Page last updated: 2024-11-11

ro 64-6198

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Description

Ro 64-6198: an orphanin FQ/nociceptin receptor agonist; structure in first source [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID9844019
CHEMBL ID2088034
SCHEMBL ID2240259
MeSH IDM0362742

Synonyms (23)

Synonym
8-[(1s,3as)-2,3,3a,4,5,6-hexahydro-1h-phenalen-1-yl]-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one
gtpl1684
ro-646198
ro64-6198
ro646198
ro-64-6198
ro 64-6198
bdbm50420802
CHEMBL2088034 ,
SCHEMBL2240259
(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
280783-56-4
nd1251
Q7339209
DTXSID901018435
CS-0012712
HY-12844
MS-26840
1,3,8-triazaspiro[4.5]decan-4-one, 8-[(1s,3as)-2,3,3a,4,5,6-hexahydro-1h-phenalen-1-yl]-1-phenyl-
hkn6h9xxs6 ,
1,3,8-triazaspiro(4.5)decan-4-one, 8-((1s,3as)-2,3,3a,4,5,6-hexahydro-1h-phenalen-1-yl)-1-phenyl-
8-((1s,3as)-2,3,3a,4,5,6-hexahydro-1h-phenalen-1-yl)-1-phenyl-1,3,8-triazaspiro(4.5)decan-4-one
AKOS040742563

Research Excerpts

Pharmacokinetics

ExcerptReferenceRelevance
" The method was successfully applied to low dose pharmacokinetic studies."( Bioanalytics and pharmacokinetics of the nociceptin/orphanin FQ peptide receptor agonist RO0646198 in Wistar rats and Cynomolgus monkeys.
Bucheli, F; Heinig, K; Kratochwil, N; Thomae, A, 2010
)
0.36

Bioavailability

ExcerptReferenceRelevance
" The bioavailability after oral dosing was below 5% for rats and below 1% in Cynomolgus monkeys, limiting the application of RO0646198 in the clinic to parenteral routes."( Bioanalytics and pharmacokinetics of the nociceptin/orphanin FQ peptide receptor agonist RO0646198 in Wistar rats and Cynomolgus monkeys.
Bucheli, F; Heinig, K; Kratochwil, N; Thomae, A, 2010
)
0.36

Dosage Studied

ExcerptRelevanceReference
" In dose-response studies, Ro64-6198 increased [(35)S]-GTPgammaS binding to a variety of brain regions with EC(50) values ranging from 84."( Distribution of nociceptin and Ro64-6198 activated [35S]-GTPgammaS binding in the rat brain.
Gackenheimer, SL; Gehlert, DR; Shaw, JL, 2006
)
0.33
"), dose-dependently produced rightward shifts of the dose-response curve of Ro 64-6198-induced antinociception."( Behavioral effects of a synthetic agonist selective for nociceptin/orphanin FQ peptide receptors in monkeys.
Fantegrossi, WE; Galuska, CM; Ko, MC; Prinssen, EP; Wichmann, J; Woods, JH, 2009
)
0.58
" The bioavailability after oral dosing was below 5% for rats and below 1% in Cynomolgus monkeys, limiting the application of RO0646198 in the clinic to parenteral routes."( Bioanalytics and pharmacokinetics of the nociceptin/orphanin FQ peptide receptor agonist RO0646198 in Wistar rats and Cynomolgus monkeys.
Bucheli, F; Heinig, K; Kratochwil, N; Thomae, A, 2010
)
0.36
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Protein Targets (4)

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Mu-type opioid receptorHomo sapiens (human)Ki0.40000.00000.419710.0000AID682665
Delta-type opioid receptorHomo sapiens (human)Ki0.40000.00000.59789.9300AID682666
Kappa-type opioid receptorHomo sapiens (human)Ki0.40000.00000.362410.0000AID682664
Nociceptin receptorHomo sapiens (human)Ki0.00110.00000.03370.5000AID682542
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Activation Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Nociceptin receptorHomo sapiens (human)EC50 (µMol)0.02100.00010.00890.0630AID682543
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (59)

