オピオイドペプチド

WordNet

amide combining the amino group of one amino acid with the carboxyl group of another; usually obtained by partial hydrolysis of protein

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2017/12/22 16:35:09」(JST)

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Structural correlation between met-enkephalin, an opioid peptide, (left) and morphine, an opiate drug, (right)

Opioid peptides are peptides that bind to opioid receptors in the brain; opiates and opioids mimic the effect of these peptides. Such peptides may be produced by the body itself, for example endorphins. The effects of these peptides vary, but they all resemble those of opiates. Brain opioid peptide systems are known to play an important role in motivation, emotion, attachment behaviour, the response to stress and pain, and the control of food intake.

Opioid-like peptides may also be absorbed from partially digested food (casomorphins, exorphins, and rubiscolins). The opioid food peptides have lengths of typically 4–8 amino acids. The body's own opioids are generally much longer.

Opioid peptides are released by post-translational proteolytic cleavage of precursor proteins. The precursors consist of the following components: a signal sequence that precedes a conserved region of about 50 residues; a variable-length region; and the sequence of the neuropeptides themselves. Sequence analysis reveals that the conserved N-terminal region of the precursors contains 6 cysteines, which are probably involved in disulfide bond formation. It is speculated that this region might be important for neuropeptide processing.^[1]

Endogenous opioids produced in the body

The human genome contains several homologous genes that are known to code for endogenous opioid peptides.

The nucleotide sequence of the human gene for proopiomelanocortin (POMC) was characterized in 1980.^[2] The POMC gene codes for endogenous opioids such as β-endorphin and γ-endorphin.^[3]
The human gene for the enkephalins was isolated and its sequence described in 1982.^[4]
The human gene for dynorphins (originally called the "Enkephalin B" gene because of sequence similarity to the enkephalin gene) was isolated and its sequence described in 1983.^[5]
The PNOC gene encoding prepronociceptin, which is cleaved into nociceptin and potentially two additional neuropeptides.^[1]
Adrenorphin, amidorphin, and leumorphin were discovered in the 1980s.
The endomorphins were discovered in the 1990s.
Opiorphin and spinorphin, enkephalinase inhibitors (i.e., prevent the metabolism of enkephalins).
Hemorphins, hemoglobin-derived opioid peptides, including hemorphin-4, valorphin, and spinorphin, among others.

While not peptides, codeine and morphine are also produced in the human body.^[6]

Endogenous opioid peptides and their receptors
Opioid peptide	Amino acid sequence	Opioid receptor target(s)	References
Enkephalins
Leu-enkephalin	YGGFL	δ-opioid receptor, μ-opioid receptor	^[7]^[8]
Met-enkephalin	YGGFM	μ-opioid receptor, δ-opioid receptor	^[7]^[8]
Metorphamide	YGGFMRRV-NH₂	δ-opioid receptor, μ-opioid receptor	^[7]
Peptide E	YGGFMRRVGRPEWWMDYQKRYGGFL	μ-opioid receptor, κ-opioid receptor	^[7]
Endorphins
α-Endorphin	YGGFMTSEKSQTPLVT	μ-opioid receptor, unknown affinity for other opioid receptors	^[7]
β-Endorphin	YGGFMTSEKSQTPLVTLFKNAIIKNAYKKGE	μ-opioid receptor, δ-opioid receptor	^[7]^[8]
γ-Endorphin	YGGFMTSEKSQTPLVTL	μ-opioid receptor, unknown affinity for other opioid receptors	^[7]
Dynorphins
Dynorphin A	YGGFLRRIRPKLKWDNQ	κ-opioid receptor	^[7]^[8]
Dynorphin A_1–8	YGGFLRRI	κ-opioid receptor, μ-opioid receptor (partial agonist at δ-opioid receptor)	^[9]^[10]
Dynorphin B	YGGFLRRQFKVVT	κ-opioid receptor	^[7]^[8]
Big dynorphin	YGGFLRRIRPKLKWDNQKRYGGFLRRQFKVVT	κ-opioid receptor	^[11]^[12]
α-Neoendorphin	YGGFLRKYPK	κ-opioid receptor	^[7]^[8]
β-Neoendorphin	YGGFLRKYP	κ-opioid receptor	^[7]
Nociceptin
Nociceptin	FGGFTGARKSARKLANQ	nociceptin receptor	^[7]^[8]
Endomorphins
Endomorphin-1	YPWF-NH₂	μ-opioid receptor	^[7]^[8]
Endomorphin-2	YPFF-NH₂	μ-opioid receptor	^[7]^[8]
Dermal peptides
Dermorphin	YaFGYPS-NH₂	μ-opioid receptor	^[7]
Deltorphin A	YmFHLMD	δ-opioid receptor	^[7]
Deltorphin C	YaFDVVG-NH₂	δ-opioid receptor	^[7]

