View source for J-113,397

{{drugbox |
| IUPAC_name        = 1-[(3R,4R)-1-cyclooctylmethyl-3-hydroxymethyl-4-piperidyl]-3-ethyl-1, 3-dihydro-2H-benzimidazol-2-one 
| image             = J-113,397_structure.png
| width             = 200
| CAS_number        = 
| synonyms          = J-113,397
| ATC_prefix        = 
| ATC_suffix        = 
| PubChem           = 5311194
| IUPHAR_ligand = 1691
| DrugBank          = 
| C = 24 | H = 37 | N = 3 | O = 2
| molecular_weight  = 399.568 g/mol
| smiles            = C4CCCCCCC4CN(CC1CO)CCC1n3c2ccccc2n(CC)c3=O
| bioavailability   = 
| protein_bound     = 
| metabolism        = 
| elimination_half-life = 
| excretion         = 
| pregnancy_AU      =  <!-- A / B1 / B2 / B3 / C / D / X -->
| pregnancy_US      =  <!-- A / B            / C / D / X -->
| pregnancy_category=  
| legal_AU          =  <!-- Unscheduled / S2 / S3 / S4 / S5 / S6 / S7 / S8 / S9 -->
| legal_CA          =  
| legal_UK          =  
| legal_US          =  
| legal_status      = 
| routes_of_administration = 
}}

'''J-113,397''' is an [[opioid]] [[analgesic]] drug which was the first compound found to be a highly selective antagonist for the [[nociceptin receptor]], also known as the ORL-1 receptor.<ref>Kawamoto H, Ozaki S, Itoh Y, Miyaji M, Arai S, Nakashima H, Kato T, Ohta H, Iwasawa Y. Discovery of the first potent and selective small molecule opioid receptor-like (ORL1) antagonist: 1-[(3R,4R)-1-cyclooctylmethyl-3- hydroxymethyl-4-piperidyl]-3-ethyl-1, 3-dihydro-2H-benzimidazol-2-one (J-113397). ''Journal of Medicinal Chemistry''. 1999 Dec 16;42(25):5061-3. PMID 10602690</ref><ref>De Risi C, Piero Pollini G, Trapella C, Peretto I, Ronzoni S, Giardina GA. A new synthetic approach to 1-[(3R,4R)-1-cyclooctylmethyl-3-hydroxymethyl-4-piperidyl]-3-ethyl-1,3-dihydro-benzimidazol-2-one(J-113397), the first non-peptide ORL-1 receptor antagonist. ''Bioorganic and Medicinal Chemistry''. 2001 Jul;9(7):1871-7. PMID 11425589</ref> It is several hundred times selective for the ORL-1 receptor over other opioid receptors,<ref>Ozaki S, Kawamoto H, Itoh Y, Miyaji M, Iwasawa Y, Ohta H. A potent and highly selective nonpeptidyl nociceptin/orphanin FQ receptor (ORL1) antagonist: J-113397. ''European Journal of Pharmacology''. 2000 Jan 17;387(3):R17-8. PMID 10650183</ref><ref>Smith ED, Ariane Vinson N, Zhong D, Berrang BD, Catanzaro JL, Thomas JB, Navarro HA, Gilmour BP, Deschamps J, Carroll FI. A new synthesis of the ORL-1 antagonist 1-[(3R,4R)-1-cyclooctylmethyl-3-hydroxymethyl-4-piperidinyl]-3-ethyl-1,3-dihydro-2H-benzimidazol-2-one (J-113397) and activity in a calcium mobilization assay. ''Bioorganic and Medicinal Chemistry''. 2008 Jan 15;16(2):822-9. PMID 17976996</ref> and its effects in animals include preventing the development of [[tachyphylaxis|tolerance]] to [[morphine]]<ref>Chung S, Pohl S, Zeng J, Civelli O, Reinscheid RK. Endogenous orphanin FQ/nociceptin is involved in the development of morphine tolerance. ''Journal of Pharmacology and Experimental Therapeutics''. 2006 Jul;318(1):262-7. PMID 16595734</ref>, the prevention of [[hyperalgesia]] induced by intracerebroventricular administration of nociceptin (orphanin FQ),<ref>Ozaki S, Kawamoto H, Itoh Y, Miyaji M, Azuma T, Ichikawa D, Nambu H, Iguchi T, Iwasawa Y, Ohta H. In vitro and in vivo pharmacological characterization of J-113397, a potent and selective non-peptidyl ORL1 receptor antagonist. ''European Journal of Pharmacology''. 2000 Aug 18;402(1-2):45-53. PMID 10940356</ref> as well as the stimulation of [[dopamine]] release in the [[striatum]],<ref>Marti M, Mela F, Veronesi C, Guerrini R, Salvadori S, Federici M, Mercuri NB, Rizzi A, Franchi G, Beani L, Bianchi C, Morari M. Blockade of nociceptin/orphanin FQ receptor signaling in rat substantia nigra pars reticulata stimulates nigrostriatal dopaminergic transmission and motor behavior. ''Journal of Neuroscience''. 2004 Jul 28;24(30):6659-66. PMID 15282268</ref> which increases the rewarding effects of [[cocaine]],<ref>Marquez P, Nguyen AT, Hamid A, Lutfy K. The endogenous OFQ/N/ORL-1 receptor system regulates the rewarding effects of acute cocaine. ''Neuropharmacology''. 2008 Mar;54(3):564-8. PMID 18082848</ref> but may have clinical application in the treatment of [[Parkinson's disease]].<ref>Marti M, Trapella C, Viaro R, Morari M. The nociceptin/orphanin FQ receptor antagonist J-113397 and L-DOPA additively attenuate experimental parkinsonism through overinhibition of the nigrothalamic pathway. ''Journal of Neuroscience''. 2007 Feb 7;27(6):1297-307. PMID 17287504</ref><ref>Viaro R, Sanchez-Pernaute R, Marti M, Trapella C, Isacson O, Morari M. Nociceptin/orphanin FQ receptor blockade attenuates MPTP-induced parkinsonism. ''Neurobiology of Disease''. 2008 Jun;30(3):430-8. PMID 18413287</ref><ref>Visanji NP, de Bie RM, Johnston TH, McCreary AC, Brotchie JM, Fox SH. The nociceptin/orphanin FQ (NOP) receptor antagonist J-113397 enhances the effects of levodopa in the MPTP-lesioned nonhuman primate model of Parkinson's disease. ''Movement Disorders''. 2008 Oct 15;23(13):1922-5. PMID 18759357</ref>

 

==See also==
* [[JTC-801]]
* [[SB-612,111]]

== References ==
{{reflist}}

{{opioids}}

[[Category:Opioids]]
[[Category:Benzimidazoles]]
[[Category:Piperidines]]
[[Category:Ureas]]
[[Category:Alcohols]]
[[Category:2Fix]]