Processvia Protein(s)Taxonomy
G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messengerMu-type opioid receptorHomo sapiens (human)
adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathwayMu-type opioid receptorHomo sapiens (human)
phospholipase C-activating G protein-coupled receptor signaling pathwayMu-type opioid receptorHomo sapiens (human)
sensory perceptionMu-type opioid receptorHomo sapiens (human)
negative regulation of cell population proliferationMu-type opioid receptorHomo sapiens (human)
sensory perception of painMu-type opioid receptorHomo sapiens (human)
G protein-coupled opioid receptor signaling pathwayMu-type opioid receptorHomo sapiens (human)
behavioral response to ethanolMu-type opioid receptorHomo sapiens (human)
positive regulation of neurogenesisMu-type opioid receptorHomo sapiens (human)
negative regulation of Wnt protein secretionMu-type opioid receptorHomo sapiens (human)
positive regulation of ERK1 and ERK2 cascadeMu-type opioid receptorHomo sapiens (human)
calcium ion transmembrane transportMu-type opioid receptorHomo sapiens (human)
cellular response to morphineMu-type opioid receptorHomo sapiens (human)
regulation of cellular response to stressMu-type opioid receptorHomo sapiens (human)
regulation of NMDA receptor activityMu-type opioid receptorHomo sapiens (human)
neuropeptide signaling pathwayMu-type opioid receptorHomo sapiens (human)
immune responseDelta-type opioid receptorHomo sapiens (human)
G protein-coupled receptor signaling pathwayDelta-type opioid receptorHomo sapiens (human)
G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messengerDelta-type opioid receptorHomo sapiens (human)
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathwayDelta-type opioid receptorHomo sapiens (human)
phospholipase C-activating G protein-coupled receptor signaling pathwayDelta-type opioid receptorHomo sapiens (human)
adult locomotory behaviorDelta-type opioid receptorHomo sapiens (human)
negative regulation of gene expressionDelta-type opioid receptorHomo sapiens (human)
negative regulation of protein-containing complex assemblyDelta-type opioid receptorHomo sapiens (human)
positive regulation of CREB transcription factor activityDelta-type opioid receptorHomo sapiens (human)
positive regulation of peptidyl-serine phosphorylationDelta-type opioid receptorHomo sapiens (human)
response to nicotineDelta-type opioid receptorHomo sapiens (human)
G protein-coupled opioid receptor signaling pathwayDelta-type opioid receptorHomo sapiens (human)
eating behaviorDelta-type opioid receptorHomo sapiens (human)
regulation of mitochondrial membrane potentialDelta-type opioid receptorHomo sapiens (human)
regulation of calcium ion transportDelta-type opioid receptorHomo sapiens (human)
cellular response to growth factor stimulusDelta-type opioid receptorHomo sapiens (human)
cellular response to hypoxiaDelta-type opioid receptorHomo sapiens (human)
cellular response to toxic substanceDelta-type opioid receptorHomo sapiens (human)
neuropeptide signaling pathwayDelta-type opioid receptorHomo sapiens (human)
immune responseKappa-type opioid receptorHomo sapiens (human)
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathwayKappa-type opioid receptorHomo sapiens (human)
phospholipase C-activating G protein-coupled receptor signaling pathwayKappa-type opioid receptorHomo sapiens (human)
chemical synaptic transmissionKappa-type opioid receptorHomo sapiens (human)
sensory perceptionKappa-type opioid receptorHomo sapiens (human)
locomotory behaviorKappa-type opioid receptorHomo sapiens (human)
sensory perception of painKappa-type opioid receptorHomo sapiens (human)
adenylate cyclase-inhibiting opioid receptor signaling pathwayKappa-type opioid receptorHomo sapiens (human)
response to insulinKappa-type opioid receptorHomo sapiens (human)
positive regulation of dopamine secretionKappa-type opioid receptorHomo sapiens (human)
negative regulation of luteinizing hormone secretionKappa-type opioid receptorHomo sapiens (human)
response to nicotineKappa-type opioid receptorHomo sapiens (human)
G protein-coupled opioid receptor signaling pathwayKappa-type opioid receptorHomo sapiens (human)
maternal behaviorKappa-type opioid receptorHomo sapiens (human)
eating behaviorKappa-type opioid receptorHomo sapiens (human)
response to estrogenKappa-type opioid receptorHomo sapiens (human)
estrous cycleKappa-type opioid receptorHomo sapiens (human)
response to ethanolKappa-type opioid receptorHomo sapiens (human)
regulation of saliva secretionKappa-type opioid receptorHomo sapiens (human)
behavioral response to cocaineKappa-type opioid receptorHomo sapiens (human)
sensory perception of temperature stimulusKappa-type opioid receptorHomo sapiens (human)
defense response to virusKappa-type opioid receptorHomo sapiens (human)
cellular response to lipopolysaccharideKappa-type opioid receptorHomo sapiens (human)
cellular response to glucose stimulusKappa-type opioid receptorHomo sapiens (human)
positive regulation of p38MAPK cascadeKappa-type opioid receptorHomo sapiens (human)
positive regulation of potassium ion transmembrane transportKappa-type opioid receptorHomo sapiens (human)
response to acrylamideKappa-type opioid receptorHomo sapiens (human)
positive regulation of eating behaviorKappa-type opioid receptorHomo sapiens (human)
conditioned place preferenceKappa-type opioid receptorHomo sapiens (human)
neuropeptide signaling pathwayKappa-type opioid receptorHomo sapiens (human)
calcium-mediated signalingNociceptin receptorHomo sapiens (human)
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathwayNociceptin receptorHomo sapiens (human)
phospholipase C-activating G protein-coupled receptor signaling pathwayNociceptin receptorHomo sapiens (human)
sensory perceptionNociceptin receptorHomo sapiens (human)
sensory perception of painNociceptin receptorHomo sapiens (human)
response to estradiolNociceptin receptorHomo sapiens (human)
positive regulation of urine volumeNociceptin receptorHomo sapiens (human)
G protein-coupled opioid receptor signaling pathwayNociceptin receptorHomo sapiens (human)
eating behaviorNociceptin receptorHomo sapiens (human)
negative regulation of cAMP-mediated signalingNociceptin receptorHomo sapiens (human)
estrous cycleNociceptin receptorHomo sapiens (human)
negative regulation of blood pressureNociceptin receptorHomo sapiens (human)
negative regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathwayNociceptin receptorHomo sapiens (human)
regulation of locomotor rhythmNociceptin receptorHomo sapiens (human)
conditioned place preferenceNociceptin receptorHomo sapiens (human)
neuropeptide signaling pathwayNociceptin receptorHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (13)