Opioid food peptides

Casomorphin (from casein found in milk of mammals, including cows)
Gluten exorphin (from gluten found in wheat, rye, barley)
Gliadorphin/gluteomorphin (from gluten found in wheat, rye, barley)
Soymorphin-5 (from soybean)
Rubiscolin (from spinach)

Amphibian opioid peptides

Deltorphin
Deltorphin I
Deltorphin II
Dermorphin

Synthetic opioid peptides

Zyklophin – semisynthetic KOR antagonist derived from dynorphin A

References

^ ^a ^b Mollereau C, Simons MJ, Soularue P, Liners F, Vassart G, Meunier JC, Parmentier M (August 1996). "Structure, tissue distribution, and chromosomal localization of the prepronociceptin gene". Proc. Natl. Acad. Sci. U.S.A. 93 (16): 8666–70. doi:10.1073/pnas.93.16.8666. PMC 38730 . PMID 8710928.
^ Chang AC, Cochet M, Cohen SN (August 1980). "Structural organization of human genomic DNA encoding the pro-opiomelanocortin peptide". Proc. Natl. Acad. Sci. U.S.A. 77 (8): 4890–4. doi:10.1073/pnas.77.8.4890. PMC 349954 . PMID 6254047.
^ Ling N, Burgus R, Guillemin R (November 1976). "Isolation, primary structure, and synthesis of alpha-endorphin and gamma-endorphin, two peptides of hypothalamic-hypophysial origin with morphinomimetic activity". Proc. Natl. Acad. Sci. U.S.A. 73 (11): 3942–6. doi:10.1073/pnas.73.11.3942. PMC 431275 . PMID 1069261.
^ Noda M, Teranishi Y, Takahashi H, Toyosato M, Notake M, Nakanishi S, Numa S (June 1982). "Isolation and structural organization of the human preproenkephalin gene". Nature. 297 (5865): 431–4. doi:10.1038/297431a0. PMID 6281660.
^ Horikawa S, Takai T, Toyosato M, Takahashi H, Noda M, Kakidani H, et al. (Dec 1983). "Isolation and structural organization of the human preproenkephalin B gene". Nature. 306 (5943): 611–4. doi:10.1038/306611a0. PMID 6316163.
^ Stefano GB, Ptáček R, Kuželová H, Kream RM (2012). "Endogenous morphine: up-to-date review 2011" (PDF). Folia Biol. (Praha). 58 (2): 49–56. PMID 22578954. Positive evolutionary pressure has apparently preserved the ability to synthesize chemically authentic morphine, albeit in homeopathic concentrations, throughout animal phyla. ... The apparently serendipitous finding of an opiate alkaloid-sensitive, opioid peptide-insensitive, µ3 opiate receptor subtype expressed by invertebrate immunocytes, human blood monocytes, macrophage cell lines, and human blood granulocytes provided compelling validating evidence for an autonomous role of endogenous morphine as a biologically important cellular signalling molecule (Stefano et al., 1993; Cruciani et al., 1994; Stefano and Scharrer, 1994; Makman et al., 1995). ... Human white blood cells have the ability to make and release morphine
^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l ^m ⁿ ^o ^p ^q Li Y, Lefever MR, Muthu D, Bidlack JM, Bilsky EJ, Polt R (February 2012). "Opioid glycopeptide analgesics derived from endogenous enkephalins and endorphins". Future Medicinal Chemistry. 4 (2): 205–226. doi:10.4155/fmc.11.195. PMC 3306179 . PMID 22300099. Table 1: Endogenous opioid peptides
^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ Toll L, Caló G, Cox BM, Chavkin C, Christie MJ, Civelli O, Connor M, Devi LA, Evans C, Henderson G, Höllt V, Kieffer B, Kitchen I, Kreek MJ, Liu-Chen LY, Meunier JC, Portoghese PS, Shippenberg TS, Simon EJ, Traynor JR, Ueda H, Wong YH (10 August 2015). "Opioid receptors: Introduction". IUPHAR/BPS Guide to PHARMACOLOGY. International Union of Basic and Clinical Pharmacology. Retrieved 20 October 2017.
^ "Dynorphin A 1-8". HMDB Version 4.0. Human Metabolome Database. 27 September 2017. Retrieved 20 October 2017. Dynorphin A (1-8) is a fraction of Dynorphin A with only Tyr-Gly-Gly-Phe-Leu-Arg-Arg-Ile peptide chain.
^ "Dynorphin A-(1-8): Biological activity". IUPHAR/BPS Guide to PHARMACOLOGY. International Union of Basic and Clinical Pharmacology. Retrieved 20 October 2017. Principal endogenous agonists at κ receptor
^ "Big dynorphin: Biological activity". IUPHAR/BPS Guide to PHARMACOLOGY. International Union of Basic and Clinical Pharmacology. Retrieved 20 October 2017. Principal endogenous agonists at κ receptor
^ "Big dynorphin: Structure – Peptide Sequence". IUPHAR/BPS Guide to PHARMACOLOGY. International Union of Basic and Clinical Pharmacology. Retrieved 20 October 2017. Peptide sequence
YGGFLRRIRPKLKWDNQKRYGGFLRRQFKVVT

