Morphine
Systematic (IUPAC) name
(5α,6α)-7,8-didehydro- 4,5-epoxy-17-methylmorphinan-3,6-diol
Identifiers
CAS number	57-27-2
ATC code	N02AA01
PubChem	5288826
DrugBank	APRD00215
Chemical data
Formula	C17H19NO3
Mol. mass	285.4
Pharmacokinetic data
Bioavailability	~25% (oral); 100% (IV);
Protein binding	30–40%
Metabolism	Hepatic 90%
Half life	2–3 hours
Excretion	Renal 90%, biliary 10%
Therapeutic considerations
Pregnancy cat.	C(AU) C(US) Morphine was an alternative rock group formed by Mark Sandman and Dana Colley in Cambridge, Massachusetts, USA, in 1989. ... Image File history File links Download high-resolution version (1100x1118, 65 KB) File links The following pages on the English Wikipedia link to this file (pages on other projects are not listed): Morphine Category: ... Image File history File links Download high-resolution version (945x1100, 234 KB) File links The following pages on the English Wikipedia link to this file (pages on other projects are not listed): Morphine ... IUPAC nomenclature is a system of naming chemical compounds and of describing the science of chemistry in general. ... Morphinan is the base chemical structures of a subgroup of opioids. ... CAS registry numbers are unique numerical identifiers for chemical compounds, polymers, biological sequences, mixtures and alloys. ... The Anatomical Therapeutic Chemical Classification System is used for the classification of drugs. ... A section of the Anatomical Therapeutic Chemical Classification System. ... PubChem is a database of chemical molecules. ... The DrugBank database available at the University of Alberta is a unique bioinformatics and cheminformatics resource that combines detailed drug (i. ... A chemical formula is an easy way of expressing information about the atoms that constitute a particular chemical compound. ... For other uses, see Carbon (disambiguation). ... This article is about the chemistry of hydrogen. ... General Name, symbol, number nitrogen, N, 7 Chemical series nonmetals Group, period, block 15, 2, p Appearance colorless gas Standard atomic weight 14. ... This article is about the chemical element and its most stable form, or dioxygen. ... The molecular mass (abbreviated Mr) of a substance, formerly also called molecular weight and abbreviated as MW, is the mass of one molecule of that substance, relative to the unified atomic mass unit u (equal to 1/12 the mass of one atom of carbon-12). ... In pharmacology, bioavailability is used to describe the fraction of an administered dose of unchanged drug that reaches the systemic circulation, one of the principal pharmacokinetic properties of drugs. ... A drugs efficacy may be affected by the degree to which it binds to the proteins within blood plasma. ... Drug metabolism is the metabolism of drugs, their biochemical modification or degradation, usually through specialized enzymatic systems. ... The liver is an organ in vertebrates including humans. ... The biological half-life of a substance is the time required for half of that substance to be removed from an organism by either a physical or a chemical process. ... The kidneys are important excretory organs in vertebrates. ... The pregnancy category of a pharmaceutical agent is an assessment of the risk of fetal injury due to the pharmaceutical, if it is used as directed by the mother during pregnancy. ... For other uses, see Australia (disambiguation). ... For other uses of terms redirecting here, see US (disambiguation), USA (disambiguation), and United States (disambiguation) Motto In God We Trust(since 1956) (From Many, One; Latin, traditional) Anthem The Star-Spangled Banner Capital Washington, D.C. Largest city New York City National language English (de facto)1 Demonym American...
Legal status	Controlled (S8)(AU) Schedule I(CA) Class A(UK) Schedule II(US) The regulation of therapeutic goods, that is drugs and therapeutic devices, varies by jurisdiction. ... The Standard for the Uniform Scheduling of Drugs and Poisons, abbreviated SUSDP, is a document used in the regulation of drugs and poisons in Australia. ... For other uses, see Australia (disambiguation). ... The Controlled Drugs and Substances Act is Canadas federal drug control statute. ... Motto (Latin for From Sea to Sea) Anthem O Canada Royal anthem: God Save the Queen Capital Ottawa Largest city Toronto Official languages English, French Government Parliamentary democracy and federal constitutional monarchy  -  Monarch Queen Elizabeth II  -  Governor General Michaëlle Jean  -  Prime Minister Stephen Harper Establishment  -  Act of Union February... The Misuse of Drugs Act 1971 is an Act of Parliament, by which the United Kingdom aims to control the possession and supply of numerous drugs and drug-like substances, as listed under the Act, and to enable international co-operation against illegal drug trafficking. ... This box:      The Controlled Substances Act (CSA) was enacted into law by the Congress of the United States as Title II of the Comprehensive Drug Abuse Prevention and Control Act of 1970. ... For other uses of terms redirecting here, see US (disambiguation), USA (disambiguation), and United States (disambiguation) Motto In God We Trust(since 1956) (From Many, One; Latin, traditional) Anthem The Star-Spangled Banner Capital Washington, D.C. Largest city New York City National language English (de facto)1 Demonym American...
Dependence Liability	Extremely high
Routes	Smoked/inhaled, insufflated, Oral, SC, IM, IV

