Identification

Name
Opium
Accession Number
DB11130
Type
Small Molecule
Groups
Approved, Illicit
Description

Opium is the first substance of the diverse group of the opiates. It has been known for a long time, and the first evidence of a poppy culture dates from 5 thousand years by the Sumerians. During the years, opium was used as a sedative and hypnotic, but it was determined to be addictive.[1]

Opium is extracted from Papaver somniferum, which is more known as poppies. This plant is an integrant of the Papaveraceae family, and it is characterized by solitary leaves and capsulated fruits. Therefore, opium is a sticky brown resin obtained by collecting and drying the latex that exudes from the poppy pods.[13]

Once extracted, opium contains two main groups of alkaloids; the psychoactive constituents which are in the category of phenanthrenes and alkaloids that have no central nervous system effect in the category of isoquinolines. Morphine is the most prevalent and principal alkaloid in opium, and it is responsible for most of the harmful effects of opium.[14]

Opium has gradually been superseded by a variety of synthetic opioids and general anesthetics. Some of the isolated derivatives of opium are morphine, noscapine, strychnine, veratrine, colchicine, codeine, and quinine.[2] Opium is a prohibited drug of abuse in most countries, but the illegal production of this drug and its derivatives keeps being registered. There is some legal production of opium in different countries for the obtention of alkaloids by extraction.[15]

Synonyms
  • Opio
  • Papaver somniferum exudate
  • Papaver somniferum resin
External IDs
IDS-NO-001
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Opium TeintureTincture200 gOralLaboratoire Atlas Inc1951-12-311996-09-09Canada
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Camphorated Opium TinctureOpium (5 ml) + Benzoic Acid (500 mg) + Camphor (300 mg)TinctureOralD.C. Labs Limited1951-12-312003-07-11Canada
Diban CapOpium (12 mg) + Atropine sulfate (9.7 mcg) + Attapulgite (300 mg) + Hyoscyamine sulfate (0.0519 mg) + Pectin (71.4 mg) + Scopolamine (3.3 mcg)CapsuleOralWyeth Ayerst Canada Inc.1998-02-182001-01-30Canada
Diban CapOpium (12 mg) + Atropine sulfate (9.7 mcg) + Attapulgite (300 mg) + Hyoscyamine sulfate (0.0519 mg) + Pectin (71.4 mg) + Scopolamine (3.3 mcg)CapsuleOralAyerst Laboratories1992-12-311999-04-12Canada
Donnagel-PG CapOpium (12 mg) + Attapulgite (300 mg) + Pectin (71.4 mg)CapsuleOralWyeth Ayerst Canada Inc.1994-12-312002-03-20Canada
Donnagel-PG LiqOpium (24 mg) + Kaolin (6 g) + Pectin (142.8 mg)LiquidOralWyeth Ayerst Canada Inc.1994-12-312001-04-23Canada
Opium and Belladonna SupOpium (65 mg) + Belladonna (15 mg)SuppositoryRectalSmithkline Beecham Pharma Division Of Smithkline Beecham Inc1993-12-311998-07-28Canada
Opium Camphre Tanin TabOpium (15 mg) + Camphor (60 mg) + Tannic acid (120 mg)TabletOralRougier Pharma Division Of Ratiopharm Inc1951-12-311999-09-27Canada
ParegoriqueOpium (50 ml) + Camphor (3 g)TinctureOralLaboratoire Atlas Inc1951-12-312006-06-14Canada
PMS-opium and Belladona SupOpium (65 mg) + Belladonna (15 mg)SuppositoryRectalPharmascience Inc1991-12-312016-10-28Canada
Sandoz Opium & BelladonnaOpium (65 mg) + Belladonna (15 mg)SuppositoryRectalSandoz Canada Incorporated1991-12-31Not applicableCanada
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Belladonna and OpiumOpium (60 mg/1) + Belladonna (16.2 mg/1)SuppositoryRectalPaddock Laboratories, LLC1997-04-22Not applicableUs
Belladonna and OpiumOpium (30 mg/1) + Belladonna (16.2 mg/1)SuppositoryRectalPaddock Laboratories, LLC1994-05-01Not applicableUs
Categories
UNII
37M3MZ001L
CAS number
8008-60-4
Weight
Not Available
Chemical Formula
Not Available
InChI Key
Not Available
InChI
Not Available
IUPAC Name
Not Available
SMILES
Not Available