External links

Opioid Peptides at the US National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the public domain Pfam and InterPro IPR006024

UpToDate Contents

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1. 思春期におけるオピオイド離脱 opioid withdrawal in adolescents
2. オピオイド使用障害の薬物療法 pharmacotherapy for opioid use disorder
3. オピオイド系薬剤を用いた癌疼痛のマネージメント：至適鎮痛作用 cancer pain management with opioids optimizing analgesia
4. 成人における急性オピオイド中毒 acute opioid intoxication in adults
5. オピオイド使用障害：疫学、薬理学、臨床症状、経過、スクリーニング、評価、および診断 opioid use disorder epidemiology pharmacology clinical manifestations course screening assessment and diagnosis

English Journal

Transepithelial transport of milk derived bioactive peptide VLPVPQK.

Vij R1, Reddi S2, Kapila S3, Kapila R4.
Food chemistry.Food Chem.2016 Jan 1;190:681-8. doi: 10.1016/j.foodchem.2015.05.121. Epub 2015 Jun 6.
The transepithelial transport of an antioxidative and ACE inhibitory peptide, VLPVPQK (named peptide C) derived from casein hydrolysates was investigated along with extensively studied opioid peptide β-casomorphin using a human intestinal cell (Caco-2) monolayer. The susceptibility to the brush-bor
PMID 26213026

Regulation of nonsmall-cell lung cancer stem cell like cells by neurotransmitters and opioid peptides.

Banerjee J1, Papu John AM1, Schuller HM1.
International journal of cancer. Journal international du cancer.Int J Cancer.2015 Dec 15;137(12):2815-24. doi: 10.1002/ijc.29646. Epub 2015 Jul 2.
Nonsmall-cell lung cancer (NSCLC) is the leading type of lung cancer and has a poor prognosis. We have shown that chronic stress promoted NSCLC xenografts in mice via stress neurotransmitter-activated cAMP signaling downstream of beta-adrenergic receptors and incidental beta-blocker therapy was repo
PMID 26088878

The Epigenetic Regulation of the Opioid System: New Individualized Prompt Prevention and Treatment Strategies.

