View source for Ro5-4864

{{Short description|Chemical compound}}
{{Drugbox
| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 451564612
| IUPAC_name = 7-Chloro-5-(4-chlorophenyl)-1-methyl-3''H''-1,4-benzodiazepin-2-one
| image = Ro5-4864.svg
| width = 177
<!--Clinical data-->
| tradename =
| legal_CA = Schedule IV
| legal_DE = NpSG
| legal_UK = PSA
| legal_US = Not FDA approved
<!--Pharmacokinetic data-->
| bioavailability =
| metabolism =
| elimination_half-life =
| excretion =
<!--Identifiers-->
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 14439-61-3
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 2QW0IK1742
| ATC_prefix =
| PubChem = 1688
| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}
| ChemSpiderID = 1625
<!--Chemical data-->
| C=16 | H=12 | Cl=2 | N=2 | O=1
| smiles = Clc3ccc(cc3)C(=NCC1=O)c2cc(Cl)ccc2N1C
| StdInChI_Ref = {{stdinchicite|changed|chemspider}}
| StdInChI = 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
| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}
| StdInChIKey = PUMYFTJOWAJIKF-UHFFFAOYSA-N
}}
'''Ro5-4864'''<ref>{{cite patent | country = US | number = 3136815 | title = Amino substituted benzophenone oximes and derivatives thereof  | inventor = Reeder E, Sternbach LH | assign1 = F Hoffmann La Roche AG | gdate = 9 June 1964 }}</ref> ('''4'-chlorodiazepam''') is a drug which is a [[benzodiazepine]] derivative of [[diazepam]].<ref>{{cite journal | vauthors = Manchester KR, Maskell PD, Waters L | title = Experimental versus theoretical log D<sub>7.4</sub> , pK<sub>a</sub> and plasma protein binding values for benzodiazepines appearing as new psychoactive substances | journal = Drug Testing and Analysis | volume = 10 | issue = 8 | pages = 1258–1269 | date = March 2018 | pmid = 29582576 | doi = 10.1002/dta.2387 | s2cid = 31098917 | url = https://rke.abertay.ac.uk/en/publications/527a634d-decc-4d3a-bdca-08659bb13ed6 }}</ref> However unlike most benzodiazepine derivatives, Ro5-4864 lacks affinity for [[GABAA receptor|GABA<sub>A</sub>]] [[Receptor (biochemistry)|receptors]] and lacks typical benzodiazepine effects,<ref name="pmid6287365">{{cite journal | vauthors = Patel J, Marangos PJ | title = Differential effects of GABA on peripheral and central type benzodiazepine binding sites in brain | journal = Neuroscience Letters | volume = 30 | issue = 2 | pages = 157–160 | date = May 1982 | pmid = 6287365 | doi = 10.1016/0304-3940(82)90289-0 | s2cid = 19728357 }}</ref> instead being [[sedative]] yet also [[convulsant]] and [[anxiogenic]] in effects.<ref name="pmid6670623">{{cite journal | vauthors = Weissman BA, Cott J, Hommer D, Quirion R, Paul S, Skolnick P | title = Pharmacological, electrophysiological, and neurochemical actions of the convulsant benzodiazepine Ro 5-4864 (4'-chlordiazepam) | journal = Advances in Biochemical Psychopharmacology | volume = 38 | pages = 139–151 | year = 1983 | pmid = 6670623 }}</ref><ref name="pmid6682534">{{cite journal | vauthors = File SE, Lister RG | title = The anxiogenic action of Ro 5-4864 is reversed by phenytoin | journal = Neuroscience Letters | volume = 35 | issue = 1 | pages = 93–96 | date = January 1983 | pmid = 6682534 | doi = 10.1016/0304-3940(83)90532-3 | s2cid = 11977458 }}</ref><ref name="pmid6326177">{{cite journal | vauthors = File SE, Green AR, Nutt DJ, Vincent ND | title = On the convulsant action of Ro 5-4864 and the existence of a micromolar benzodiazepine binding site in rat brain | journal = Psychopharmacology | volume = 82 | issue = 3 | pages = 199–202 | year = 1984 | pmid = 6326177 | doi = 10.1007/BF00427773 | s2cid = 28892522 }}</ref><ref name="pmid6087055">{{cite journal | vauthors = Pellow S, File SE | title = Behavioural actions of Ro 5-4864: a peripheral-type benzodiazepine? | journal = Life Sciences | volume = 35 | issue = 3 | pages = 229–240 | date = July 1984 | pmid = 6087055 | doi = 10.1016/0024-3205(84)90106-1 }}</ref> Ro5-4864 was found to be a potent ligand for the "peripheral benzodiazepine receptor",<ref name="pmid6289073">{{cite journal | vauthors = Marangos PJ, Patel J, Boulenger JP, Clark-Rosenberg R | title = Characterization of peripheral-type benzodiazepine binding sites in brain using [3H]Ro 5-4864 | journal = Molecular Pharmacology | volume = 22 | issue = 1 | pages = 26–32 | date = July 1982 | pmid = 6289073 }}</ref> later renamed to [[TSPO (protein)|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]].<ref name="pmid15696538">{{cite journal | vauthors = Veiga S, Azcoitia I, Garcia-Segura LM | title = Ro5-4864, a peripheral benzodiazepine receptor ligand, reduces reactive gliosis and protects hippocampal hilar neurons from kainic acid excitotoxicity | journal = Journal of Neuroscience Research | volume = 80 | issue = 1 | pages = 129–137 | date = April 2005 | pmid = 15696538 | doi = 10.1002/jnr.20430 | hdl-access = free | s2cid = 23955844 | hdl = 10261/72513 }}</ref><ref name="pmid16045970">{{cite journal | vauthors = Leonelli E, Yague JG, Ballabio M, Azcoitia I, Magnaghi V, Schumacher M, Garcia-Segura LM, Melcangi RC | display-authors = 6 | title = Ro5-4864, a synthetic ligand of peripheral benzodiazepine receptor, reduces aging-associated myelin degeneration in the sciatic nerve of male rats | journal = Mechanisms of Ageing and Development | volume = 126 | issue = 11 | pages = 1159–1163 | date = November 2005 | pmid = 16045970 | doi = 10.1016/j.mad.2005.06.001 | s2cid = 45797879 | hdl = 10261/72157 }}</ref><ref name="pmid17174393">{{cite journal | vauthors = Azarashvili T, Grachev D, Krestinina O, Evtodienko Y, Yurkov I, Papadopoulos V, Reiser G | title = The peripheral-type benzodiazepine receptor is involved in control of Ca2+-induced permeability transition pore opening in rat brain mitochondria | journal = Cell Calcium | volume = 42 | issue = 1 | pages = 27–39 | date = July 2007 | pmid = 17174393 | doi = 10.1016/j.ceca.2006.11.004 }}</ref><ref name="pmid18333964">{{cite journal | vauthors = Mills C, Makwana M, Wallace A, Benn S, Schmidt H, Tegeder I, Costigan M, Brown RH, Raivich G, Woolf CJ | display-authors = 6 | title = Ro5-4864 promotes neonatal motor neuron survival and nerve regeneration in adult rats | journal = The European Journal of Neuroscience | volume = 27 | issue = 4 | pages = 937–946 | date = February 2008 | pmid = 18333964 | doi = 10.1111/j.1460-9568.2008.06065.x | s2cid = 40302403 }}</ref><ref name="pmid18789929">{{cite journal | vauthors = Soustiel JF, Zaaroor M, Vlodavsky E, Veenman L, Weizman A, Gavish M | title = Neuroprotective effect of Ro5-4864 following brain injury | journal = Experimental Neurology | volume = 214 | issue = 2 | pages = 201–208 | date = December 2008 | pmid = 18789929 | doi = 10.1016/j.expneurol.2008.08.008 | s2cid = 2252586 }}</ref><ref name="pmid19665520">{{cite journal | vauthors = Giatti S, Pesaresi M, Cavaletti G, Bianchi R, Carozzi V, Lombardi R, Maschi O, Lauria G, Garcia-Segura LM, Caruso D, Melcangi RC | display-authors = 6 | title = Neuroprotective effects of a ligand of translocator protein-18 kDa (Ro5-4864) in experimental diabetic neuropathy | journal = Neuroscience | volume = 164 | issue = 