Processvia Protein(s)Taxonomy
G-protein alpha-subunit bindingMu-type opioid receptorHomo sapiens (human)
G protein-coupled receptor activityMu-type opioid receptorHomo sapiens (human)
beta-endorphin receptor activityMu-type opioid receptorHomo sapiens (human)
voltage-gated calcium channel activityMu-type opioid receptorHomo sapiens (human)
protein bindingMu-type opioid receptorHomo sapiens (human)
morphine receptor activityMu-type opioid receptorHomo sapiens (human)
G-protein beta-subunit bindingMu-type opioid receptorHomo sapiens (human)
neuropeptide bindingMu-type opioid receptorHomo sapiens (human)
G protein-coupled opioid receptor activityDelta-type opioid receptorHomo sapiens (human)
protein bindingDelta-type opioid receptorHomo sapiens (human)
receptor serine/threonine kinase bindingDelta-type opioid receptorHomo sapiens (human)
G protein-coupled enkephalin receptor activityDelta-type opioid receptorHomo sapiens (human)
neuropeptide bindingDelta-type opioid receptorHomo sapiens (human)
G protein-coupled opioid receptor activityKappa-type opioid receptorHomo sapiens (human)
protein bindingKappa-type opioid receptorHomo sapiens (human)
receptor serine/threonine kinase bindingKappa-type opioid receptorHomo sapiens (human)
dynorphin receptor activityKappa-type opioid receptorHomo sapiens (human)
neuropeptide bindingKappa-type opioid receptorHomo sapiens (human)
nociceptin receptor activityNociceptin receptorHomo sapiens (human)
G protein-coupled receptor activityNociceptin receptorHomo sapiens (human)
protein bindingNociceptin receptorHomo sapiens (human)
neuropeptide bindingNociceptin receptorHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (24)