Muñoa I1, Urizar I1, Casis L1, Irazusta J1, Subirán N1.
Journal of cellular biochemistry.J Cell Biochem.2015 Nov;116(11):2419-26. doi: 10.1002/jcb.25222.
The most well-known physiological effect associated with opiod system is their efficacy in pain reduction or analgesia, although their effect on a variety of other physiological and physiophological functions has become apparent in recent years. This review is an attempt to clarify in more detail th
PMID 25974312

Japanese Journal

長鎖脂肪酸受容体G protein-coupled receptor 40 (GPR40) を介した docosahexaenoic acid (DHA) の抗侵害作用機構

中本賀寿夫,西中崇,里尚也,万倉三正,小山豊,徳山尚吾
YAKUGAKU ZASSHI 134(3), 397-403, 2014
… Recently, we have also demonstrated that the release of an endogenous opioid peptide, β-endorphin, plays an important role in the induction of docosahexaenoic acid (DHA)-induced antinociception. …
NAID 130003391182

Antihyperalgesic Effect of Buprenorphine Involves Nociceptin/Orphanin FQ Peptide–Receptor Activation in Rats With Spinal Nerve Injury–Induced Neuropathy

Takahashi Tomoko,Okubo Kazumasa,Kojima Shota [他],Nishikawa Hiroyuki,Takemura Motohide,Tsubota-Matsunami Maho,Sekiguchi Fumiko,Kawabata Atsufumi
Journal of Pharmacological Sciences 122(1), 51-54, 2013
… We evaluated the effect of buprenorphine, a mixed agonist for μ-opioid receptors and nociceptin/orphanin FQ peptide (NOP) receptors, in neuropathic rats, using the paw pressure test. … Together, buprenorphine suppresses neuropathic hyperalgesia by activating NOP and opioid receptors, suggesting its therapeutic usefulness in treatment of neuropathic pain. …
NAID 130003362701

Functional Analysis of a Histidine Residue Essential for Receptor Activation of Delta Opioid Receptor

ABE Yoshinori,MATSUO Takashi,NISHIMURA Hirokazu,LI Jinglan,NOSE Takeru,COSTA Tommaso,SHIMOHIGASHI Yasuyuki
Peptide
NAID 10030204235

「オピオイドペプチド」

Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary

Vertebrate endogenous opioids neuropeptide
Identifiers
Symbol	Opiods_neuropep
Pfam	PF01160
InterPro	IPR006024
PROSITE	PDOC00964
Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary

　　[★]

英: opioid peptide, opioid peptides
同: 内因性モルヒネ様物質 endogenous morphine like substance

「opioid peptides」

　　[★] オピオイドペプチド

「opioid」

　　[★] オピオイド

同: opioids

[pmid8710928-1] Mollereau C, Simons MJ, Soularue P, Liners F, Vassart G, Meunier JC, Parmentier M (August 1996). "Structure, tissue distribution, and chromosomal localization of the prepronociceptin gene". Proc. Natl. Acad. Sci. U.S.A. 93 (16): 8666–70. doi:10.1073/pnas.93.16.8666. PMC 38730 . PMID 8710928.

[2] Chang AC, Cochet M, Cohen SN (August 1980). "Structural organization of human genomic DNA encoding the pro-opiomelanocortin peptide". Proc. Natl. Acad. Sci. U.S.A. 77 (8): 4890–4. doi:10.1073/pnas.77.8.4890. PMC 349954 . PMID 6254047.

[3] Ling N, Burgus R, Guillemin R (November 1976). "Isolation, primary structure, and synthesis of alpha-endorphin and gamma-endorphin, two peptides of hypothalamic-hypophysial origin with morphinomimetic activity". Proc. Natl. Acad. Sci. U.S.A. 73 (11): 3942–6. doi:10.1073/pnas.73.11.3942. PMC 431275 . PMID 1069261.

