Papaver somniferum

Papaver somniferum

Papaver somniferum
Scientific classification
Kingdom:	Plantae
(unranked):	Angiosperms
(unranked):	Eudicots
Order:	Ranunculales
Family:	Papaveraceae
Genus:	Papaver
Species:	P. somniferum
Binomial name
*Papaver somniferum* L.^[1]

Papaver somniferum, the opium poppy,^[2] is the species of plant from which opium and poppy seeds are derived. Opium is the source of many drugs, including morphine (and its derivative heroin), thebaine, codeine, papaverine, and noscapine. The Latin botanical name means the "sleep-bringing poppy", referring to the sedative properties of some of these opiates.

The opium poppy is the only species of Papaveraceae that is an agricultural crop grown on a large scale. Other species, Papaver rhoeas and Papaver argemone, are important agricultural weeds, and may be mistaken for the crop.

It is also valuable for ornamental purposes, and has been known as the "common garden poppy", referencing all the group of poppy plants. Poppy seeds of Papaver somniferum are an important food item and the source of poppyseed oil, a healthy edible oil that has many uses.

Description

Papaver somniferum flower

Papaver somniferum plant showing the typical glaucous appearance

Papaver somniferum is an annual herb growing to 100 cm. All parts of the plant are strongly glaucous, giving a greyish-green appearance, and the stem and leaves are sparsely covered with coarse hairs. The leaves are lobed and clasp the stem at the base. The flowers are up to 120mm diameter, normally with four white, mauve or red petals, sometimes with dark markings at the base. The fruit is a hairless, rounded capsule topped with 12–18 radiating stigmatic rays. All parts of the plant exude white latex when wounded.^[3]^:87^[4]^:32

Varieties and cultivars

Papaver somniferum has many subspecies or varieties and cultivars. Colors of the flower vary widely, as do other physical characteristics, such as number and shape of petals, number of flowers and fruits, number of seeds, color of seeds, production of opium, etc.

Papaver somniferum Paeoniflorum Group (sometimes called Papaver paeoniflorum) is a subtype of opium poppy whose flowers are highly double, and are grown in many colors. P. somniferum Laciniatum Group (sometimes called Papaver laciniatum) is a subtype of opium poppy whose flowers are highly double and deeply lobed, to the point of looking like a ruffly pom-pom.

A few of the varieties and cultivars, notably the cultivars 'Norman' and 'Przemko',^[5] have low morphine content (less than 1%), and much higher concentrations of other alkaloids. Most varieties, however, including those most popular for ornamental use or seed production, have a higher morphine content, with the average content being 10%.^[6]^[7]

Opiates

Dried poppy seed pods and stems (plate), and seeds (bowl)

Capsule of Papaver somniferum showing latex (opium) exuding from incision

The opium poppy is, by definition, the root source of all opioids considered opiates. Morphine is the predominant alkaloid found in the varieties of opium poppy plant cultivated in most producing countries.^[8]

The seed pod of the opium poppy is the principal source of most naturally occurring μ-opioid receptor agonist opioids. Incisions are made on the green seed pods, the latex which oozes from the incisions is collected, and dried to produce "raw opium". Opium is about 8–14% morphine by dry weight, although specially bred cultivars reach 26%.^[9]

Poppy straw is the dried mature plant except the seeds, harvested by mowing.

Opiates such as morphine, thebaine, codeine, and oripavine are extracted from both the opium and the straw.

The seeds themselves contain very small amounts of opiates,^[6] and have no measurable narcotic effect in small quantities. However, the television show MythBusters demonstrated that one could test positive for narcotics after consuming four poppy seed bagels. On the show Brainiac: Science Abuse, subjects tested positive after eating only two poppy seed bagels. In addition, larger amounts of seeds may be brewed into a tea, the consumption of which has in some cases led to death by overdose. The risk stems largely from the unpredictable opiate content of the finished tea, although the interaction with other drugs can be a contributing factor.^[10]

History

Use of the opium poppy predates written history. Images of opium poppies have been found in ancient Sumerian artifacts (circa 4000 BC). The making and use of opium was known to the ancient Minoans.^[11] Its sap was later named opion by the ancient Greeks, from whence it gained its modern name of opium.

Opium was used for treating asthma, stomach illnesses, and bad eyesight.