Processvia Protein(s)Taxonomy
endosomeMu-type opioid receptorHomo sapiens (human)
endoplasmic reticulumMu-type opioid receptorHomo sapiens (human)
Golgi apparatusMu-type opioid receptorHomo sapiens (human)
plasma membraneMu-type opioid receptorHomo sapiens (human)
axonMu-type opioid receptorHomo sapiens (human)
dendriteMu-type opioid receptorHomo sapiens (human)
perikaryonMu-type opioid receptorHomo sapiens (human)
synapseMu-type opioid receptorHomo sapiens (human)
plasma membraneMu-type opioid receptorHomo sapiens (human)
neuron projectionMu-type opioid receptorHomo sapiens (human)
plasma membraneDelta-type opioid receptorHomo sapiens (human)
synaptic vesicle membraneDelta-type opioid receptorHomo sapiens (human)
dendrite membraneDelta-type opioid receptorHomo sapiens (human)
presynaptic membraneDelta-type opioid receptorHomo sapiens (human)
axon terminusDelta-type opioid receptorHomo sapiens (human)
spine apparatusDelta-type opioid receptorHomo sapiens (human)
postsynaptic density membraneDelta-type opioid receptorHomo sapiens (human)
neuronal dense core vesicleDelta-type opioid receptorHomo sapiens (human)
plasma membraneDelta-type opioid receptorHomo sapiens (human)
neuron projectionDelta-type opioid receptorHomo sapiens (human)
nucleoplasmKappa-type opioid receptorHomo sapiens (human)
mitochondrionKappa-type opioid receptorHomo sapiens (human)
cytosolKappa-type opioid receptorHomo sapiens (human)
plasma membraneKappa-type opioid receptorHomo sapiens (human)
membraneKappa-type opioid receptorHomo sapiens (human)
sarcoplasmic reticulumKappa-type opioid receptorHomo sapiens (human)
T-tubuleKappa-type opioid receptorHomo sapiens (human)
dendriteKappa-type opioid receptorHomo sapiens (human)
synaptic vesicle membraneKappa-type opioid receptorHomo sapiens (human)
presynaptic membraneKappa-type opioid receptorHomo sapiens (human)
perikaryonKappa-type opioid receptorHomo sapiens (human)
axon terminusKappa-type opioid receptorHomo sapiens (human)
postsynaptic membraneKappa-type opioid receptorHomo sapiens (human)
plasma membraneKappa-type opioid receptorHomo sapiens (human)
neuron projectionKappa-type opioid receptorHomo sapiens (human)
plasma membraneNociceptin receptorHomo sapiens (human)
cytoplasmic vesicleNociceptin receptorHomo sapiens (human)
plasma membraneNociceptin receptorHomo sapiens (human)
neuron projectionNociceptin receptorHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (12)

