Ro64-6198 Explained

Verifiedfields:changed
Verifiedrevid:451981063
Iupac Name:8-[(1''S'',3a''S'')-2,3,3a,4,5,6-hexahydro-1''H''-phenalen-1-yl]-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one
Cas Number:280783-56-4
Pubchem:9844019
Iuphar Ligand:1684
Chemspiderid:8019734
Chembl:2088034
C:26
H:31
N:3
O:1
Smiles:C1C[C@H]2CC[C@@H](C3=CC=CC(=C23)C1)N4CCC5(CC4)C(=O)NCN5C6=CC=CC=C6
Stdinchi:1S/C26H31N3O/c30-25-26(29(18-27-25)21-9-2-1-3-10-21)14-16-28(17-15-26)23-13-12-20-7-4-6-19-8-5-11-22(23)24(19)20/h1-3,5,8-11,20,23H,4,6-7,12-18H2,(H,27,30)/t20-,23-/m0/s1
Stdinchikey:JLFMYEAXZNPWBK-REWPJTCUSA-N
Synonyms:Ro64-6198

Ro64-6198 is an opioid drug used in scientific research. It acts as a potent and selective agonist for the nociceptin receptor, also known as the ORL-1 (opiate receptor like-1) receptor, with over 100x selectivity over the other opioid receptors.[1] It produces anxiolytic effects in animal studies equivalent to those of benzodiazepine drugs,[2] but has no anticonvulsant effects and does not produce any overt effects on behaviour.[3] However it does impair short-term memory,[4] and counteracts stress-induced anorexia.[5] [6] It also has antitussive effects,[7] and reduces the rewarding and analgesic effects of morphine, although it did not prevent the development of dependence.[8] [9] [10] It has been shown to reduce alcohol self-administration in animals and suppressed relapses in animal models of alcoholism, and ORL-1 agonists may have application in the treatment of alcoholism.[11]

Ro64-6198 was able to be recognised as a discriminative stimulus by rats distinct from other opioid receptor ligands,[12] but was not able to produce the conditioned place preference thought to be indicative of addictive potential.[13] Consequently, while the role of ORL-1 receptors in the body is complex and remains poorly understood, Ro64-6198 has demonstrated multiple pharmacological actions and has been very useful in the study of the ORL-1 receptor system, especially in relation to anxiety and anorexia; however, due to poor oral bioavailability, Ro 64-6198 will most likely not be pursued clinically.[14] Studies in primates showed it to have analgesic effects but without producing respiratory depression or reinforcing effects.[15]