2 | pages = 520–529 | date = December 2009 | pmid = 19665520 | doi = 10.1016/j.neuroscience.2009.08.005 | hdl-access = free | s2cid = 11551493 | hdl = 10261/72515 }}</ref> ''[[In vitro]]'' studies and [[rodent model]]s also suggest the possibility of [[analgesic]],<ref name="pmid15001819">{{cite journal | vauthors = DalBó S, Nardi GM, Ferrara P, Ribeiro-do-Valle RM, Farges RC | title = Antinociceptive effects of peripheral benzodiazepine receptors | journal = Pharmacology | volume = 70 | issue = 4 | pages = 188–194 | date = April 2004 | pmid = 15001819 | doi = 10.1159/000075547 | s2cid = 1116731 }}</ref> [[antidepressant]],<ref name="pmid12809948">{{cite journal | vauthors = Gavioli EC, Duarte FS, Bressan E, Ferrara P, Farges RC, De Lima TC | title = Antidepressant-like effect of Ro5-4864, a peripheral-type benzodiazepine receptor ligand, in forced swimming test | journal = European Journal of Pharmacology | volume = 471 | issue = 1 | pages = 21–26 | date = June 2003 | pmid = 12809948 | doi = 10.1016/S0014-2999(03)01789-8 }}</ref> cardioprotective,<ref name="pmid25268650">{{cite journal | vauthors = Solhjoo S, O'Rourke B | title = Mitochondrial instability during regional ischemia-reperfusion underlies arrhythmias in monolayers of cardiomyocytes | journal = Journal of Molecular and Cellular Cardiology | volume = 78 | pages = 90–99 | date = January 2015 | pmid = 25268650 | pmc = 4268014 | doi = 10.1016/j.yjmcc.2014.09.024 }}</ref> and anti-cancer effects.<ref name="pmid17640950">{{cite journal | vauthors = Obame FN, Zini R, Souktani R, Berdeaux A, Morin D | title = Peripheral benzodiazepine receptor-induced myocardial protection is mediated by inhibition of mitochondrial membrane permeabilization | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 323 | issue = 1 | pages = 336–345 | date = October 2007 | pmid = 17640950 | doi = 10.1124/jpet.107.124255 | s2cid = 12215031 }}</ref><ref name="pmid17692008">{{cite journal | vauthors = Veenman L, Papadopoulos V, Gavish M | title = Channel-like functions of the 18-kDa translocator protein (TSPO): regulation of apoptosis and steroidogenesis as part of the host-defense response | journal = Current Pharmaceutical Design | volume = 13 | issue = 23 | pages = 2385–2405 | year = 2007 | pmid = 17692008 | doi = 10.2174/138161207781368710 }}</ref><ref name="pmid19409385">{{cite journal | vauthors = Papadopoulos V, Lecanu L | title = Translocator protein (18 kDa) TSPO: an emerging therapeutic target in neurotrauma | journal = Experimental Neurology | volume = 219 | issue = 1 | pages = 53–57 | date = September 2009 | pmid = 19409385 | pmc = 2728790 | doi = 10.1016/j.expneurol.2009.04.016 }}</ref><ref name="pmid20407080">{{cite journal | vauthors = Xiao J, Liang D, Zhang H, Liu Y, Li F, Chen YH | title = 4'-Chlorodiazepam, a translocator protein (18 kDa) antagonist, improves cardiac functional recovery during postischemia reperfusion in rats | journal = Experimental Biology and Medicine | volume = 235 | issue = 4 | pages = 478–486 | date = April 2010 | pmid = 20407080 | doi = 10.1258/ebm.2009.009291 | s2cid = 6403616 }}</ref>{{npsn|date=February 2015}}
== See also ==
*[[4'-Chlorodeschloroalprazolam]]
*[[Diclazepam]] (2'-chlorodiazepam)
*[[PK-11195]]
== References ==
{{reflist}}
{{Benzodiazepines}}
{{Translocator protein modulators}}
[[Category:Benzodiazepines]]
[[Category:4-Chlorophenyl compounds]]
[[Category:Designer drugs]]
[[Category:Drugs developed by Hoffmann-La Roche]]
[[Category:Lactams]]
[[Category:TSPO ligands]]
[[Category:Chloroarenes]]
{{sedative-stub}}