The First and Second Opium Wars among China, the British Empire and France took place in the late 1830s through the early 1860s, when the Chinese attempted to stop western traders from selling and later smuggling opium into their country from the large crops grown in India. The British in particular had a deep trade deficit with China, and the sale of British-owned Indian opium helped balance it.

Many modern writers, particularly in the 19th century, have written on the opium poppy and its effects, notably Thomas de Quincey in Confessions of an English Opium Eater.

The French Romantic composer Hector Berlioz used opium for inspiration, subsequently producing his Symphonie Fantastique. In this work, a young artist overdoses on opium and experiences a series of visions of his unrequited love.

Opium poppies (flower and fruit) appear on the coat of arms of the Royal College of Anaesthetists.

Legality

Opium poppy fields near Metheringham, Lincolnshire, England

Opium poppies (Papaver somniferum) under cultivation in Tasmania

The United Kingdom does not require a licence for Opium poppy cultivation, but does for extracting opium for medicinal products.^[12]
Canada forbids possessing, seeking or obtaining "Opium Poppy (Papaver somniferum), its preparations, derivatives, alkaloids and salts" although an exception is made for poppy seeds.^[13]
Italy forbids cultivation of P. somniferum to extract the alkaloids, but small numbers of specimens can be grown without special permits for purely ornamental purposes.
In Austria and Switzerland, cultivation of the opium poppy is legal
In Australia P. somniferum is illegal to cultivate. 100 plants is required for determing a court of trial and 25 plants is considered intent to sell and supply.^[14]
In Germany cultivation of the opium poppy is illegal. West Germany made cultivation illegal after World War II, while East Germany did not. Only after German reunification, in 1990, did it become illegal in the east.
United Arab Emirates cultivation of the opium poppy is illegal, as is possession of poppy seeds. At least one man has been imprisoned for possessing poppy seeds obtained from a bread roll.^[15]
In New Zealand it is legal to cultivate opium poppy as long as it is not used to produce banned drugs.^[16]
Burma bans cultivation in certain provinces. In northern Burma bans have ended a century-old tradition of growing opium poppy. Between 20,000 and 30,000 ex-poppyfarmers left the Kokang region as a result of the ban in 2002.^[17] People from the Wa region, where the ban was implemented in 2005, fled to areas where growing opium is still possible.
In the United States cultivation is illegal. Opium is listed as a Schedule II controlled substance by the Drug Enforcement Administration. In addition, "Opium poppy and poppy straw" are also prohibited.^[18] However, this is not typically enforced for poppies grown or sold for ornamental or food purposes.^[6] Though the opium poppy is legal for culinary or esthetic reasons, poppies were once grown as a cash crop by farmers in California. The law of poppy cultivation in the United States is somewhat ambiguous.^[19] The reason for the ambiguity is because The Opium Poppy Control Act of 1942 (now repealed),^[20]^[21]^[22] stated that any opium poppy should be declared illegal, even if the farmers were issued a state permit.^[23] § 3 of The Opium Poppy Control Act stated:
It shall be unlawful for any person who is not the holder of a license authorizing him to produce the opium poppy, duly issued to him by the Secretary of the Treasury in accordance with the provisions of this Act, to produce the opium poppy, or to permit the production of the opium poppy in or upon any place owned, occupied, used, or controlled by him.
This led to the Poppy Rebellion, and to the Narcotics Bureau arresting anyone planting opium poppies and forcing the destruction of poppy fields of anyone who defied the prohibition of poppy cultivation.^[24]^[25] Though the press of those days favored the Federal Bureau of Narcotics, the state of California supported the farmers who grew opium poppies for their seeds for uses in foods such as poppyseed muffins. Today, this area of law has remained vague and remains somewhat controversial in the United States.^[26] The Opium Poppy Control Act of 1942 was repealed on 27 October 1970.^[27]^[28]

Medicine

Australia (Tasmania), Turkey and India are the major producers of poppy for medicinal purposes and poppy-based drugs, such as morphine or codeine.^[29] The USA has a policy of sourcing 80% of its narcotic raw materials from the traditional producers, India and Turkey.^[30]

A recent initiative to extend opium production for medicinal purposes called Poppy for Medicine was launched by The Senlis Council which proposes that Afghanistan could produce medicinal opium under a scheme similar to that operating in Turkey and India.^[31] The Council proposes licensing poppy production in Afghanistan, within an integrated control system supported by the Afghan government and its international allies, to promote economic growth in the country, create vital drugs and combat poverty and the diversion of illegal opium to drug traffickers and terrorist elements. Senlis is on record advocating reintroduction of poppy into areas of Afghanistan, specifically Kunduz, which has been poppy free for some time.

