Cognitive & Neuroprotection

Nociceptin

Nociceptin is seventeen amino acids that look like an opioid and bind a receptor built like an opioid receptor — the nociceptin opioid peptide receptor, or NOP — with one exception that defines it: naloxone, the overdose-reversal drug that blocks every other opioid receptor, does not touch this one. Its effects are contradictory enough that the pharmaceutical industry has largely pursued blockers of it instead, and the human trials on file are all of an oral NOP antagonist, LY2940094, in depression and in receptor imaging. Where nociceptin itself appears in human data it is being measured rather than given: people with migraine carry lower blood levels than controls, lower still during an attack, which is an association waiting for someone to test the direction.

Last updated 12 August 2026

Studied forPain modulation research · Mood and anxiety research · Bladder overactivity research

Evidence on file1 in-vitro study · 2 citations not yet graded

Strongest sourceStructure of the nociceptin/orphanin FQ receptor in complex with a peptide mimetic (Nature 2012, cited 421x) (in-vitro study)

Mechanism

Activates the Gi-coupled NOP receptor, structurally an opioid receptor but insensitive to naloxone, damping neuronal excitability.

Reported effects

What sources associate with this compound. Reported categories, not outcomes we have graded — each would need its own citation and rung.

Pain modulation research
Mood and anxiety research
Bladder overactivity research

Dosing on file unverified

Intravesical: 1 mg/10mL or 1 µM; Oral antagonist LY2940094: 40 mg daily; NOP receptor agonist: Phase I (90 subjects)

Carried from a source that labels it unverified, and reproduced with that label attached. A record of what is reported, not a recommendation. No citation on this page establishes it.

Literature on file 4

in vitro
Structure of the nociceptin/orphanin FQ receptor in complex with a peptide mimetic (Nature 2012, cited 421x) graded on: X-ray crystal structure of human NOP with a peptide-mimetic antagonist; cell-free — read from the abstract — “abstract review”
review or editorial
Pharmacology of nociceptin and its receptor: a novel therapeutic target (British Journal of Pharmacology 2000, cited 376x) graded on: indexed as "review-article" - secondary literature, not a study — “review-article”

Not graded

2 citations whose study design could not be read from the title. Left ungraded rather than guessed at.

not graded
NCT01404091: Assessment of Nociceptin/Orphanin FQ Peptide Receptor Occupancy After Single Oral Doses of LY2940094 as Measured by Positron Emission Tomography With the Radioligand LY2959530 in Healthy Subjects graded on: NCT01404091 is completed and has posted no results - a registration, not a reported outcome — “NCT01404091”
not graded
NCT06786637: A Combined Investigation of the Protective Impact of the NOF/Q Antagonist LY-2940094 on Stress-induced Depression- and Anxiety-related Phenotypes in Humans graded on: NCT06786637 is withdrawn and has posted no results - a registration, not a reported outcome — “NCT06786637”

Identity

Space-filling 3D model of Nociceptin, carbon grey, nitrogen blue, oxygen red — Built from the SMILES on this record — the atoms and bonds are exact. The shape is **one computed low-energy pose**, not a measured structure: a flexible peptide in solution has no single conformation, and where the SMILES leaves a stereocentre undefined the pose commits to one arbitrarily. The skeletal formula below claims connectivity and nothing more, which is what we actually know.

2D chemical structure of Nociceptin — Built from the SMILES on this record — the atoms and bonds are exact. The shape is **one computed low-energy pose**, not a measured structure: a flexible peptide in solution has no single conformation, and where the SMILES leaves a stereocentre undefined the pose commits to one arbitrarily. The skeletal formula below claims connectivity and nothing more, which is what we actually know.

Molecular weight: 1809.0
Molecular formula: C79H129N27O22
CAS number: 170713-75-4
PubChem CID: 16131448
InChI key: PULGYDLMFSFVBL-SMFNREODSA-N
SMILES: C[C@H]([C@@H](C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CCC(=O)N)C(=O)O)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)CNC(=O)CNC(=O)[C@H](CC2=CC=CC=C2)N)O
InChI: InChI=1S/C79H129N27O22/c1-41(2)33-54(72(122)95-44(5)66(116)103-56(36-59(84)110)73(123)102-53(77(127)128)27-28-58(83)109)104-70(120)49(23-13-15-29-80)100-69(119)52(26-18-32-90-79(87)88)99-65(115)43(4)96-75(125)57(40-107)105-71(121)50(24-14-16-30-81)101-68(118)51(25-17-31-89-78(85)86)98-64(114)42(3)94-61(112)39-93-76(126)63(45(6)108)106-74(124)55(35-47-21-11-8-12-22-47)97-62(113)38-91-60(111)37-92-67(117)48(82)34-46-19-9-7-10-20-46/h7-12,19-22,41-45,48-57,63,107-108H,13-18,23-40,80-82H2,1-6H3,(H2,83,109)(H2,84,110)(H,91,111)(H,92,117)(H,93,126)(H,94,112)(H,95,122)(H,96,125)(H,97,113)(H,98,114)(H,99,115)(H,100,119)(H,101,118)(H,102,123)(H,103,116)(H,104,120)(H,105,121)(H,106,124)(H,127,128)(H4,85,86,89)(H4,87,88,90)/t42-,43-,44-,45+,48-,49-,50-,51-,52-,53-,54-,55-,56-,57-,63-/m0/s1

Notes unverified prose

NCT01404091: 40 mg LY2940094 oral; NCT06786637: 40 mg LY2940094 for depression; intravesical N/OFQ 1mg/10mL for IC/PBS; Phase I NOP agonist (Grünenthal); LY2940094 (NOP antagonist)

Not on file 2

1 of the 8 fields we track hold nothing on this record, and each says why. 1 further absence is named below. A blank field is a bug; a named absence is a finding.

amino-acid sequencenothing we hold supplies it
half-lifenothing we hold supplies it

Each field links to every other record missing the same thing. The full ledger holds 765 gaps across 163 records.