Pharmacology

Indication

Opium and its derivatives are the most commonly used medications for the treatment of acute and chronic pain. Opium and its alkaloid-derivatives can also be used as tranquilizers, antitussives and in the treatment of diarrhea.[11] The direct use of opium is not common nowadays but the use of some of its derivatives such as morphine and codeine, as well as the use of a tincture of opium for severe diarrhea can be seen in medical practice.[12]

Illegal use of opium has been registered to be for both recreational and medicinal purposes.[3]

Pharmacodynamics

Opioids can reduce the intensity and unpleasant feeling of pain. The unspecific effect of opium to the different opioid receptors produce the generation of various effects such as sedation, euphoria, dysphoria, respiratory depression, constipation, pruritus, nausea, and vomiting. It is reported that the secondary effects tend to be diminished as long-term use tolerance is developed. Some reports have also shown an opioid-driven impairment of the hypothalamic function that can result in a loss of libido, impotence, and infertility. Patients have reported a sensation of stress relief even in presence of pain as well as the presence of sedation, hypoventilation, cough inhibition, prolonged apnea, myosis and respiratory obstruction.[9]

In the cardiovascular system, there are reports of peripheral vasodilatation, including cutaneous causing flushing of the face, neck, and thorax, impaired sympathetic reflexes and postural hypotension. In the gastrointestinal and urogenital system, the increase in smooth muscle tone has been shown to produce reduced peristalsis, delayed gastric emptying and urinary retention.[9]

Mechanism of action

Opium produces its effects by activating specific G protein-coupled receptors in the brain, spinal cord, and peripheral nervous system. There are three major classes of opioid receptors being δ-opioid, κ-opioid and μ-opioid. Opium will generate an agonist activity which will later open the potassium channels and prevent the opening of voltage-gated calcium channels. This activity causes a reduction in neuronal excitability and inhibits the release of pain neurotransmitters.[9]

The addictive character of opium is related to the binding to the μ-opioid receptors, which will activate dopaminergic neurons in the ventral tegmental area of the midbrain and thus, enhance the dopamine release in the nucleus accumbens. This mechanism involves the reward activity of the mesolimbic dopaminergic pathway.[10]

TargetActionsOrganism
ADelta-type opioid receptor
agonist
Human
AKappa-type opioid receptor
agonist
Human
AMu-type opioid receptor
agonist
Human
Absorption

After oral administration, opium bioavailability is poor.[9] In the form of opioid tincture, the Cmax and AUC of opium are between 16-24 mg/ml and 3237-6727 ng/ml.h, respectively.[4]

Volume of distribution

Opium presents a large volume of distribution that exceeds the total body water.[9]

Protein binding

The protein binding of the alkaloids that form opium, such as morphine and codeine, can range from 20-60% depending on the specific alkaloid. The highest binding proteins for opium alkaloids are albumin and beta-globulin II.[5]

Metabolism

Opium contains 50 different alkaloid opiates. The most common metabolism of opiates is to be ultimately converted to morphine which is further converted to morphine-3,6-diglucuronide.[16] Opioids are metabolized vastly by the enzyme CYP 2D6 and any mutation in this kind of enzyme or coadministration with drugs that interfere with this enzyme may generate a change in the metabolism speed.[18] For years, because of this metabolism pathway, it was very hard to differentiate between illicit heroin users and involuntary exposure to poppy seeds. The original tests for this differentiations were based in the presence of morphine in urine without evidence of 6-monoacetylmorphine. Now it is known the presence of a glucuronide metabolite only in the consumption of heroin called ATM4G and this allows a clear differentiation of the consumption of illegal heroin and poppy seed ingestion.[6]