The Senlis proposal is based in part on the assertion that there is an acute global shortage of opium poppy-based medicines some of which (morphine) are on the World Health Organisation's list of essential drugs as they are the most effective way of relieving severe pain. This assertion is contradicted by the International Narcotics Control Board (INCB), the "independent and quasi-judicial control organ monitoring the implementation of the United Nations drug control conventions". INCB reports that the supply of opiates is greatly in excess of demand.^[32]

In March 2010, researchers from the Department of Biological Sciences at the University of Calgary published an article in Nature Chemical Biology about their discovery of two enzymes and their encoding genes, thebaine 6-O-demethylase (T6ODM) and codeine O-demethylase (CODM), involved in morphine biosynthesis derived from the opium poppy.^[33] The enzymes were identified as non-heme dioxygenases, and were isolated using functional genomics.^[33] Codeine O-demethylase produces the enzyme that converts codeine into morphine.^[34]

Medical cultivation in the UK

In late 2006, the British government permitted the pharmaceutical company Macfarlan Smith (a Johnson Matthey company, FTSE 100) to cultivate opium poppies in England for medicinal reasons^[35] after Macfarlan Smith's primary source, India, decided to increase the price of export opium latex. This move is well received by British farmers, with a major opium poppy field based in Didcot, England. As of 2012, they were growing in Dorset, Hampshire, Oxfordshire and Lincolnshire as a spring-sown breakcrop recognised under the single payment scheme farm subsidy.^[36] The Office of Fair Trading has alerted the government to their monopoly position on growing in the UK and worldwide production of diamorphine and recommended consideration.^[35] The government's response advocated the status quo, being concerned interference might cause the company to stop production.^[37]

Use as food

Polish makowiec, a nut roll filled with poppy seed paste

The opium poppy is the source of two food ingredients: poppy seed and poppyseed oil. The seeds contain very low levels of opiates,^[6] and the oil extracted from them contains even less. Both the oil and the seed residue also have commercial uses.

Poppy seeds

Main article: Poppy seed

Poppy seeds are commonly used in cuisine from many different cultures. They can be dry roasted and ground to be used in wet curry (curry paste) or dry curry. They have a creamy and nut-like flavor, and when used with ground coconut, the seeds provide a unique and flavour-rich curry base.^[38]

Ornamental cultivation

A red opium poppy flower used for ornamental purposes

Once known as the "common garden poppy", live plants and seeds of the opium poppy are widely sold by seed companies and nurseries in most of the western world, including the United States. Poppies are sought after by gardeners for the vivid coloration of the blooms, the hardiness and reliability of the poppy plants, the exotic chocolate-vegetal fragrance note of some cultivars, and the ease of growing the plants from purchased flats of seedlings or by direct sowing of the seed. Poppy seed pods are also sold for dried flower arrangements.

Since "opium poppy and poppy straw" are listed in Schedule II of the United States' Controlled Substances Act, a DEA license may be required to grow poppies in ornamental or display gardens. In fact, the legal status of strictly ornamental poppy gardens is more nuanced, and destruction of ornamental poppy installations or prosecution of gardeners (except those caught extracting opium via capsule scarification or tea extraction) are virtually unheard of.^[6] During the early spring, opium poppies can be seen flowering in gardens throughout North America and Europe, and beautiful displays are found in many private planters, as well as in public botanical and museum gardens (e.g., United States Botanical Garden, Missouri Botanical Garden, North Carolina Botanical Garden).

Many countries grow the plants, and some rely heavily on the commercial production of the drug as a major source of income. As an additional source of profit, the seeds of the same plants are sold for use in foods, so the cultivation of the plant is a significant source of income. This international trade in seeds of P. somniferum was addressed by a UN resolution "to fight the international trade in illicit opium poppy seeds" on 28 July 1998.

In popular culture

In the 19th century Thomas de Quincey wrote Confessions of an English Opium-Eater (1821). A book on Opium and allegedly the first book in the series of drug-addiction literature.

