Chemistry:Ro64-6198
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| Other names | Ro64-6198 |
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| Formula | C26H31N3O |
| Molar mass | 401.554 g·mol−1 |
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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]
References
- ↑ "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. PMID 11454946. http://jpet.aspetjournals.org/content/298/2/812.full.
- ↑ "Characterization of the nociceptin receptor (ORL-1) agonist, Ro64-6198, in tests of anxiety across multiple species". Psychopharmacology 182 (1): 132–143. October 2005. doi:10.1007/s00213-005-0041-4. PMID 16025321.
- ↑ "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. doi:10.1073/pnas.090514397. PMID 10758169. Bibcode: 2000PNAS...97.4938J.
- ↑ "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. doi:10.1046/j.1460-9568.2002.01926.x. PMID 11906533.
- ↑ "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. doi:10.1007/s00213-002-1020-7. PMID 11981590.
- ↑ "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. doi:10.1016/j.physbeh.2004.04.035. PMID 15234592.
- ↑ "Antitussive profile of the NOP agonist Ro-64-6198 in the guinea pig". Pharmacology 71 (3): 143–149. July 2004. doi:10.1159/000077448. PMID 15161996.
- ↑ "Non-peptidergic OP4 receptor agonist inhibits morphine antinociception but does not influence morphine dependence". NeuroReport 14 (4): 601–604. March 2003. doi:10.1097/00001756-200303240-00015. PMID 12657894.
- ↑ "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. doi:10.1016/j.neuropharm.2005.04.008. PMID 15919100.
- ↑ "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. doi:10.1016/j.ejphar.2007.10.031. PMID 18031727.
- ↑ "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. doi:10.1038/sj.npp.1301169. PMID 16880770.
- ↑ "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. doi:10.1124/jpet.104.071423. PMID 15226383.
- ↑ "The orphanin receptor agonist RO 64-6198 does not induce place conditioning in rats". NeuroReport 13 (4): 451–454. March 2002. doi:10.1097/00001756-200203250-00018. PMID 11930159.
- ↑ "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. doi:10.1111/j.1527-3458.2007.00007.x. PMID 17461893.
- ↑ "Behavioral effects of a synthetic agonist selective for nociceptin/orphanin FQ peptide receptors in monkeys". Neuropsychopharmacology 34 (9): 2088–2096. August 2009. doi:10.1038/npp.2009.33. PMID 19279568.
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