Morphine (INN) (pronounced /ˈmɔrfiːn/) is a highly potent opiate analgesic drug and is the principal active agent in opium and the prototypical opioid. It is also a natural endocrine product in humans and other animals. Like other opioids, e.g., diacetylmorphine (heroin), morphine acts directly on the central nervous system (CNS) to relieve pain, and at synapses of the nucleus accumbens in particular. Studies done on the efficacy of various opioids have indicated that, in the management of severe pain, no other narcotic analgesic, other than Fentanyl (which has a higher potency, but is shorter acting), is more effective or superior to morphine. Morphine is highly addictive when compared to other substances; tolerance, physical and psychological dependences develop very rapidly. The word morphine is derived from Morpheus, one of the Greek gods of dreams. An International Nonproprietary Name (INN) is the official non-proprietary or generic name given to a pharmaceutical substance, as designated by the World Health Organization. ... For other uses see Opiate (disambiguation), or for the class of drugs see Opioid. ... An analgesic (colloquially known as a painkiller) is any member of the diverse group of drugs used to relieve pain (achieve analgesia). ... This article does not cite any references or sources. ... This article is about the drug. ... An opioid is a chemical substance that has a morphine-like action in the body. ... Diacetylmorphine (INN), diamorphine (BAN), or more commonly heroin, is a semi-synthetic opioid. ... Heroin (INN: diacetylmorphine, BAN: diamorphine) is a semi-synthetic opioid synthesized from morphine, a derivative of the opium poppy. ... A diagram showing the CNS: 1. ... Illustration of the major elements in a prototypical synapse. ... The nucleus accumbens (NAcc), also known as the accumbens nucleus or as the nucleus accumbens septi (Latin for nucleus leaning against the septum), is a collection of neurons located where the head of the caudate and the anterior portion of the putamen meet just lateral to the septum pellucidum. ... Fentanyl is an opioid analgesic, first synthesized by Janssen Pharmaceutica (Belgium) in the late 1950s, with a potency many times that of morphine. ... This article is about the concept of addiction. ... Drug tolerance occurs when a subjects reaction to a drug (such as a painkiller or intoxicant) decreases so that larger doses are required to achieve the same effect. ... Sleep and his half-brother Death (Hypnos and Thanatos) by John William Waterhouse (1874) Morpheus (he who forms, shapes, moulds, from the Greek morphe) is the Greek god of dreams. ... In Greek mythology, the Oneiroi were the sons of Hypnos, the god of sleep. ...