[4] Noda M, Teranishi Y, Takahashi H, Toyosato M, Notake M, Nakanishi S, Numa S (June 1982). "Isolation and structural organization of the human preproenkephalin gene". Nature. 297 (5865): 431–4. doi:10.1038/297431a0. PMID 6281660.

[5] Horikawa S, Takai T, Toyosato M, Takahashi H, Noda M, Kakidani H, et al. (Dec 1983). "Isolation and structural organization of the human preproenkephalin B gene". Nature. 306 (5943): 611–4. doi:10.1038/306611a0. PMID 6316163.

[Endogenous_morphine_in_humans-6] Stefano GB, Ptáček R, Kuželová H, Kream RM (2012). "Endogenous morphine: up-to-date review 2011" (PDF). Folia Biol. (Praha). 58 (2): 49–56. PMID 22578954. Positive evolutionary pressure has apparently preserved the ability to synthesize chemically authentic morphine, albeit in homeopathic concentrations, throughout animal phyla. ... The apparently serendipitous finding of an opiate alkaloid-sensitive, opioid peptide-insensitive, µ3 opiate receptor subtype expressed by invertebrate immunocytes, human blood monocytes, macrophage cell lines, and human blood granulocytes provided compelling validating evidence for an autonomous role of endogenous morphine as a biologically important cellular signalling molecule (Stefano et al., 1993; Cruciani et al., 1994; Stefano and Scharrer, 1994; Makman et al., 1995). ... Human white blood cells have the ability to make and release morphine

[Endogenous_opioid_families_-_2012_review-7] ^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l ^m ⁿ ^o ^p ^q Li Y, Lefever MR, Muthu D, Bidlack JM, Bilsky EJ, Polt R (February 2012). "Opioid glycopeptide analgesics derived from endogenous enkephalins and endorphins". Future Medicinal Chemistry. 4 (2): 205–226. doi:10.4155/fmc.11.195. PMC 3306179 . PMID 22300099. Table 1: Endogenous opioid peptides

[IUPHAR_Opioid_receptors_-_Introduction-8] ^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ Toll L, Caló G, Cox BM, Chavkin C, Christie MJ, Civelli O, Connor M, Devi LA, Evans C, Henderson G, Höllt V, Kieffer B, Kitchen I, Kreek MJ, Liu-Chen LY, Meunier JC, Portoghese PS, Shippenberg TS, Simon EJ, Traynor JR, Ueda H, Wong YH (10 August 2015). "Opioid receptors: Introduction". IUPHAR/BPS Guide to PHARMACOLOGY. International Union of Basic and Clinical Pharmacology. Retrieved 20 October 2017.

[HMDB_Dynorphin_A_1-8-9] "Dynorphin A 1-8". HMDB Version 4.0. Human Metabolome Database. 27 September 2017. Retrieved 20 October 2017. Dynorphin A (1-8) is a fraction of Dynorphin A with only Tyr-Gly-Gly-Phe-Leu-Arg-Arg-Ile peptide chain.

[IUPHAR_-_Dynorphin_A-(1-8)_-_Biological_activity-10] "Dynorphin A-(1-8): Biological activity". IUPHAR/BPS Guide to PHARMACOLOGY. International Union of Basic and Clinical Pharmacology. Retrieved 20 October 2017. Principal endogenous agonists at κ receptor

[IUPHAR_-_Big_dynorphin_-_Biological_activity-11] "Big dynorphin: Biological activity". IUPHAR/BPS Guide to PHARMACOLOGY. International Union of Basic and Clinical Pharmacology. Retrieved 20 October 2017. Principal endogenous agonists at κ receptor

