Ro5-4864

Ro5-4864
Systematic (IUPAC) name
7-Chloro-5-(4-chlorophenyl)-1-methyl-3H-1,4-benzodiazepin-2-one
Clinical data
Legal status
  • Not FDA approved
Identifiers
CAS Number 14439-61-3 YesY
PubChem CID 1688
ChemSpider 1625
Chemical data
Formula C16H12Cl2N2O
Molar mass 319.185
  (verify)

Ro5-4864[1] (4'-chlorodiazepam) is a drug which is a benzodiazepine derivative of diazepam. However unlike most benzodiazepine derivatives, Ro5-4864 lacks affinity for GABAA receptors and lacks typical benzodiazepine effects,[2] instead being sedative yet also convulsant and anxiogenic in effects.[3][4][5][6] Ro5-4864 was found to be a potent ligand for the "peripheral benzodiazepine receptor",[7] 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.[8][9][10][11][12][13] In vitro studies and rodent models also suggest the possibility of analgesic,[14] antidepressant,[15] cardioprotective,[16] and anti-cancer effects.[17][18][19][20]

See also

References

  1. US 3136815
  2. Patel J, Marangos PJ (May 1982). "Differential effects of GABA on peripheral and central type benzodiazepine binding sites in brain". Neuroscience Letters 30 (2): 157–60. doi:10.1016/0304-3940(82)90289-0. PMID 6287365.
  3. Weissman BA, Cott J, Hommer D, Quirion R, Paul S, Skolnick P (1983). "Pharmacological, electrophysiological, and neurochemical actions of the convulsant benzodiazepine Ro 5-4864 (4'-chlordiazepam)". Advances in Biochemical Psychopharmacology 38: 139–51. PMID 6670623.
  4. File SE, Lister RG (January 1983). "The anxiogenic action of Ro 5-4864 is reversed by phenytoin". Neuroscience Letters 35 (1): 93–6. doi:10.1016/0304-3940(83)90532-3. PMID 6682534.
  5. File SE, Green AR, Nutt DJ, Vincent ND (1984). "On the convulsant action of Ro 5-4864 and the existence of a micromolar benzodiazepine binding site in rat brain". Psychopharmacology 82 (3): 199–202. doi:10.1007/BF00427773. PMID 6326177.
  6. Pellow S, File SE (July 1984). "Behavioural actions of Ro 5-4864: a peripheral-type benzodiazepine?". Life Sciences 35 (3): 229–40. doi:10.1016/0024-3205(84)90106-1. PMID 6087055.
  7. Marangos PJ, Patel J, Boulenger JP, Clark-Rosenberg R (July 1982). "Characterization of peripheral-type benzodiazepine binding sites in brain using [3H]Ro 5-4864". Molecular Pharmacology 22 (1): 26–32. PMID 6289073.
  8. 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): 129–37. doi:10.1002/jnr.20430. PMID 15696538.
  9. Leonelli E, Yague JG, Ballabio M, Azcoitia I, Magnaghi V, Schumacher M, Garcia-Segura LM, Melcangi RC (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): 1159–63. doi:10.1016/j.mad.2005.06.001. PMID 16045970.
  10. 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.
  11. Mills C, Makwana M, Wallace A, Benn S, Schmidt H, Tegeder I, Costigan M, Brown RH, Raivich G, Woolf CJ (February 2008). "Ro5-4864 promotes neonatal motor neuron survival and nerve regeneration in adult rats". The European Journal of Neuroscience 27 (4): 937–46. doi:10.1111/j.1460-9568.2008.06065.x. PMID 18333964.
  12. Soustiel JF, Zaaroor M, Vlodavsky E, Veenman L, Weizman A, Gavish M (December 2008). "Neuroprotective effect of Ro5-4864 following brain injury". Experimental Neurology 214 (2): 201–8. doi:10.1016/j.expneurol.2008.08.008. PMID 18789929.
  13. Giatti S, Pesaresi M, Cavaletti G, Bianchi R, Carozzi V, Lombardi R, Maschi O, Lauria G, Garcia-Segura LM, Caruso D, Melcangi RC (December 2009). "Neuroprotective effects of a ligand of translocator protein-18 kDa (Ro5-4864) in experimental diabetic neuropathy". Neuroscience 164 (2): 520–9. doi:10.1016/j.neuroscience.2009.08.005. PMID 19665520.
  14. DalBó S, Nardi GM, Ferrara P, Ribeiro-do-Valle RM, Farges RC (April 2004). "Antinociceptive effects of peripheral benzodiazepine receptors". Pharmacology 70 (4): 188–94. doi:10.1159/000075547. PMID 15001819.
  15. 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): 21–6. doi:10.1016/S0014-2999(03)01789-8. PMID 12809948.
  16. 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: 90–9. doi:10.1016/j.yjmcc.2014.09.024. PMID 25268650.
  17. 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): 336–45. doi:10.1124/jpet.107.124255. PMID 17640950.
  18. 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): 2385–405. doi:10.2174/138161207781368710. PMID 17692008.
  19. Papadopoulos V, Lecanu L (September 2009). "Translocator protein (18 kDa) TSPO: an emerging therapeutic target in neurotrauma". Experimental Neurology 219 (1): 53–7. doi:10.1016/j.expneurol.2009.04.016. PMC 2728790. PMID 19409385.
  20. 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 (Maywood, N.J.) 235 (4): 478–86. doi:10.1258/ebm.2009.009291. PMID 20407080.
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