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Ro5-4864

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Chemical compound Pharmaceutical compound
Ro5-4864
Legal status
Legal status
Identifiers
IUPAC name
  • 7-Chloro-5-(4-chlorophenyl)-1-methyl-3H-1,4-benzodiazepin-2-one
CAS Number
PubChem CID
ChemSpider
UNII
CompTox Dashboard (EPA)
ECHA InfoCard100.162.290 Edit this at Wikidata
Chemical and physical data
FormulaC16H12Cl2N2O
Molar mass319.19 g·mol
3D model (JSmol)
SMILES
  • Clc3ccc(cc3)C(=NCC1=O)c2cc(Cl)ccc2N1C
InChI
  • InChI=1S/C16H12Cl2N2O/c1-20-14-7-6-12(18)8-13(14)16(19-9-15(20)21)10-2-4-11(17)5-3-10/h2-8H,9H2,1H3
  • Key:PUMYFTJOWAJIKF-UHFFFAOYSA-N
  (what is this?)  (verify)

Ro5-4864 (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, instead being sedative yet also convulsant and anxiogenic in effects. Ro5-4864 was found to be a potent ligand for the "peripheral benzodiazepine receptor", 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. In vitro studies and rodent models also suggest the possibility of analgesic, antidepressant, cardioprotective, and anti-cancer effects.

See also

References

  1. US 3136815, Reeder E, Sternbach LH, "Amino substituted benzophenone oximes and derivatives thereof", issued 9 June 1964, assigned to F Hoffmann La Roche AG 
  2. 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.
  3. Patel J, Marangos PJ (May 1982). "Differential effects of GABA on peripheral and central type benzodiazepine binding sites in brain". Neuroscience Letters. 30 (2): 157–160. doi:10.1016/0304-3940(82)90289-0. PMID 6287365. S2CID 19728357.
  4. 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: 139–151. PMID 6670623.
  5. File SE, Lister RG (January 1983). "The anxiogenic action of Ro 5-4864 is reversed by phenytoin". Neuroscience Letters. 35 (1): 93–96. doi:10.1016/0304-3940(83)90532-3. PMID 6682534. S2CID 11977458.
  6. 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. S2CID 28892522.
  7. 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.
  8. Marangos PJ, Patel J, Boulenger JP, Clark-Rosenberg R (July 1982). "Characterization of peripheral-type benzodiazepine binding sites in brain using Ro 5-4864". Molecular Pharmacology. 22 (1): 26–32. PMID 6289073.
  9. 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.
  10. 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.
  11. 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.
  12. Mills C, Makwana M, Wallace A, Benn S, Schmidt H, Tegeder I, et al. (February 2008). "Ro5-4864 promotes neonatal motor neuron survival and nerve regeneration in adult rats". The European Journal of Neuroscience. 27 (4): 937–946. doi:10.1111/j.1460-9568.2008.06065.x. PMID 18333964. S2CID 40302403.
  13. 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): 201–208. doi:10.1016/j.expneurol.2008.08.008. PMID 18789929. S2CID 2252586.
  14. 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.
  15. DalBó S, Nardi GM, Ferrara P, Ribeiro-do-Valle RM, Farges RC (April 2004). "Antinociceptive effects of peripheral benzodiazepine receptors". Pharmacology. 70 (4): 188–194. doi:10.1159/000075547. PMID 15001819. S2CID 1116731.
  16. 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.
  17. 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.
  18. 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.
  19. 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.
  20. 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.
  21. 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.
Benzodiazepines
1,4-Benzodiazepines
1,5-Benzodiazepines
2,3-Benzodiazepines*
Triazolobenzodiazepines
Imidazobenzodiazepines
Oxazolobenzodiazepines
Thienodiazepines
Thienotriazolodiazepines
Thienobenzodiazepines*
Pyridodiazepines
Pyridotriazolodiazepines
Pyrazolodiazepines
Pyrrolodiazepines
Tetrahydroisoquinobenzodiazepines
Pyrrolobenzodiazepines*
Benzodiazepine prodrugs
* atypical activity profile (not GABAA receptor ligands)
Translocator protein modulators
Agonists
Antagonists
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