Medical uses

Morphine is used legally:

• as an analgesic in hospital settings to relieve
  • pain in myocardial infarction
  • pain in sickle cell crisis
  • pain associated with surgical conditions, pre- and postoperatively
  • pain associated with trauma
• in the relief of severe chronic pain, e.g.,
  • cancer
  • pain from kidney stones (renal colic, ureterolithiasis)
  • severe back pain
• as an adjunct to general anesthesia
• in epidural anesthesia or intrathecal analgesia
• for palliative care (i.e., to alleviate pain without curing the underlying reason for it, usually because the latter is found impossible)
• as an antitussive for severe cough
• in nebulized form, for treatment of dyspnea, although the evidence for efficacy is slim.^[1] Evidence is better for other routes.^[2]
• as an antidiarrheal in chronic conditions (e.g., for diarrhea associated with AIDS, although loperamide (a non-absorbed opioid acting only on the gut) is the most commonly used opioid for diarrhea).

Heart attack redirects here. ... ... Cancer is a class of diseases or disorders characterized by uncontrolled division of cells and the ability of these to spread, either by direct growth into adjacent tissue through invasion, or by implantation into distant sites by metastasis (where cancer cells are transported through the bloodstream or lymphatic system). ... Kidney stones are solid accretions (crystals) of dissolved minerals in urine found inside the kidneys or ureters. ... Back pain (also known dorsalgia) is pain felt in the back that may originate from the muscles, nerves, bones, joints or other structures in the spine. ... The following is about the linguistics term; adjunct is also a conjunct disjunct adverbial Categories: Linguistics stubs ... This article or section may be confusing for some readers, and should be edited to be clearer. ... The epidural space is a part of the human spine which is very close to the spinal cord, lying just outside the dura mater. ... Palliative care (from Latin palliare, to cloak) is any form of medical care or treatment that concentrates on reducing the severity of disease symptoms, rather than providing a cure. ... A cough medicine is a drug used to treat coughing and related conditions. ... Dyspnea (R06. ... An antidiarrhoeal drug is any medication which provides symptomatic relief for diarrhoea. ... For other uses, see AIDS (disambiguation). ... Imodium redirects here. ...

Contraindications

The following conditions are relative contraindications for morphine: In medicine, a contraindication is a condition or factor that increases the risk involved in using a particular drug, carrying out a medical procedure or engaging in a particular activity. ...

• acute respiratory depression
• renal failure (due to accumulation of the metabolite morphine-6-glucuronide)
• chemical toxicity (potentially lethal in low tolerance subjects)
• raised intracranial pressure, including head injury (exacerbation due pCO2 increases from respiratory depression)

Older literature, based upon studies of animals with acute pancreatitis, claimed that morphine caused significant spasm of the sphincter of Oddi and could therefore worsen the pain of the disease; however, there is no evidence to support this common misconception. This myth persists in medical practice with no basis in fact. In medicine, hypoventilation (also known as respiratory depression) occurs when ventilation is inadequate (hypo means below) to perform needed gas exchange. ... Renal failure or kidney failure is a situation in which the kidneys fail to function adequately. ... Morphine-6-glucuronide (M6G) is of more than simply academic interest, since it is the major active metabolite of morphine, and as such is the molecule responsible for much of the pain-relieving effects of morphine (and heroin and codeine). ... // Toxic and Intoxicated redirect here – toxic has other uses, which can be found at Toxicity (disambiguation); for the state of being intoxicated by alcohol see Drunkenness. ...

Further information

See Opioids An opioid is any agent that binds to opioid receptors found principally in the central nervous system and gastrointestinal tract. ...

