 | s2cid = 22007769 }} effects. It was developed by the pharmaceutical company H Lundbeck for the treatment of anxiety,{{cite journal | vauthors = Heading C | title = Siramesine H Lundbeck | journal = Current Opinion in Investigational Drugs | volume = 2 | issue = 2 | pages = 266–70 | date = February 2001 | pmid = 11816842 }} 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.{{cite journal | vauthors = Skuza G, Rogoz Z | title = The synergistic effect of selective sigma receptor agonists and uncompetitive NMDA receptor antagonists in the forced swim test in rats. | journal = Journal of Physiology and Pharmacology | date = June 2006 | volume = 57 | issue = 2 | pages = 217–29 | pmid = 16845227 | url = http://jpp.krakow.pl/journal/archive/06_06/pdf/217_06_06_article.pdf }} It has also been used to study the σ2 activity of cocaine,{{cite journal | vauthors = Nuwayhid SJ, Werling LL | title = Sigma2 (sigma2) receptors as a target for cocaine action in the rat striatum | journal = European Journal of Pharmacology | volume = 535 | issue = 1–3 | pages = 98–103 | date = March 2006 | pmid = 16480713 | doi = 10.1016/j.ejphar.2005.12.077 }} and has been shown to produce anticancer properties both in vitro{{cite journal | vauthors = Ostenfeld MS, Fehrenbacher N, Høyer-Hansen M, Thomsen C, Farkas T, Jäättelä M | title = Effective tumor cell death by sigma-2 receptor ligand siramesine involves lysosomal leakage and oxidative stress | journal = Cancer Research | volume = 65 | issue = 19 | pages = 8975–83 | date = October 2005 | pmid = 16204071 | doi = 10.1158/0008-5472.CAN-05-0269 | doi-access = }} and in vivo.{{cite journal | vauthors = Groth-Pedersen L, Ostenfeld MS, Høyer-Hansen M, Nylandsted J, Jäättelä M | title = Vincristine induces dramatic lysosomal changes and sensitizes cancer cells to lysosome-destabilizing siramesine | journal = Cancer Research | volume = 67 | issue = 5 | pages = 2217–25 | date = March 2007 | pmid = 17332352 | doi = 10.1158/0008-5472.CAN-06-3520 | doi-access = }}