Recently, a feature film entitled The Opium Eater was released exploring the life of Eric Detzer and how he would go about acquiring opium poppies from flower shops and gardens in the Pacific Northwest (north of Seattle) to feed his addiction. This true story is based on an autobiography, Poppies: Odyssey of an Opium Eater written by Detzer, and starring David Bertelsen. Since the festival release of this film in Breckenridge, CO, eBay has stopped allowing the sale of opium poppy pods on their auction site. This may also be attributed to the death of a Colorado teen, who overdosed on opium tea around the same time.

What may be the most well known literary use of the poppy occurs both in L. Frank Baum's The Wonderful Wizard of Oz and in MGM's classic 1939 film based on the novel.

In the novel, while on their way to the Emerald City, Dorothy, the Scarecrow, the Tin Man, and the Cowardly Lion walk through a field of poppies, and both Dorothy and the Lion mysteriously fall asleep. The Scarecrow and the Tin Man, not being made of flesh and blood, are unaffected. They carry Dorothy to safety and place her on the ground beyond the poppy field. While they are considering how to help the Lion, a field mouse runs in front of them, fleeing a cougar. The Tin Man beheads the cougar with his axe, and the field mouse pledges her eternal gratitude. Being the Queen of the Field Mice, she gathers all her subjects together. The Tin Man cuts down several trees, and builds a wagon. The Lion is pushed onto it, and the mice pull the wagon safely out of the poppy field.

In the 1939 film, the sequence is considerably altered. The poppy field is conjured up by the Wicked Witch of the West, and it appears directly in front of the Emerald City, preventing the four travelers from reaching it. As in the novel, Dorothy and the Cowardly Lion fall asleep, but in a direct reversal of the book, the Scarecrow and the Tin Man are unable to carry Dorothy. Glinda, who has been watching over them, conjures up a snowfall which kills the poppies' narcotic power and enables Dorothy and the Lion to awaken. Unfortunately, the Tin Man has been weeping in despair, and the combination of his tears and the wet snow has caused him to rust. After he is oiled by Dorothy, the four skip happily toward the Emerald City.

In Baum's other Oz books, Oz's ruler, Princess Ozma, is often shown wearing poppies in her hair as decoration.

In George R.R. Martin's A Song Of Ice And Fire book series and its TV adaptation Game of Thrones there is a medicine called "milk of the poppy", which is made from crushed poppies and used as a painkiller and sedative. It is not specified if it is made from the opium poppy or a fictionalized version of it.

Afghanistan

Main article: Opium production in Afghanistan

After the ousting of the Taliban from the town of Marja in the southern Afghan province Helmand by Operation Moshtarak, American and NATO commanders were confronted with the dilemma of, on the one hand, the need to "win the hearts and minds" of the local population and, on the other, the need to eradicate poppy fields and destroy the opium economy that allegedly financed the Taliban insurgency. It has been speculated that US Marines were initially ordered to ignore the crops to avoid trampling the local farmers' livelihood, and that this might have been because there were no significant poppy fields there before the first US forces arrived.^[39]^[40]