Pharmacology

Main article: Opioid receptor

Morphine is the prototype narcotic drug and is the standard against which all other opioids are tested. It interacts predominantly with the μ-opioid receptor. These μ-binding sites are discretely distributed in the human brain, with high densities in the posterior amygdala, hypothalamus, thalamus, nucleus caudatus, putamen, and certain cortical areas. They are also found on the terminal axons of primary afferents within laminae I and II (substantia gelatinosa) of the spinal cord and in the spinal nucleus of the trigeminal nerve.^[3] To meet Wikipedias quality standards, this article may require cleanup. ... The μ opioid receptors (MOR) are a class of opioid receptors with high affinity for enkephalins and beta-endorphin but low affinity for dynorphins. ... This article is about part of the human brain. ... The hypothalamus links the nervous system to the endocrine system via the pituitary gland (hypophysis). ... The thalamus (from Greek θάλαμος = bedroom, chamber, IPA= /ˈθælÉ™mÉ™s/) is a pair and symmetric part of the brain. ... The caudate nucleus is a telencephalic nucleus, one of the input nuclei of the basal ganglia; involved with control of voluntary movement in the brain. ... The putamen is a structure in the middle of the brain, forming the striatum together with the caudate nucleus. ... Illustration of the major elements in a prototypical synapse. ... The posteromarginal nucleus, Rexed lamina I, is located at the most dorsal aspect of the dorsal horn of the spinal cord. ... The apex of the posterior column is capped by a V-shaped or crescentic mass of translucent, gelatinous neuroglia, termed the substantia gelatinosa of Rolando (or gelatinous substance of posterior horn of spinal cord), which contains both neuroglia cells, and small nerve cells. ... The trigeminal nerve is the fifth (V) cranial nerve, and carries sensory information from most of the face, as well as motor supply to the muscles of mastication (the muscles enabling chewing), tensor tympani (in the middle ear), and other muscles in the floor of the mouth, such as the...

Morphine is a phenanthrene opioid receptor agonist – its main effect is binding to and activating the μ-opioid receptors in the central nervous system. In clinical settings, morphine exerts its principal pharmacological effect on the central nervous system and gastrointestinal tract. Its primary actions of therapeutic value are analgesia and sedation. Activation of the μ-opioid receptors is associated with analgesia, sedation, euphoria, physical dependence, and respiratory depression. Morphine is a rapid-acting narcotic, and it is known to bind very strongly to the μ-opioid receptors, and for this reason, it often has a higher incidence of euphoria/dysphoria, respiratory depression, sedation, pruritus, tolerance, and physical and psychological dependence when compared to other opioids at equianalgesic doses. Morphine is also a κ-opioid and δ-opioid receptor agonist, κ-opioid's action is associated with spinal analgesia, miosis (pinpoint pupils) and psychotomimetic effects. δ-opioid is thought to play a role in analgesia.^[4] Phenanthrene is a polycyclic aromatic hydrocarbon composed of three fused benzene rings--as the above formula shows. ... To meet Wikipedias quality standards, this article may require cleanup. ... Agonists for muscle type see Agonist (muscle) An agonist is a substance that binds to a receptor and triggers a response in the cell. ... The μ opioid receptors (MOR) are a class of opioid receptors with high affinity for enkephalins and beta-endorphin but low affinity for dynorphins. ... A diagram showing the CNS: 1. ... For other uses of painkiller, see painkiller (disambiguation) An analgesic (colloquially known as painkiller) is any member of the diverse group of drugs used to relieve pain. ... The μ opioid receptors (MOR) are a class of opioid receptors with high affinity for enkephalins and beta-endorphin but low affinity for dynorphins. ... Euphoria (Greek ) is a medically recognized emotional state related to happiness. ... A chemical dependency is such a strong dependency on a substance that it becomes necessary to have this substance just to function properly; The need of a substance developed from abusing the substance, requiring the substance for survival, like the need for food, or water See also: addiction drug tolerance... In medicine, hypoventilation exists when ventilation is inadequate to perform gas exchange. ... The μ opioid receptors (MOR) are a class of opioid receptors with high affinity for enkephalins and beta-endorphin but low affinity for dynorphins. ... κ-Opioid receptors are involved with analgesia, but activation also produces marked nausea and dysphoria. ... δ-Opioid receptor activation produces analgesia. ... Miosis should not be confused with meiosis, the cellular division process involved in sexual reproduction. ... Describes the actions of a drug in producing symptoms of psychosis including delusions and/or hallucinations. ...

