Siramesine

Siramesine

Clinical data
ATC code	none
Identifiers
IUPAC name 1'-{4-[1-(4-fluorophenyl)-1H-indol-3-yl]butyl}-3H-spiro[2-benzofuran-1,4'-piperidine]
CAS Number	147817-50-3
PubChem (CID)	9829526
ChemSpider	8005261
UNII	3IX8CWR24V
Chemical and physical data
Formula	C30H31FN2O
Molar mass	454.59 g/mol
3D model (Jmol)	Interactive image
SMILES C1CN(CCC12C3=CC=CC=C3CO2)CCCCC4=CN(C5=CC=CC=C54)C6=CC=C(C=C6)F
InChI 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 Key:XWAONOGAGZNUSF-UHFFFAOYSA-N
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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

1. Soby KK, Mikkelsen JD, Meier E, Thomsen C. Lu 28-179 labels a sigma(2)-site in rat and human brain. Neuropharmacology. 2002 Jul;43(1):95-100.
2. Sanchez C, Arnt J, Costall B, Kelly ME, Meier E, Naylor RJ, Perregaard J. The selective sigma2-ligand Lu 28-179 has potent anxiolytic-like effects in rodents. Journal of Pharmacology and Experimental Therapeutics. 1997 Dec;283(3):1323-32.
3. Sanchez C, Papp M. The selective sigma2 ligand Lu 28-179 has an antidepressant-like profile in the rat chronic mild stress model of depression. Behavioural Pharmacology. 2000 Apr;11(2):117-24.
4. Heading C. Siramesine H Lundbeck. Current Opinion in Investigational Drugs. 2001 Feb;2(2):266-70.
5. Skuza G, Rogoz Z. The synergistic effect of selective sigma receptor agonists and uncompetitive NMDA receptor antagonists in the forced swim test in rats. Journal of Physiology and Pharmacology. 2006 Jun;57(2):217-29.
6. Nuwayhid SJ, Werling LL. Sigma2 (σ2) receptors as a target for cocaine action in the rat striatum. European Journal of Pharmacology. 2006 Mar 27;535(1-3):98-103.
7. Ostenfeld MS, Fehrenbacher N, Hoyer-Hansen M, Thomsen C, Farkas T, Jaattela M. Effective tumor cell death by sigma-2 receptor ligand siramesine involves lysosomal leakage and oxidative stress. Cancer Research. 2005 Oct 1;65(19):8975-83.
8. Groth-Pedersen L, Ostenfeld MS, Hoyer-Hansen M, Nylandsted J, Jaattela M. Vincristine induces dramatic lysosomal changes and sensitizes cancer cells to lysosome-destabilizing siramesine. Cancer Research. 2007 Mar 1;67(5):2217-25.

External links

• Siramesine at the US National Library of Medicine Medical Subject Headings (MeSH)