References

↑ Linnaeus, Carl von (1753). Species Plantarum. Laurentius Salvius. p. 508.
↑ "BSBI List 2007". Botanical Society of Britain and Ireland. Archived from the original (xls) on 2015-02-25. Retrieved 2014-10-17.
↑ Stace, C.A. (2010). New flora of the British isles (Third ed.). Cambridge, U.K.: Cambridge University Press. ISBN 9780521707725.
↑ Blamey, M.; Fitter, R.; Fitter, A (2003). Wild flowers of Britain and Ireland: The Complete Guide to the British and Irish Flora. London: A & C Black. ISBN 978-1408179505.
↑ US 6067749 - Papaver somniferum strain with high concentration of thebaine and oripavine
1 2 3 4 5 "Poppy law" on Erowid.org
↑ Ayatollah (2006-02-25). "How potent are the major culinary (spicerack) varieties such as McCormick?". Poppies. Retrieved 2009-09-02.
↑ "International Narcotics Control Bureau, Technical Reports, 2008, Part IV, Statistical information on narcotic drugs" (PDF). Retrieved 30 December 2011.
↑ Kapoor L (1995). Opium Poppy: Botany, Chemistry, and Pharmacology. United States: CRC Press. p. 164. ISBN 1-56024-923-4.
↑ http://www.poppyseedtea.com/
↑ Askitopoulou, Helen; Ramoutsaki, Ioanna A; Konsolaki, Eleni. "Archaeological evidence on the use of opium in the Minoan world". International Congress Series (ScienceDirect) 1242: 23–29. doi:10.1016/S0531-5131(02)00769-0. |access-date= requires |url= (help)
↑ Phillip, Rhodri, & Barry Wigmore (2007-07-14). "The painkilling fields: England's opium poppies that tackle the NHS morphine crisis". Evening Standard. Retrieved 2009-09-02.
↑ Controlled Drugs and Substances Act 1996 http://laws-lois.justice.gc.ca/eng/acts/c-38.8/
↑ Misuse of Drugs Act 1981 (2015) http://www.slp.wa.gov.au/pco/prod/FileStore.nsf/Documents/MRDocument:28280P/$FILE/Misuse%20Of%20Drugs%20Act%201981%20-%20%5B06-e0-00%5D.pdf?OpenElement
↑ McGrath, Ginny (2008-02-08). "Travellers who 'smuggle' poppy seeds face Dubai jail". The Times (UK). Retrieved 2009-09-02.
↑ Section 9(4) of the Misuse of Drugs Act states, "It shall be a defense to a charge under subsection (1) [Cultivation of prohibited plants] if the person charged proves that the prohibited plant to which the charge relates was of the species Papaver somniferum, and that it was not intended to be a source of any controlled drug or that it was not being developed as a strain from which a controlled drug could be produced.""New Zealand Legislation: Misuse of Drugs Act 1975". Retrieved 7 July 2012.
↑ page 4 of the Drug Policy Briefing nr. 29 by the Transnational Institute
↑ Ayatollah. "Drug Scheduling". Drug Enforcement Administration. Retrieved 2009-09-02.
↑ "Bulletin on Narcotics – 1950 Issue 3 – 002". UNODC. Retrieved 30 December 2011.
↑ http://uscode.house.gov/download/pls/21C6.txt
↑ "Controlled Substances Import and Export Act". Fda.gov. Retrieved 30 December 2011.
↑ "21 U.S.C. § 188 : US Code – Section 188 TO 188N: Repealed. Pub. L. 91-513, title III, Sec. 1101(a)(7), Oct. 27, 1970, 84 Stat. 1292". Codes.lp.findlaw.com. Retrieved 30 December 2011.
↑ "Poppy Flowers". Backyardnature.net. Retrieved 30 December 2011.
↑ http://www.wcl.american.edu/journal/lawrev/08/anslinger.pdf?rd=1
↑ Association, American Bar (September 1952). "ABA Journal".
↑ "Poppin’ Up Poppies". Texasgardener.com. Retrieved 30 December 2011.
↑ "United States Code: Title 21,188 to 188n. Repealed. Pub. L. 91–513, title III, 1101(a)(7), Oct. 27, 1970, 84 Stat. 1292 | LII / Legal Information Institute". Law.cornell.edu. Retrieved 30 December 2011.
↑ "21 USC CHAPTER 6 – NARCOTIC DRUGS 01/03/2007". Joffelaw.com. Retrieved 30 December 2011.
↑ Dicker, Jason. "The Poppy Industry in Tasmania". University of Tasmania. Retrieved 2009-09-02.
↑ Braund, Claire (2001). "Research driving the Tasmanian poppy industry". Australian Society of Agronomy. Archived from the original on 29 July 2009. Retrieved 2009-09-02.
↑ "Poppy for Medicine". Poppy for Medicine. Retrieved 2009-09-02.
↑ International Narcotics Control Board, 2004, Report 2004, Vienna: International Narcotics Control Board: 23.
1 2 Jillian M Hagel and Peter J Facchini (2010-03-14). "Dioxygenases catalyze the O-demethylation steps of morphine biosynthesis in opium poppy". Nature Chemical Biology (Nature Publishing Group) 6 (4): 273–5. doi:10.1038/nchembio.317. PMID 20228795. Retrieved 2010-03-15.
↑ "Genetic secrets of poppies' painkillers unlocked". The Canadian Press, Toronto Star. 2010-03-15. Retrieved 2010-03-15.
1 2 "Review of undertakings by Macfarlan Smith Limited". Department for Business, Innovation and Skills. March 2006. Retrieved 2009-09-02.
↑ "Poppy Growing". MacFarlane Smith. October 2012. Retrieved 2012-10-03.
↑ "Opium derivatives - Government response to OFT review of undertakings by Macfarlan Smith Limited (MSL)" (PDF). Department for Business, Innovation and Skills. March 2006. Retrieved 2012-10-03.
↑ "Mahanandi » Gasagasalu ~ Bendakaaya". Nandyala.org. Retrieved 30 December 2011.
↑ Nordland, Rod (20 March 2010). "U.S. Turns a Blind Eye to Opium in Afghan Town". The New York Times. Afghanistan;Marja (Afghanistan). Retrieved 30 December 2011.
↑ "Afghan drug cartels squeeze poppy farmers". Bangkokpost.com. 21 March 2010. Retrieved 30 December 2011.