The effects of morphine can be countered with opioid antagonists such as naloxone and naltrexone; the development of tolerance to morphine may be inhibited by NMDA antagonists such as ketamine or dextromethorphan.^[5] Antagonists will block the binding of an agonist at a receptor molecule, inhibiting the signal produced by a receptor-agonist coupling. ... Naloxone is a drug used to counter the effects of opioid overdose, for example heroin and morphine overdose. ... Naltrexone is an opioid receptor antagonist used primarily in the management of alcohol dependence and opioid dependence. ... NMDA (N-methyl-D-aspartic acid) is an amino acid derivative acting as a specific agonist at the NMDA receptor, and therefore mimics the action of the neurotransmitter glutamate on that receptor. ... Ketamine is a dissociative anesthetic for use in human and veterinary medicine developed by Parke-Davis (1962). ... Dextromethorphan (DXM or DM) is an antitussive (cough suppressant) drug found in many over-the-counter cold and cough medicines. ...

Morphine is primarily metabolized into morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G)^[6] via glucuronidation by phase II metabolism enzyme UDP-glucuronosyl transferase-2B7 (UGT2B7). The phase I metabolism cytochrome P450 (CYP) family of enzymes has a role in the metabolism to a lesser extent. Not only does the metabolism occur in the liver but it may also take place in the brain and the kidneys. M6G has been found to be a far more potent analgesic than morphine when dosed to rodents, but crosses the blood-brain barrier with difficulty. M6G has been shown to be relatively more selective for mu-receptors than for delta- and kappa-receptors, whereas M3G does not appear to compete for opioid receptor binding. The significance of M6G formation on the observed effect of a dose of morphine is the subject of extensive debate among pharmacologists. Morphine-6-glucuronide (M6G) is of more than simply academic interest, since it is the major active metabolite of morphine, and as such is the molecule responsible for much of the pain-relieving effects of morphine (and heroin and codeine). ... Example of glucuronidation Glucuronidation of alcohols and acids Glucuronidation is a major inactivating pathway for a huge variety of exogenous and endogenous molecules, including drugs, polluants, bilirubin, androgens, estrogens, mineralocorticoids, glucocorticoids, fatty acid derivatives, retinoids and bile acids. ... UGT2B7 (UDP-Glucuronosyltransferase-2B7) is a phase II metabolism isoenzyme found to be active in the liver, kidneys, epithelial cells of the lower gastrointestinal tract and also has been reported in the brain. ... The blood-brain barrier (BBB) is a membranic structure that acts primarily to protect the brain from chemicals in the blood, while still allowing essential metabolic function. ...

Constipation

Like loperamide and other opioids, morphine acts on the myenteric plexus in the intestinal tract, reducing gut motility, causing constipation. The gastrointestinal effects of morphine are mediated primarily by μ-opioid receptors in the bowel. By inhibiting gastric emptying and reducing propulsive peristalsis of the intestine, morphine decreases the rate of intestinal transit. Reduction in gut secretion and increases in intestinal fluid absorption also contribute to the constipating effect. Opioids also may act on the gut indirectly through tonic gut spasms after inhibition of nitric oxide generation. This effect was shown in animals when a nitric oxide precursor reversed morphine-induced changes in gut motility. Imodium redirects here. ... Part of the enteric nervous system, Auerbachs plexus (or myenteric plexus) exists between the longitudinal and circular layers of muscularis externa in the gastrointestinal tract and provides motor innervation to both layers and secretomotor innervation to the mucosa. ... An opioid is a chemical substance that has a morphine-like action in the body. ...

Gene expression

Studies have shown that morphine can alter the expression of a number of genes. A single injection of morphine has been shown to alter the expression of two major groups of genes, for proteins involved in mitochondrial respiration and for cytoskeleton-related proteins.^[7] This stylistic schematic diagram shows a gene in relation to the double helix structure of DNA and to a chromosome (right). ... ... The eukaryotic cytoskeleton. ...