Route of elimination

Opium is a mixture of different alkaloids including morphine and codeine. After a single ingestion of opium preparations, codeine and morphine can be found excreted in urine. The presence of codeine and morphine in urine seems to be detectable 2-12 hours and 2-36 hours post administration, respectively. The urinary excretion of morphine and codeine seems to be longer as the dose of opium is increased. After multiple dosages of opium, the presence of codeine and morphine in urine could be detected even after 48 and 84 hours post administration, respectively.[7] After ingestion of poppy seeds, it is possible to collect morphine and codeine in urine 3-25 hours and 3-22 hours after administration, respectively.[8]

Half life

The half-life of opium ranges between 3-10 hours.[9]

Clearance
Not Available
Toxicity

Some toxicity concerns from the consumption of opium are the generation of addiction, physical dependence and tolerance to the effect. Studies regarding the opioid tolerance in the treatment of chronic pain have not been systematically investigated. There are also concerns about the opioid-driven modification of endocrine function, currently reported as lower testosterone levels, loss of libido, amenorrhea and infertility.[17]

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of Opium can be decreased when combined with (R)-warfarin.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Opium.
2,5-Dimethoxy-4-ethylamphetamineThe risk or severity of serotonin syndrome can be increased when 2,5-Dimethoxy-4-ethylamphetamine is combined with Opium.
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of serotonin syndrome can be increased when Opium is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3,4-MethylenedioxyamphetamineThe risk or severity of serotonin syndrome can be increased when 3,4-Methylenedioxyamphetamine is combined with Opium.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Opium.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of serotonin syndrome can be increased when 4-Bromo-2,5-dimethoxyamphetamine is combined with Opium.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Opium.
4-MethoxyamphetamineThe risk or severity of adverse effects can be increased when 4-Methoxyamphetamine is combined with Opium.
5-androstenedioneThe metabolism of Opium can be decreased when combined with 5-androstenedione.
Food Interactions
Not Available

References

General References
  1. Duarte DF: [Opium and opioids: a brief history.]. Rev Bras Anestesiol. 2005 Feb;55(1):135-46. [PubMed:19471817]
  2. Huxtable RJ, Schwarz SK: The isolation of morphine--first principles in science and ethics. Mol Interv. 2001 Oct;1(4):189-91. [PubMed:14993340]
  3. Lee S, Park Y, Han E, Choi H, Chung H, Oh SM, Chung KH: Thebaine in hair as a marker for chronic use of illegal opium poppy substances. Forensic Sci Int. 2011 Jan 30;204(1-3):115-8. doi: 10.1016/j.forsciint.2010.05.013. Epub 2010 Jun 16. [PubMed:20558018]
  4. Somogyi AA, Larsen M, Abadi RM, Jittiwutikarn J, Ali R, White JM: Flexible dosing of tincture of opium in the management of opioid withdrawal: pharmacokinetics and pharmacodynamics. Br J Clin Pharmacol. 2008 Nov;66(5):640-7. doi: 10.1111/j.1365-2125.2008.03277.x. [PubMed:19032172]
  5. Judis J: Binding of codeine, morphine, and methadone to human serum proteins. J Pharm Sci. 1977 Jun;66(6):802-6. [PubMed:874779]
  6. Chen P, Braithwaite RA, George C, Hylands PJ, Parkin MC, Smith NW, Kicman AT: The poppy seed defense: a novel solution. Drug Test Anal. 2014 Mar;6(3):194-201. doi: 10.1002/dta.1590. Epub 2013 Dec 12. [PubMed:24339374]
  7. Liu HC, Ho HO, Liu RH, Yeh GC, Lin DL: Urinary excretion of morphine and codeine following the administration of single and multiple doses of opium preparations prescribed in Taiwan as "brown mixture". J Anal Toxicol. 2006 May;30(4):225-31. [PubMed:16803659]
  8. Struempler RE: Excretion of codeine and morphine following ingestion of poppy seeds. J Anal Toxicol. 1987 May-Jun;11(3):97-9. [PubMed:3599922]
  9. Lee M. and Abrahams M. (2012). Clinical pharmacology (11th ed.). Churchill Livingstone.
  10. Michael-Titus A., Revest P. and Shortland P. (2010). The nervous system (2nd ed.). Churchill Livingstone.
  11. Hanna M., Ouanes J. and Garcia V. (2014). Practical Management of Pain (5th ed.). Mosby.
  12. Le Coutuer P. and Burreson J. (2003). Napoleon's Buttons: 17 molecules that changed history. Tarcher.
  13. Chemical and engineering news [Link]
  14. Encyclopedia [Link]
  15. WHO [Link]
  16. NZIC [Link]
  17. FDA Reports [Link]
  18. Health partners [Link]
External Links
PubChem Substance
347911129
Wikipedia
Opium
ATC Codes
N02AA02 — OpiumA07DA02 — Opium
AHFS Codes
  • 28:08.08 — Opiate Agonists
MSDS
Download (252 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3RecruitingTreatmentOpioid Dependence1
4CompletedTreatmentCalcium Nephrolithiasis1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
TinctureOral
CapsuleOral
LiquidOral
SuppositoryRectal
TabletOral
TinctureOral200 g
Prices
Not Available
Patents
Not Available

