Ro5-4864

{{Short description|Chemical compound}}

{{Drugbox

| Verifiedfields = changed

| Watchedfields = changed

| verifiedrevid = 451564612

| IUPAC_name = 7-Chloro-5-(4-chlorophenyl)-1-methyl-3H-1,4-benzodiazepin-2-one

| image = Ro5-4864.svg

| image_class = skin-invert-image

| width = 177

| tradename =

| legal_CA = Schedule IV

| legal_DE = NpSG

| legal_UK = PSA

| legal_US = Not FDA approved

| bioavailability =

| metabolism =

| elimination_half-life =

| excretion =

| 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

| 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{{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 }} (4'-chlorodiazepam) is a drug which is a benzodiazepine derivative of diazepam.{{cite journal | vauthors = Manchester KR, Maskell PD, Waters L | title = Experimental versus theoretical log D_7.4 , pK_a 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://pure.hud.ac.uk/ws/files/13273614/logDpKaPPB_13thMar2018.pdf }} However unlike most benzodiazepine derivatives, Ro5-4864 lacks affinity for GABA_A receptors and lacks typical benzodiazepine effects,{{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 }} instead being sedative yet also convulsant and anxiogenic in effects.{{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 }}{{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 }}{{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 }}{{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 }} Ro5-4864 was found to be a potent ligand for the "peripheral benzodiazepine receptor",{{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 }} 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.{{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 }}{{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 }}{{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 }}{{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 }}{{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 }}{{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 }} In vitro studies and rodent models also suggest the possibility of analgesic,{{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 }} antidepressant,{{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 }} cardioprotective,{{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 }} and anti-cancer effects.{{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 }}{{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 }}{{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 }}{{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 }}{{npsn|date=February 2015}}