Ro5-4864
Ro5-4864
Chemical compound
Ro5-4864[1] (4'-chlorodiazepam) is a drug which is a benzodiazepine derivative of diazepam.[2] However unlike most benzodiazepine derivatives, Ro5-4864 lacks affinity for GABAA receptors and lacks typical benzodiazepine effects,[3] instead being sedative yet also convulsant and anxiogenic in effects.[4][5][6][7] Ro5-4864 was found to be a potent ligand for the "peripheral benzodiazepine receptor",[8] later renamed to mitochondrial translocator protein 18kDa (TSPO). Despite its convulsant effects, at lower doses Ro5-4864 has proved to be neuroprotective and has become widely used for research into the role of the TSPO protein in neurotoxicity.[9][10][11][12][13][14] In vitro studies and rodent models also suggest the possibility of analgesic,[15] antidepressant,[16] cardioprotective,[17] and anti-cancer effects.[18][19][20][21][non-primary source needed]
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ECHA InfoCard | 100.162.290 |
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Formula | C16H12Cl2N2O |
Molar mass | 319.19 g·mol−1 |
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- Diclazepam (2'-chlorodiazepam)
- PK-11195
- US 3136815, Reeder E, Sternbach LH, "Amino substituted benzophenone oximes and derivatives thereof", issued 9 June 1964, assigned to F Hoffmann La Roche AG
- Manchester KR, Maskell PD, Waters L (March 2018). "Experimental versus theoretical log D7.4 , pKa and plasma protein binding values for benzodiazepines appearing as new psychoactive substances". Drug Testing and Analysis. 10 (8): 1258–1269. doi:10.1002/dta.2387. PMID 29582576. S2CID 31098917.
- Pellow S, File SE (July 1984). "Behavioural actions of Ro 5-4864: a peripheral-type benzodiazepine?". Life Sciences. 35 (3): 229–240. doi:10.1016/0024-3205(84)90106-1. PMID 6087055.
- Veiga S, Azcoitia I, Garcia-Segura LM (April 2005). "Ro5-4864, a peripheral benzodiazepine receptor ligand, reduces reactive gliosis and protects hippocampal hilar neurons from kainic acid excitotoxicity". Journal of Neuroscience Research. 80 (1): 129–137. doi:10.1002/jnr.20430. hdl:10261/72513. PMID 15696538. S2CID 23955844.
- Leonelli E, Yague JG, Ballabio M, Azcoitia I, Magnaghi V, Schumacher M, et al. (November 2005). "Ro5-4864, a synthetic ligand of peripheral benzodiazepine receptor, reduces aging-associated myelin degeneration in the sciatic nerve of male rats". Mechanisms of Ageing and Development. 126 (11): 1159–1163. doi:10.1016/j.mad.2005.06.001. hdl:10261/72157. PMID 16045970. S2CID 45797879.
- Azarashvili T, Grachev D, Krestinina O, Evtodienko Y, Yurkov I, Papadopoulos V, Reiser G (July 2007). "The peripheral-type benzodiazepine receptor is involved in control of Ca2+-induced permeability transition pore opening in rat brain mitochondria". Cell Calcium. 42 (1): 27–39. doi:10.1016/j.ceca.2006.11.004. PMID 17174393.
- Giatti S, Pesaresi M, Cavaletti G, Bianchi R, Carozzi V, Lombardi R, et al. (December 2009). "Neuroprotective effects of a ligand of translocator protein-18 kDa (Ro5-4864) in experimental diabetic neuropathy". Neuroscience. 164 (2): 520–529. doi:10.1016/j.neuroscience.2009.08.005. hdl:10261/72515. PMID 19665520. S2CID 11551493.
- Gavioli EC, Duarte FS, Bressan E, Ferrara P, Farges RC, De Lima TC (June 2003). "Antidepressant-like effect of Ro5-4864, a peripheral-type benzodiazepine receptor ligand, in forced swimming test". European Journal of Pharmacology. 471 (1): 21–26. doi:10.1016/S0014-2999(03)01789-8. PMID 12809948.
- Solhjoo S, O'Rourke B (January 2015). "Mitochondrial instability during regional ischemia-reperfusion underlies arrhythmias in monolayers of cardiomyocytes". Journal of Molecular and Cellular Cardiology. 78: 90–99. doi:10.1016/j.yjmcc.2014.09.024. PMC 4268014. PMID 25268650.
- Obame FN, Zini R, Souktani R, Berdeaux A, Morin D (October 2007). "Peripheral benzodiazepine receptor-induced myocardial protection is mediated by inhibition of mitochondrial membrane permeabilization". The Journal of Pharmacology and Experimental Therapeutics. 323 (1): 336–345. doi:10.1124/jpet.107.124255. PMID 17640950. S2CID 12215031.
- Veenman L, Papadopoulos V, Gavish M (2007). "Channel-like functions of the 18-kDa translocator protein (TSPO): regulation of apoptosis and steroidogenesis as part of the host-defense response". Current Pharmaceutical Design. 13 (23): 2385–2405. doi:10.2174/138161207781368710. PMID 17692008.
- Papadopoulos V, Lecanu L (September 2009). "Translocator protein (18 kDa) TSPO: an emerging therapeutic target in neurotrauma". Experimental Neurology. 219 (1): 53–57. doi:10.1016/j.expneurol.2009.04.016. PMC 2728790. PMID 19409385.
- Xiao J, Liang D, Zhang H, Liu Y, Li F, Chen YH (April 2010). "4'-Chlorodiazepam, a translocator protein (18 kDa) antagonist, improves cardiac functional recovery during postischemia reperfusion in rats". Experimental Biology and Medicine. 235 (4): 478–486. doi:10.1258/ebm.2009.009291. PMID 20407080. S2CID 6403616.