“Ro5-4864”的意思、由来-开放百科全书

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 GABA_A 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]{{npsn|date=February 2015}}

1. ^{{cite patent | country = US | number = 3136815}}
2. ^{{cite journal|first1=Kieran R.|last1=Manchester|first2=Peter D.|last2=Maskell|first3=Laura|last3=Waters|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|issn=1942-7611|doi=10.1002/dta.2387|pmid=29582576|date=2018}}
3. ^{{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=157–60 |date=May 1982 |pmid=6287365 |doi= 10.1016/0304-3940(82)90289-0|url=}}
4. ^{{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 |issue= |pages=139–51 |year=1983 |pmid=6670623 |doi= |url=}}
5. ^{{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=93–6 |date=January 1983 |pmid=6682534 |doi= 10.1016/0304-3940(83)90532-3|url=}}
6. ^{{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|url=}}
7. ^{{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=229–40 |date=July 1984 |pmid=6087055 |doi= 10.1016/0024-3205(84)90106-1|url=}}
8. ^{{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 |doi= |url=}}
9. ^{{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=129–37 |date=April 2005 |pmid=15696538 |doi=10.1002/jnr.20430 |url=|hdl=10261/72513 }}
10. ^{{cite journal |vauthors=Leonelli E, Yague JG, Ballabio M, Azcoitia I, Magnaghi V, Schumacher M, Garcia-Segura LM, Melcangi RC |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=1159–63 |date=November 2005 |pmid=16045970 |doi=10.1016/j.mad.2005.06.001 |url=|hdl=10261/72157 }}
11. ^{{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 |url=}}
12. ^{{cite journal |vauthors=Mills C, Makwana M, Wallace A, Benn S, Schmidt H, Tegeder I, Costigan M, Brown RH, Raivich G, Woolf CJ |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=937–46 |date=February 2008 |pmid=18333964 |doi=10.1111/j.1460-9568.2008.06065.x |url=}}
13. ^{{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=201–8 |date=December 2008 |pmid=18789929 |doi=10.1016/j.expneurol.2008.08.008 |url=}}
14. ^{{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 |title=Neuroprotective effects of a ligand of translocator protein-18 kDa (Ro5-4864) in experimental diabetic neuropathy |journal=Neuroscience |volume=164 |issue=2 |pages=520–9 |date=December 2009 |pmid=19665520 |doi=10.1016/j.neuroscience.2009.08.005 |url=|hdl=10261/72515 }}
15. ^{{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=188–94 |date=April 2004 |pmid=15001819 |doi=10.1159/000075547 |url=}}
16. ^{{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=21–6 |date=June 2003 |pmid=12809948 |doi= 10.1016/S0014-2999(03)01789-8|url=}}
17. ^{{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=90–9 |date=January 2015 |pmid=25268650 |doi=10.1016/j.yjmcc.2014.09.024 |pmc=4268014}}
18. ^{{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=336–45 |date=October 2007 |pmid=17640950 |doi=10.1124/jpet.107.124255 |url=}}
19. ^{{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=2385–405 |year=2007 |pmid=17692008 |doi= 10.2174/138161207781368710|url=}}
20. ^{{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=53–7 |date=September 2009 |pmid=19409385 |pmc=2728790 |doi=10.1016/j.expneurol.2009.04.016 |url=}}
21. ^{{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 (Maywood, N.J.) |volume=235 |issue=4 |pages=478–86 |date=April 2010 |pmid=20407080 |doi=10.1258/ebm.2009.009291 |url=}}

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