Assay IDTitleYearJournalArticle
AID682543Agonist activity at human cloned NOP receptor expressed in CHO cell membranes after 30 mins by [35S]GTPgammaS binding assay2012Journal of medicinal chemistry, Jun-14, Volume: 55, Issue:11
Development of LC-MS/MS-based receptor occupancy tracers and positron emission tomography radioligands for the nociceptin/orphanin FQ (NOP) receptor.
AID682666Displacement of [3H]diprenorphine from human cloned delta type opioid receptor expressed in CHO cell membranes by scintillation counter2012Journal of medicinal chemistry, Jun-14, Volume: 55, Issue:11
Development of LC-MS/MS-based receptor occupancy tracers and positron emission tomography radioligands for the nociceptin/orphanin FQ (NOP) receptor.
AID749832Selectivity for human nociceptin receptor over human mu opioid receptor2013Bioorganic & medicinal chemistry letters, Jun-01, Volume: 23, Issue:11
Designing bifunctional NOP receptor-mu opioid receptor ligands from NOP receptor-selective scaffolds. Part I.
AID682536Lipophilicity, log D of the compound at pH 7.4 by potentiometric method2012Journal of medicinal chemistry, Jun-14, Volume: 55, Issue:11
Development of LC-MS/MS-based receptor occupancy tracers and positron emission tomography radioligands for the nociceptin/orphanin FQ (NOP) receptor.
AID682542Displacement of [3H]Nociceptin from human recombinant NOP receptor expressed in CHO cells by scintillation counter2012Journal of medicinal chemistry, Jun-14, Volume: 55, Issue:11
Development of LC-MS/MS-based receptor occupancy tracers and positron emission tomography radioligands for the nociceptin/orphanin FQ (NOP) receptor.
AID749830Selectivity for human nociceptin receptor over human kappa opioid receptor2013Bioorganic & medicinal chemistry letters, Jun-01, Volume: 23, Issue:11
Designing bifunctional NOP receptor-mu opioid receptor ligands from NOP receptor-selective scaffolds. Part I.
AID749831Selectivity for human nociceptin receptor over human delta opioid receptor2013Bioorganic & medicinal chemistry letters, Jun-01, Volume: 23, Issue:11
Designing bifunctional NOP receptor-mu opioid receptor ligands from NOP receptor-selective scaffolds. Part I.
AID682662Agonist activity at human cloned NOP receptor expressed in CHO cell membranes after 30 mins by [35S]GTPgammaS binding assay relative to nociceptin2012Journal of medicinal chemistry, Jun-14, Volume: 55, Issue:11
Development of LC-MS/MS-based receptor occupancy tracers and positron emission tomography radioligands for the nociceptin/orphanin FQ (NOP) receptor.
AID682665Displacement of [3H]diprenorphine from human cloned mu type opioid receptor expressed in CHO cell membranes by scintillation counter2012Journal of medicinal chemistry, Jun-14, Volume: 55, Issue:11
Development of LC-MS/MS-based receptor occupancy tracers and positron emission tomography radioligands for the nociceptin/orphanin FQ (NOP) receptor.
AID682664Displacement of [3H]diprenorphine from human cloned kappa type opioid receptor expressed in CHO cell membranes by scintillation counter2012Journal of medicinal chemistry, Jun-14, Volume: 55, Issue:11
Development of LC-MS/MS-based receptor occupancy tracers and positron emission tomography radioligands for the nociceptin/orphanin FQ (NOP) receptor.
AID1346299Human NOP receptor (Opioid receptors)2000Proceedings of the National Academy of Sciences of the United States of America, Apr-25, Volume: 97, Issue:9
A synthetic agonist at the orphanin FQ/nociceptin receptor ORL1: anxiolytic profile in the rat.
AID1346299Human NOP receptor (Opioid receptors)2000European journal of medicinal chemistry, Sep, Volume: 35, Issue:9
Synthesis of (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, a potent and selective orphanin FQ (OFQ) receptor agonist with anxiolytic-like properties.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (54)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's0 (0.00)18.2507
2000's31 (57.41)29.6817
2010's21 (38.89)24.3611
2020's2 (3.70)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 11.76

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be weak demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index11.76 (24.57)
Research Supply Index4.01 (2.92)
Research Growth Index5.77 (4.65)
Search Engine Demand Index0.00 (26.88)
Search Engine Supply Index0.00 (0.95)

This Compound (11.76)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials0 (0.00%)5.53%
Reviews4 (7.41%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other50 (92.59%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]