Properties

State
Liquid
Experimental Properties
PropertyValueSource
boiling point (°C)73.3ºC (Opium 2% tincture)'MSDS'
water solubilitySoluble (Opium 2% tincture)'MSDS'
Predicted Properties
Not Available
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Taxonomy

Classification
Not classified

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
Opioid receptor activity
Specific Function
G-protein coupled receptor that functions as receptor for endogenous enkephalins and for a subset of other opioids. Ligand binding causes a conformation change that triggers signaling via guanine n...
Gene Name
OPRD1
Uniprot ID
P41143
Uniprot Name
Delta-type opioid receptor
Molecular Weight
40368.235 Da
References
  1. Lee M. and Abrahams M. (2012). Clinical pharmacology (11th ed.). Churchill Livingstone.
  2. Michael-Titus A., Revest P. and Shortland P. (2010). The nervous system (2nd ed.). Churchill Livingstone.
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
Opioid receptor activity
Specific Function
G-protein coupled opioid receptor that functions as receptor for endogenous alpha-neoendorphins and dynorphins, but has low affinity for beta-endorphins. Also functions as receptor for various synt...
Gene Name
OPRK1
Uniprot ID
P41145
Uniprot Name
Kappa-type opioid receptor
Molecular Weight
42644.665 Da
References
  1. Lee M. and Abrahams M. (2012). Clinical pharmacology (11th ed.). Churchill Livingstone.
  2. Michael-Titus A., Revest P. and Shortland P. (2010). The nervous system (2nd ed.). Churchill Livingstone.
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
Voltage-gated calcium channel activity
Specific Function
Receptor for endogenous opioids such as beta-endorphin and endomorphin. Receptor for natural and synthetic opioids including morphine, heroin, DAMGO, fentanyl, etorphine, buprenorphin and methadone...
Gene Name
OPRM1
Uniprot ID
P35372
Uniprot Name
Mu-type opioid receptor
Molecular Weight
44778.855 Da
References
  1. Lee M. and Abrahams M. (2012). Clinical pharmacology (11th ed.). Churchill Livingstone.
  2. Michael-Titus A., Revest P. and Shortland P. (2010). The nervous system (2nd ed.). Churchill Livingstone.

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Health partners [Link]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Gesell A, Rolf M, Ziegler J, Diaz Chavez ML, Huang FC, Kutchan TM: CYP719B1 is salutaridine synthase, the C-C phenol-coupling enzyme of morphine biosynthesis in opium poppy. J Biol Chem. 2009 Sep 4;284(36):24432-42. doi: 10.1074/jbc.M109.033373. Epub 2009 Jun 30. [PubMed:19567876]

Carriers

Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Binder
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. Judis J: Binding of codeine, morphine, and methadone to human serum proteins. J Pharm Sci. 1977 Jun;66(6):802-6. [PubMed:874779]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Binder
General Function
Identical protein binding
Specific Function
Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system.
Gene Name
B2M
Uniprot ID
P61769
Uniprot Name
Beta-2-microglobulin
Molecular Weight
13714.43 Da
References
  1. Judis J: Binding of codeine, morphine, and methadone to human serum proteins. J Pharm Sci. 1977 Jun;66(6):802-6. [PubMed:874779]

Drug created on December 03, 2015 09:51 / Updated on November 17, 2018 07:25