[IUPHAR_-_Big_dynorphin_-_Structure-12] "Big dynorphin: Structure – Peptide Sequence". IUPHAR/BPS Guide to PHARMACOLOGY. International Union of Basic and Clinical Pharmacology. Retrieved 20 October 2017. Peptide sequence
YGGFLRRIRPKLKWDNQKRYGGFLRRQFKVVT

v t e Opioid receptor modulators
MOR	Agonists (abridged; see here for a full list): 3-HO-PCP 7-Acetoxymitragynine 7-Hydroxymitragynine ψ-Akuammigine α-Chlornaltrexamine α-Narcotine Acetyldihydrocodeine Acetylfentanyl Acrylfentanyl Adrenorphin (metorphamide) AH-7921 Akuammicine Akuammidine Alfentanil Anileridine Apparicine β-Endorphin BAM-12P BAM-18P BAM-22P Benzhydrocodone Benzylmorphine Bezitramide Biphalin BU08070 Buprenorphine Butorphan Butorphanol Butyrfentanyl BW-373U86 Carfentanil Casokefamide Cebranopadol Chloroxymorphamine Codeine DADLE DAMGO (DAGO) Dermorphin Desmetramadol (desmethyltramadol) Desomorphine Dextromoramide Dextropropoxyphene (propoxyphene) Dezocine Dimenoxadol Dimethylaminopivalophenone Eluxadoline Diamorphine (heroin) Dihydrocodeine Dihydroetorphine Dihydromorphine Diphenoxylate Dipipanone Dynorphin A Embutramide Endomorphin-1 Endomorphin-2 Eseroline Ethylmorphine Etorphine Fentanyl Fluorophen Frakefamide Furanylfentanyl Hemorphin-4 Herkinorin Hodgkinsine Hydrocodone Hydromorphinol Hydromorphone IBNtxA Ketamine Ketobemidone Kratom Laudanosine Lefetamine Leu-enkephalin Levacetylmethadol Levomethorphan Levorphanol Lexanopadol Loperamide Loxicodegol Matrine Meptazinol Met-enkephalin (metenkefalin) Methadone Metkefamide Metopon Mitragynine Mitragynine pseudoindoxyl Morphiceptin Morphine Nalbuphine Nalbuphine sebacate NalBzOH Nalmexone Naltalimide Neopine NFEPP Nicocodeine Nicodicodeine Nicomorphine NKTR-181 Norketamine Octreotide Oliceridine OM-3-MNZ Oripavine Oxycodone Oxymorphazone Oxymorphonazine Oxymorphone Oxymorphone phenylhydrazone OxyPNPH Papaver somniferum (opium) Pentazocine Pericine Pethidine (meperidine) Phenazocine Phencyclidine Piminodine Piritramide PL-017 Prodine Propiram PZM21 Racemethorphan Racemorphan Remifentanil Salsolinol SC-17599 Sinomenine Sufentanil Tapentadol Tetrahydropapaveroline TH-030418 Thebaine Thienorphine Tianeptine Tilidine Tramadol Trimebutine TRIMU 5 TRV734 Tubotaiwine U-47700 Valorphin Viminol Xorphanol PAMs: BMS-986121 BMS-986122 Antagonists: (3S,4S)-Picenadol 2-(S)-N,N-(R)-Viminol 3CS-nalmefene 4-Caffeoyl-1,5-quinide 4′-Hydroxyflavanone 4',7-Dihydroxyflavone 6β-Naltrexol 6β-Naltrexol-d4 18-MC α-Gliadin β-Chlornaltrexamine β-Funaltrexamine Akuammine Alvimopan AM-251 Apigenin AT-076 Axelopran Bevenopran Catechin Catechin gallate Clocinnamox CTAP CTOP Cyclofoxy Cyprodime Diacetylnalorphine Diprenorphine ECG EGC Epicatechin Eptazocine Gemazocine Ginsenoside R Hyperoside Ibogaine Levallorphan Lobeline LY-255582 LY-2196044 Methocinnamox Methylnaltrexone Methylsamidorphan chloride Naldemedine Nalmefene Nalodeine (N-allylnorcodeine) Nalorphine Nalorphine dinicotinate Naloxazone Naloxegol Naloxol Naloxonazine Naloxone Naltrexazone Naltrexonazine Naltrexone Naltrindole Naringenin Noribogaine Oxilorphan Pawhuskin A Rimonabant Quadazocine Samidorphan Taxifolin Unknown/unsorted: Cannabidiol Coronaridine Cyproterone acetate Dihydroakuuamine Tabernanthine Tetrahydrocannabinol