Effects on the immune system

Morphine has long been known to act on receptors expressed on cells of the central nervous system resulting in pain relief and analgesia. In the 1970s and '80s, evidence suggesting that opiate drug addicts show increased risk of infection (such as increased pneumonia, tuberculosis, and HIV) led scientists to believe that morphine may also affect the immune system. This possibility increased interest in the effect of chronic morphine use on the immune system. A diagram showing the CNS: 1. ... For other uses of painkiller, see painkiller (disambiguation) An analgesic (colloquially known as painkiller) is any member of the diverse group of drugs used to relieve pain. ... This article is about human pneumonia. ... Tuberculosis (abbreviated as TB for tubercle bacillus or Tuberculosis) is a common and deadly infectious disease caused by mycobacteria, mainly Mycobacterium tuberculosis. ... The human immunodeficiency virus (HIV) is a frequently mutating retrovirus that attacks the human immune system and which has been shown to cause acquired immune deficiency syndrome (AIDS). ... A scanning electron microscope image of a single neutrophil (yellow), engulfing anthrax bacteria (orange). ...

The first step of determining that morphine may affect the immune system was to establish that the opiate receptors known to be expressed on cells of the central nervous system are also expressed on cells of the immune system. One study successfully showed that dendritic cells, part of the innate immune system, display opiate receptors. Dendritic cells are responsible for producing cytokines, which are the tools for communication in the immune system. This same study showed that dendritic cells chronically treated with morphine during their differentiation produce more interleukin-12 (IL-12), a cytokine responsible for promoting the proliferation, growth, and differentiation of T-cells (another cell of the adaptive immune system) and less interleukin-10 (IL-10), a cytokine responsible for promoting a B-cell immune response (B cells produce antibodies to fight off infection).^[8] Dendritic cells (DC) are immune cells and form part of the mammal immune system. ... Cytokines are a category of less-widely-known signalling proteins and glycoproteins that, like hormones and neurotransmitters, are used extensively in cellular communication. ... Interleukin 12 (IL-12) is an interleukin that are naturally produced by macrophages and human B-lymphoblastoid cells (NC-37)in response to antigenic stimulation. ... Interleukin-10 (IL-10 or IL10), also known as human cytokine synthesis inhibitory factor (CSIF), is an anti-inflammatory cytokine, capable of inhibiting synthesis of pro-inflammatory cytokines like IFN-gamma, IL-2, IL-3, TNFα and GM-CSF by cells such as macrophages and Th1 cells. ...

This regulation of cytokines appear to occur via the p38 MAPKs (mitogen activated protein kinase) dependent pathway. Usually, the p38 within the dendritic cell expresses TLR 4 (toll-like receptor 4), which is activated through the ligand LPS (lipopolysaccharide). This causes the p38 MAPK to be phosphorylated. This phosphorylation activates the p38 MAPK to begin producing IL-10 and IL-12. When the dendritic cell is chronically exposed to morphine during their differentiation process then treated with LPS, the production of cytokines is different. Once treated with morphine, the p38 MAPK does not produce IL-10, instead favoring production of IL-12. The exact mechanism through which the production of one cytokine is increased in favor over another is not known. Most likely, the morphine causes increased phosphorylation of the p38 MAPK. Transcriptional level interactions between IL-10 and IL-12 may further increase the production of IL-12 once IL-10 is not being produced. Future research may target the exact mechanism that increases the production of IL-12 in morphine treated dendritic cells. This increased production of IL-12 causes increased T-cell immune response. This response is due to the ability of IL-12 to cause T helper cells to differentiate into the Th1 cell, causing a T cell immune response.^{[citation needed]} P38 mitogen-activated protein kinases are a class of mitogen-activated protein kinases which are responsive to stress stimuli, such as cytokines, ultraviolet irradiation, heat shock, and osmotic shock, and are involved in cell differentiation and apoptosis. ... TLR 4 is a toll-like receptor. ... Lipopolysaccharide (captions are in French) Lipopolysaccharide (LPS) is a large molecule consisting of a lipid and a polysaccharide (carbohydrate) joined by a covalent bond. ... A phosphorylated serine residue Phosphorylation is the addition of a phosphate (PO4) group to a protein molecule or a small molecule. ...