Bibliography

The Heroin Harvest
Comprehensive profile for Papaver somniferum from MaltaWildPlants.com
Opium FAQ v1.0 from Opioids.com
Opium Poppy Cultivation and Heroin Processing in Southeast Asia from the School of Pacific and Asian Studies
"Downward Spiral – Banning Opium in Afghanistan and Burma", Transnational Institute TNI, Debate Paper, June 2005
"Withdrawal Symptoms in the Golden Triangle – A Drugs Market in Disarray" TNI Paper by Tom Kramer et al.
Chouvy P.A., 2009, "Opium. Uncovering the Politics of the Poppy", London, I.B. Tauris (Cambridge, Harvard University Press: 2010)
Rätsch,Christian "The Encyclopedia of Psychoactive Plants, Enthnopharmacology and Its Applications" 1998/2005, Rochester, Vermont, Park Street Press, ISBN 978-0-89281-978-2

External links

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Opioidergics

Receptor
(ligands)

MOR	Agonists (abridged; see here for a full list): 7-Acetoxymitragynine 7-Hydroxymitragynine ψ-Akuammigine α-Chlornaltrexamine α-Narcotine Acetyldihydrocodeine Acetylfentanyl Adrenorphin (metorphamide) AH-7921 Akuammicine Akuammidine Alfentanil Anileridine Apparicine β-Endorphin BAM-12P BAM-18P BAM-22P Benzhydrocodone Benzylmorphine Bezitramide Biphalin BU08070 Buprenorphine Butorphanol Butyrfentanyl BW-373U86 Carfentanil Casokefamide Cebranopadol Chloroxymorphamine Codeine DADLE DAMGO (DAGO) Dermorphin Desomorphine Dextromoramide Dextropropoxyphene (propoxyphene) Dezocine Dimethylaminopivalophenone Eluxadoline Diamorphine (heroin) Dihydrocodeine Dihydroetorphine Dihydromorphine Diphenoxylate Dipipanone Dynorphin A Embutramide Endomorphin-1 Endomorphin-2 Eseroline Ethylmorphine Etorphine Fentanyl Fluorophen Frakefamide Hemorphin-4 Herkinorin Hodgkinsine Hydrocodone Hydromorphinol Hydromorphone IBNtxA Ketamine Ketobemidone Kratom Laudanosine Lefetamine Leu-enkephalin Levacetylmethadol Levorphanol Lexanopadol Loperamide Matrine Meptazinol Met-enkephalin (metenkefalin) Methadone Metkefamide Metopon Mitragynine Mitragynine pseudoindoxyl Morphiceptin Morphine Nalbuphine NalBzOH Nalmexone Naltalimide Neopine Nicocodeine Nicodicodeine Nicomorphine NKTR-181 Norketamine O-Desmethyltramadol Octreotide Oripavine Oxycodone Oxymorphazone Oxymorphonazine Oxymorphone Oxymorphone phenylhydrazone OxyPNPH Papaver somniferum (opium) Pentazocine Pericine Pethidine (meperidine) Phenazocine Phencyclidine Piminodine Piritramide PL-017 Prodine Propiram Remifentanil Salsolinol Sinomenine Sufentanil Tapentadol Tetrahydropapaveroline TH-030418 Thebaine Thienorphine Tianeptine Tilidine Tramadol Trimebutine TRIMU 5 TRV130 TRV734 Tubotaiwine U-47700 Valorphin Viminol PAMs: BMS-986121 BMS-986122 Antagonists: (3S,4S)-Picenadol 2-(S)-N,N-(R)-Viminol 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 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 Nalorphine Nalorphine dinicotinate Naloxazone Naloxegol Naloxol Naloxonazine Naloxone Naltrexazone Naltrexonazine Naltrexone Naltrindole Naringenin Noribogaine Oxilorphan Pawhuskin A Quadazocine Samidorphan Taxifolin Unknown/unsorted: Cannabidiol Coronaridine Cyproterone acetate Dihydroakuuamine Tabernanthine Tetrahydrocannabinol

