Siramesine Explained

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]

Notes and References

1. Søby KK, Mikkelsen JD, Meier E, Thomsen C . Lu 28-179 labels a sigma(2)-site in rat and human brain . Neuropharmacology . 43 . 1 . 95–100 . July 2002 . 12213263 . 10.1016/s0028-3908(02)00071-0 . 140206932 .
2. Sánchez 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 . The Journal of Pharmacology and Experimental Therapeutics . 283 . 3 . 1323–32 . December 1997 . 9400007 .
3. Sánchez 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 . 11 . 2 . 117–24 . April 2000 . 10877116 . 10.1097/00008877-200004000-00003 . 22007769 .
4. Heading C . Siramesine H Lundbeck . Current Opinion in Investigational Drugs . 2 . 2 . 266–70 . February 2001 . 11816842 .
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 . June 2006 . 57 . 2 . 217–29 . 16845227 .
6. Nuwayhid SJ, Werling LL . Sigma2 (sigma2) receptors as a target for cocaine action in the rat striatum . European Journal of Pharmacology . 535 . 1–3 . 98–103 . March 2006 . 16480713 . 10.1016/j.ejphar.2005.12.077 .
7. Ostenfeld MS, Fehrenbacher N, Høyer-Hansen M, Thomsen C, Farkas T, Jäättelä M . Effective tumor cell death by sigma-2 receptor ligand siramesine involves lysosomal leakage and oxidative stress . Cancer Research . 65 . 19 . 8975–83 . October 2005 . 16204071 . 10.1158/0008-5472.CAN-05-0269 .
8. Groth-Pedersen L, Ostenfeld MS, Høyer-Hansen M, Nylandsted J, Jäättelä M . Vincristine induces dramatic lysosomal changes and sensitizes cancer cells to lysosome-destabilizing siramesine . Cancer Research . 67 . 5 . 2217–25 . March 2007 . 17332352 . 10.1158/0008-5472.CAN-06-3520 .