Chemistry

Most of the licit morphine produced is used to make codeine by methylation. It is also a precursor for both heroin (diacetylmorphine), hydromorphone, and oxymorphone. Replacement of the N-methyl group of morphine with an N-phenylethyl group results in a product that is 18 times more powerful than morphine in its opiate agonist potency.^{[citation needed]} Combining this modification with the replacement of the 6-hydroxyl with a 6-methylene produces a compound some 1,440 times more potent than morphine,^{[citation needed]} stronger than the Bentley compounds such as etorphine. For the band, see Codeine (band). ... Hydromorphone is a drug developed in Germany in the 1920s and introduced to the mass market beginning in 1926. ... Oxymorphone (Opana, Numorphan) or 14-Hydroxydihydromorphinone is a powerful semi-synthetic opioid analgesic that is derived from thebaine, and is approximately 6–8 times more potent than morphine. ... // Hydroxyl group The term hydroxyl group is used to describe the functional group -OH when it is a substituent in an organic compound. ... In chemistry, methylene is a divalent functional group CH2 derived formally from methane. ... Etorphine (Immobilon or M99) is a semi-synthetic opioid possessing an analgesic potency approximately 10,000 times that of morphine and was first prepared in 1960 from oripavine, which does not generally occur in opium poppy extract but rather in poppy straw and in related plants, Papaver orientale and Papaver...

Both morphine and its hydrated form, C₁₇H₁₉NO₃H₂O, are sparingly soluble in water. In five liters of water, only one gram of the hydrate will dissolve. For this reason, pharmaceutical companies produce sulfate and hydrochloride salts of the drug, both of which are over 300 times more water-soluble than their parent molecule. Whereas the pH of a saturated morphine hydrate solution is 8.5, the salts are acidic. Since they derive from a strong acid but weak base, they are both at about pH = 5; as a consequence, the morphine salts are mixed with small amounts of NaOH to make them suitable for injection.^[9] Sodium hydroxide (NaOH), also known as lye, caustic soda and (incorrectly, according to IUPAC nomenclature)[1] sodium hydrate, is a caustic metallic base. ...

It is interesting to note that morphine has recently been found to be endogenously produced by humans, made by cells in the heart, pancreas and brain.^[10] It has also been isolated from a range of other mammals, as well as toads and some invertebrates. It is unclear, however, what the normal endogenous role of morphine is.

A number of salts of morphine are used, and the opioids Morphine-N-Oxide (Genomorphine) and Pseudomorphine form as degradation products of morphine. The salts listed by the United States Drug Enforcement Administration, in addition to a few others, are as follows: The DEAs enforcement activities may take agents anywhere from distant countries to suburban U.S. homes. ...

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The Controlled Substances Act (CSA) was enacted into law by the Congress of the United States as Title II of the Comprehensive Drug Abuse Prevention and Control Act of 1970. ... The Controlled Substances Act (CSA) was enacted into law by the Congress of the United States as Title II of the Comprehensive Drug Abuse Prevention and Control Act of 1970. ... The Controlled Substances Act (CSA) was enacted into law by the Congress of the United States as Title II of the Comprehensive Drug Abuse Prevention and Control Act of 1970. ...

