Rimcazole Explained

Rimcazole is an antagonist^[1] of the sigma receptor^[2] as well as a dopamine reuptake inhibitor.^[3] Sigma receptors are thought to be involved in the drug psychosis that can be induced by some drugs such as phencyclidine and cocaine, and rimcazole was originally researched as a potential antipsychotic with a different mechanism of action to traditional antipsychotic drugs. Trials proved inconclusive and rimcazole was not pursued for this application, but other sigma antagonists continue to be researched for a variety of potential applications.^[4] Rimcazole has been shown to reduce the effects of cocaine,^[5] and analogues of rimcazole have been shown to be highly effective at blocking the convulsions caused by cocaine overdose in animal models.^[6]

Notes and References

1. Gilmore DL, Liu Y, Matsumoto RR . Review of the pharmacological and clinical profile of rimcazole . CNS Drug Reviews . 10 . 1 . 1–22 . 2004 . 14978511 . 6741722 . 10.1111/j.1527-3458.2004.tb00001.x .
2. Eaton MJ, Lookingland KJ, Moore KE . The sigma ligand rimcazole activates noradrenergic neurons projecting to the paraventricular nucleus and increases corticosterone secretion in rats . Brain Research . 733 . 2 . 162–166 . September 1996 . 8891298 . 10.1016/0006-8993(96)00290-9 . 42885767 .
3. Husbands SM, Izenwasser S, Loeloff RJ, Katz JL, Bowen WD, Vilner BJ, Newman AH . Isothiocyanate derivatives of 9-[3-(cis-3,5-dimethyl-1-piperazinyl)propyl]carbazole (rimcazole): irreversible ligands for the dopamine transporter . Journal of Medicinal Chemistry . 40 . 26 . 4340–4346 . December 1997 . 9435903 . 10.1021/jm9705519 .
4. Volz HP, Stoll KD . Clinical trials with sigma ligands . Pharmacopsychiatry . 37 . Suppl 3. S214–S220 . November 2004 . 15547788 . 10.1055/s-2004-832680 . 260238757 .
5. Katz JL, Libby TA, Kopajtic T, Husbands SM, Newman AH . Behavioral effects of rimcazole analogues alone and in combination with cocaine . European Journal of Pharmacology . 468 . 2 . 109–119 . May 2003 . 12742518 . 10.1016/s0014-2999(03)01638-8 .
6. Matsumoto RR, Hewett KL, Pouw B, Bowen WD, Husbands SM, Cao JJ, Newman AH . Rimcazole analogs attenuate the convulsive effects of cocaine: correlation with binding to sigma receptors rather than dopamine transporters . Neuropharmacology . 41 . 7 . 878–886 . December 2001 . 11684152 . 10.1016/s0028-3908(01)00116-2 . 44328858 .