DOR	Agonists: 3CS-nalmefene 6'-GNTI 7-SIOM ADL-5747 (PF-04856881) ADL-5859 Alazocine (SKF-10047) Amoxapine AR-M100390 (ARM390) AZD2327 β-Endorphin BAM-18P Biphalin BU-48 Butorphan Butorphanol BW-373U86 Casokefamide Cebranopadol Codeine Cyclazocine DADLE Deltorphin A Deltorphin I Deltorphin II Desmethylclozapine Desmetramadol (desmethyltramadol) Dezocine Diamorphine (heroin) Dihydroetorphine Dihydromorphine DPDPE DPI-221 DPI-3290 DSLET Ethylketazocine Etorphine Fentanyl FIT Fluorophen Hemorphin-4 Hydrocodone Hydromorphone Ibogaine Isomethadone JNJ-20788560 KNT-127 Kratom Laudanosine Leu-enkephalin Levomethorphan Levorphanol Lexanopadol Lofentanil Met-enkephalin (metenkefalin) Metazocine Metkefamide Mitragynine Mitragynine pseudoindoxyl Morphine N-Phenethyl-14-ethoxymetopon Norbuprenorphine NalBzOH Oripavine Oxycodone Oxymorphone Pethidine (meperidine) Proglumide Racemethorphan Racemorphan RWJ-394674 Samidorphan SB-235863 SNC-80 SNC-162 TAN-67 (SB-205,607) TH-030418 Thebaine Thiobromadol (C-8813) Tonazocine Tramadol TRV250 Xorphanol Zenazocine Antagonists: 4',7-Dihydroxyflavone 5'-NTII 6β-Naltrexol 6β-Naltrexol-d4 α-Santolol β-Chlornaltrexamine Apigenin AT-076 Axelopran Bevenopran BNTX Catechin Catechin gallate Clocinnamox Diacetylnalorphine Diprenorphine ECG EGC Eluxadoline Epicatechin ICI-154129 ICI-174864 LY-255582 LY-2196044 Methylnaltrexone Methylnaltrindole N-Benzylnaltrindole Nalmefene Nalorphine Naltrexone Naltriben Naltrindole Naloxone Naringenin Noribogaine Pawhuskin A Quadazocine SDM25N SoRI-9409 Taxifolin Thienorphine Unknown/unsorted: 18-MC Cannabidiol Coronaridine Cyproterone acetate Tabernanthine Tetrahydrocannabinol
KOR	Agonists: 3CS-nalmefene 6'-GNTI 8-CAC 18-MC 14-Methoxymetopon β-Chlornaltrexamine β-Funaltrexamine Adrenorphin (metorphamide) Akuuamicine Alazocine (SKF-10047) Allomatrine Apadoline Asimadoline BAM-12P BAM-18P BAM-22P Big dynorphin Bremazocine BRL-52537 Butorphan Butorphanol BW-373U86 Cebranopadol Ciprefadol CR665 Cyclazocine Cyclorphan Cyprenorphine Desmetramadol (desmethyltramadol) Diamorphine (heroin) Diacetylnalorphine Difelikefalin Dihydroetorphine Dihydromorphine Diprenorphine Dynorphin A Dynorphin B (rimorphin) Eluxadoline Enadoline Eptazocine Erinacine E Ethylketazocine Etorphine Fedotozine Fentanyl Gemazocine GR-89696 GR-103545 Hemorphin-4 Herkinorin HS665 Hydromorphone HZ-2 Ibogaine ICI-199,441 ICI-204,448 Ketamine Ketazocine Laudanosine Leumorphin (dynorphin B-29) Levallorphan Levomethorphan Levorphanol Lexanopadol Lofentanil LPK-26 Lufuradom Matrine MB-1C-OH Menthol Metazocine