Notes and References

  1. Dautzenberg FM, Wichmann J, Higelin J, Py-Lang G, Kratzeisen C, Malherbe P, Kilpatrick GJ, Jenck F . 6 . Pharmacological characterization of the novel nonpeptide orphanin FQ/nociceptin receptor agonist Ro 64-6198: rapid and reversible desensitization of the ORL1 receptor in vitro and lack of tolerance in vivo . The Journal of Pharmacology and Experimental Therapeutics . 298 . 2 . 812–819 . August 2001 . 11454946 .
  2. Varty GB, Hyde LA, Hodgson RA, Lu SX, McCool MF, Kazdoba TM, Del Vecchio RA, Guthrie DH, Pond AJ, Grzelak ME, Xu X, Korfmacher WA, Tulshian D, Parker EM, Higgins GA . 6 . Characterization of the nociceptin receptor (ORL-1) agonist, Ro64-6198, in tests of anxiety across multiple species . Psychopharmacology . 182 . 1 . 132–143 . October 2005 . 16025321 . 10.1007/s00213-005-0041-4 . 20493194 .
  3. Jenck F, Wichmann J, Dautzenberg FM, Moreau JL, Ouagazzal AM, Martin JR, Lundstrom K, Cesura AM, Poli SM, Roever S, Kolczewski S, Adam G, Kilpatrick G . 6 . A synthetic agonist at the orphanin FQ/nociceptin receptor ORL1: anxiolytic profile in the rat . Proceedings of the National Academy of Sciences of the United States of America . 97 . 9 . 4938–4943 . April 2000 . 10758169 . 18336 . 10.1073/pnas.090514397 . free . 2000PNAS...97.4938J .
  4. Higgins GA, Kew JN, Richards JG, Takeshima H, Jenck F, Adam G, Wichmann J, Kemp JA, Grottick AJ . 6 . A combined pharmacological and genetic approach to investigate the role of orphanin FQ in learning and memory . The European Journal of Neuroscience . 15 . 5 . 911–922 . March 2002 . 11906533 . 10.1046/j.1460-9568.2002.01926.x . 20973698 .
  5. Ciccocioppo R, Biondini M, Antonelli L, Wichmann J, Jenck F, Massi M . Reversal of stress- and CRF-induced anorexia in rats by the synthetic nociceptin/orphanin FQ receptor agonist, Ro 64-6198 . Psychopharmacology . 161 . 2 . 113–119 . May 2002 . 11981590 . 10.1007/s00213-002-1020-7 . 26808279 .
  6. Ciccocioppo R, Cippitelli A, Economidou D, Fedeli A, Massi M . Nociceptin/orphanin FQ acts as a functional antagonist of corticotropin-releasing factor to inhibit its anorectic effect . Physiology & Behavior . 82 . 1 . 63–68 . August 2004 . 15234592 . 10.1016/j.physbeh.2004.04.035 . 26035134 .
  7. McLeod RL, Jia Y, Fernandez X, Parra LE, Wang X, Tulshian DB, Kiselgof EJ, Tan Z, Fawzi AB, Smith-Torhan A, Zhang H, Hey JA . 6 . Antitussive profile of the NOP agonist Ro-64-6198 in the guinea pig . Pharmacology . 71 . 3 . 143–149 . July 2004 . 15161996 . 10.1159/000077448 . 19512178 .
  8. Kotlinska J, Wichmann J, Rafalski P, Talarek S, Dylag T, Silberring J . Non-peptidergic OP4 receptor agonist inhibits morphine antinociception but does not influence morphine dependence . NeuroReport . 14 . 4 . 601–604 . March 2003 . 12657894 . 10.1097/00001756-200303240-00015 . 25805180 .
  9. Shoblock JR, Wichmann J, Maidment NT . The effect of a systemically active ORL-1 agonist, Ro 64-6198, on the acquisition, expression, extinction, and reinstatement of morphine conditioned place preference . Neuropharmacology . 49 . 4 . 439–446 . September 2005 . 15919100 . 10.1016/j.neuropharm.2005.04.008 . 36459495 .
  10. Reiss D, Wichmann J, Tekeshima H, Kieffer BL, Ouagazzal AM . Effects of nociceptin/orphanin FQ receptor (NOP) agonist, Ro64-6198, on reactivity to acute pain in mice: comparison to morphine . European Journal of Pharmacology . 579 . 1–3 . 141–148 . January 2008 . 18031727 . 10.1016/j.ejphar.2007.10.031 .
  11. Kuzmin A, Kreek MJ, Bakalkin G, Liljequist S . The nociceptin/orphanin FQ receptor agonist Ro 64-6198 reduces alcohol self-administration and prevents relapse-like alcohol drinking . Neuropsychopharmacology . 32 . 4 . 902–910 . April 2007 . 16880770 . 10.1038/sj.npp.1301169 . free .
  12. Recker MD, Higgins GA . The opioid receptor like-1 receptor agonist Ro 64-6198 (1S,3aS-8-2,3,3a,4,5,6-hexahydro-1H-phenalen-1-yl-1-phenyl-1,3,8-triaza-spiro[4.5]decan-4-one) produces a discriminative stimulus in rats distinct from that of a mu, kappa, and delta opioid receptor agonist cue . The Journal of Pharmacology and Experimental Therapeutics . 311 . 2 . 652–658 . November 2004 . 15226383 . 10.1124/jpet.104.071423 . 23849692 .
  13. Le Pen G, Wichmann J, Moreau JL, Jenck F . The orphanin receptor agonist RO 64-6198 does not induce place conditioning in rats . NeuroReport . 13 . 4 . 451–454 . March 2002 . 11930159 . 10.1097/00001756-200203250-00018 . 30616027 .
  14. Shoblock JR . The pharmacology of Ro 64-6198, a systemically active, nonpeptide NOP receptor (opiate receptor-like 1, ORL-1) agonist with diverse preclinical therapeutic activity . CNS Drug Reviews . 13 . 1 . 107–136 . 2007 . 17461893 . 6494153 . 10.1111/j.1527-3458.2007.00007.x .
  15. Ko MC, Woods JH, Fantegrossi WE, Galuska CM, Wichmann J, Prinssen EP . Behavioral effects of a synthetic agonist selective for nociceptin/orphanin FQ peptide receptors in monkeys . Neuropsychopharmacology . 34 . 9 . 2088–2096 . August 2009 . 19279568 . 2804925 . 10.1038/npp.2009.33 .

This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Ro64-6198".

Except where otherwise indicated, Everything.Explained.Today is © Copyright 2009-2024, A B Cryer, All Rights Reserved. Cookie policy.