DOR	Agonists: 6'-GNTI 7-SIOM ADL-5747 (PF-04856881) ADL-5859 Amoxapine AR-M100390 (ARM390) AZD2327 β-Endorphin BAM-18P Biphalin BU-48 Butorphanol BW-373U86 Casokefamide Cebranopadol Codeine Cyclazocine DADLE Deltorphin A Deltorphin I Deltorphin II Desmethylclozapine 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 Levorphanol Lexanopadol Lofentanil Met-enkephalin (metenkefalin) Metazocine Metkefamide Mitragynine Mitragynine pseudoindoxyl Morphine N-Phenethyl-14-ethoxymetopon Norbuprenorphine NalBzOH O-Desmethyltramadol Oripavine Oxycodone Oxymorphone Pethidine (meperidine) Proglumide RWJ-394674 SB-235863 SKF-10047 SNC-80 SNC-162 TAN-67 (SB-205,607) TH-030418 Thebaine Thiobromadol (C-8813) Tianeptine 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: 6'-GNTI 8-CAC 18-MC 14-Methoxymetopon β-Chlornaltrexamine β-Funaltrexamine Adrenorphin (metorphamide) Akuuamicine Alazocine Allomatrine Asimadoline BAM-12P BAM-18P BAM-22P Big dynorphin Bremazocine BRL-52537 Butorphanol BW-373U86 Cebranopadol Ciprefadol CR665 Cyclazocine Cyclorphan Cyprenorphine Diamorphine (heroin) Diacetylnalorphine Difelikefalin Dihydroetorphine Dihydromorphine 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 Levorphanol Lexanopadol Lofentanil LPK-26 Lufuradom Matrine MB-1C-OH Menthol Metazocine Metkefamide Mianserin Mirtazapine Morphine Moxazocine MR-2034 N-MPPP Nalbuphine NalBzOH Nalfurafine Nalmefene Nalorphine Naltriben Norbuprenorphine Norbuprenorphine-3-glucuronide Noribogaine Norketamine O-Desmethyltramadol Oripavine Oxilorphan Oxycodone Pentazocine Pethidine (meperidine) Phenazocine Proxorphan RB-64 Salvinorin A (salvia) Salvinorin B ethoxymethyl ether Salvinorin B methoxymethyl ether SKF-10047 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 Binaltorphimine BU09059 Buprenorphine Catechin Catechin gallate CERC-501 (LY-2456302) Clocinnamox Cyclofoxy Dezocine DIPPA Diprenorphine EGC ECG Epicatechin Hyperoside JDTic LY-255582 LY-2196044 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 Levorphanol Lexanopadol MCOPPB MT-7716 NNC 63-0532 Nociceptin (orphanin FQ) Nociceptin (1-11) Nociceptin (1-13)NH₂ Norbuprenorphine 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 / unknown	β-Casomorphins Amidorphin BAM-20P Cytochrophin-4 Deprolorphin Gliadorphin (gluteomorphin) Gluten exorphins Hemorphins Kava constituents MEAGL MEAP NEM Neoendorphins Peptide B Peptide E Peptide F Peptide I Rubiscolins Soymorphins

Enzyme
(inhibitors)

Enkephalinase	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)

Others

Propeptides: β-Lipotropin (proendorphin)
Prodynorphin
Proenkephalin
Pronociceptin
Proopiomelanocortin (POMC)

Others: Kyotorphin (met-enkephalin releaser/degradation stabilizer)

See also: Neuropeptidergics • Peptidergics

Authority control	NDL: 00565636

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