Metkefamide Mianserin Mirtazapine Morphine Moxazocine MR-2034 N-MPPP Nalbuphine Nalbuphine sebacate NalBzOH Nalfurafine Nalmefene Nalodeine (N-allylnorcodeine) Nalorphine Naltriben Niravoline Norbuprenorphine Norbuprenorphine-3-glucuronide Noribogaine Norketamine Oripavine Oxilorphan Oxycodone Pentazocine Pethidine (meperidine) Phenazocine Proxorphan Racemethorphan Racemorphan RB-64 Salvinorin A (salvia) Salvinorin B ethoxymethyl ether Salvinorin B methoxymethyl ether Samidorphan Spiradoline (U-62,066) TH-030418 Thienorphine Tifluadom Tricyclic antidepressants (e.g., amitriptyline, desipramine, imipramine, nortriptyline) U-50,488 U-54,494A U-69,593 Xorphanol Antagonists: 4′-Hydroxyflavanone 4',7-Dihydroxyflavone 5'-GNTI 6'-GNTI 6β-Naltrexol 6β-Naltrexol-d4 β-Chlornaltrexamine Buprenorphine/samidorphan Amentoflavone ANTI Apigenin Arodyne AT-076 Axelopran AZ-MTAB Binaltorphimine BU09059 Buprenorphine Catechin Catechin gallate CERC-501 (LY-2456302) Clocinnamox Cyclofoxy Dezocine DIPPA EGC ECG Epicatechin Hyperoside JDTic LY-255582 LY-2196044 LY-2444296 LY-2459989 LY-2795050 MeJDTic Methylnaltrexone ML190 ML350 MR-2266 N-Fluoropropyl-JDTic Naloxone Naltrexone Naltrindole Naringenin Norbinaltorphimine Noribogaine Pawhuskin A PF-4455242 RB-64 Quadazocine Taxifolin UPHIT Zyklophin Unknown/unsorted: Akuammicine Akuammine Coronaridine Cyproterone acetate Dihydroakuuamine Ibogamine Tabernanthine
NOP	Agonists: (Arg14,Lys15)Nociceptin ((pF)Phe⁴)Nociceptin(1-13)NH₂ (Phe¹Ψ(CH₂-NH)Gly²)Nociceptin(1-13)NH₂ Ac-RYYRWK-NH₂ Ac-RYYRIK-NH₂ BU08070 Buprenorphine Cebranopadol Dihydroetorphine Etorphine JNJ-19385899 Levomethorphan Levorphanol Levorphanol Lexanopadol MCOPPB MT-7716 NNC 63-0532 Nociceptin (orphanin FQ) Nociceptin (1-11) Nociceptin (1-13)NH₂ Norbuprenorphine Racemethorphan Racemorphan Ro64-6198 Ro65-6570 SCH-221510 SCH-486757 SR-8993 SR-16435 TH-030418 Antagonists: (Nphe¹)Nociceptin(1-13)NH₂ AT-076 BAN-ORL-24 J-113397 JTC-801 LY-2940094 NalBzOH Nociceptin (1-7) Nocistatin SB-612111 SR-16430 Thienorphine Trap-101 UFP-101
Unsorted	β-Casomorphins Amidorphin BAM-20P Cytochrophin-4 Deprolorphin Gliadorphin (gluteomorphin) Gluten exorphins Hemorphins Kava constituents MEAGL MEAP NEM Neoendorphins Nepetalactone (catnip) Peptide B Peptide E Peptide F Peptide I Rubiscolins Soymorphins
Others	Enkephalinase inhibitors: Amastatin BL-2401 Candoxatril D -Phenylalanine Dexecadotril (retorphan) Ecadotril (sinorphan) Kelatorphan Racecadotril (acetorphan) RB-101 RB-120 RB-3007 Opiorphan Selank Semax Spinorphin Thiorphan Tynorphin Ubenimex (bestatin) Propeptides: β-Lipotropin (proendorphin) Prodynorphin Proenkephalin Pronociceptin Proopiomelanocortin (POMC) Others: Kyotorphin (met-enkephalin releaser/degradation stabilizer)
See also: Receptor/signaling modulators • Signaling peptide/protein receptor modulators

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opioid peptide