Production

A Hungarian chemist, Janos Kabay, found and internationally patented a method to extract morphine from "poppy straw": dried poppy pods and stem, and other parts of the dry plant, except for seeds and root. In natural form, in poppy plant, the alkaloids are bound to meconic acid. The method is to extract from the crushed plant with diluted sulfuric acid, which is a stronger acid than meconic acid, but not so strong to react with alkaloid molecules. The extraction is performed in many steps (one amount of crushed plant is at least six to ten times extracted, so practically every alkaloid goes into the solution). From the solution obtained at the last extraction step, the alkaloids are precipitated by either ammonium hydroxide or sodium carbonate. The last step is purifying and separating morphine from other opium alkaloids (opium poppy contains at least 15–20 different alkaloids, but most of them are of very low concentration). In the 1950s and 1960s, Hungary supplied nearly 60% of Europe's total legal, medication-purpose morphine production. To this day, poppy farming is legal in Hungary, but poppy farms are limited by law to 2 acres. It is also legal to sell dried poppy in flowershops for use in floral arrangements. This article is about the plant. ... In chemistry, liquid-liquid extraction is a useful method to separate components (compounds) of a mixture. ... Chemical structure of ephedrine, a phenethylamine alkaloid An alkaloid is a nitrogen-containing naturally occurring compound, produced by a large variety of organisms, including fungi, plants, animals, and bacteria. ... This article is about the drug. ...

Legal classification

• In the United Kingdom, morphine is listed as a Class A drug under the Misuse of Drugs Act 1971 and a Schedule 2 Controlled Drug under The Misuse of Drugs Regulations 2001.

• In the United States, morphine is classified as a Schedule II drug under the Controlled Substances Act.

• In Canada, morphine is classified as a Schedule I drug under the Controlled Drugs and Substances Act.

• In Australia, morphine is classified as a Schedule 8 drug under the variously titled State and Territory Poisons Acts.

• In the Netherlands, morphine is classified as a List 1 drug under the Opium Law.

• Internationally, morphine is a Schedule I drug under the Single Convention on Narcotic Drugs.^[11]

The Misuse of Drugs Act 1971 is an Act of Parliament, by which the United Kingdom aims to control the possession and supply of numerous drugs and drug-like substances, as listed under the Act, and to enable international co-operation against illegal drug trafficking. ... The Controlled Substances Act (CSA) was enacted into law by the Congress of the United States as Title II of the Comprehensive Drug Abuse Prevention and Control Act of 1970. ... This box:      The Controlled Substances Act (CSA) was enacted into law by the Congress of the United States as Title II of the Comprehensive Drug Abuse Prevention and Control Act of 1970. ... The Controlled Drugs and Substances Act is Canadas federal drug control statute. ... The Controlled Drugs and Substances Act is Canadas federal drug control statute. ... The Standard for the Uniform Scheduling of Drugs and Poisons, abbreviated SUSDP, is a document used in the regulation of drugs and poisons in Australia. ... Motto: Je Maintiendrai (Dutch: Ik zal handhaven, English: I Shall Uphold) Anthem: Wilhelmus van Nassouwe Capital Amsterdam1 Largest city Amsterdam Official language(s) Dutch2 Government Parliamentary democracy Constitutional monarchy  - Queen Beatrix  - Prime minister Jan Peter Balkenende Independence Eighty Years War   - Declared July 26, 1581   - Recognised January 30, 1648 (by Spain... Single Convention on Narcotic Drugs Opened for signature March 30, 1961 at New York Entered into force December 13, 1964[1] Conditions for entry into force 40 ratifications Parties 180[2] The Single Convention on Narcotic Drugs is the international treaty against illicit drug manufacture and trafficking that forms the...

History and non-medical use

Morphine advertisement ca. 1900^[12]

Morphine was first isolated in 1804 in Paderborn, Germany,^[13] by the German pharmacist Friedrich Wilhelm Adam Sertürner, who named it morphium after Morpheus, the Greek god of dreams. But it was not until the development of the hypodermic needle in 1853 that its use spread.^[14] It was used for pain relief, and as a "cure" for opium and alcohol addiction. Later it was found out that morphine was even more addictive than either alcohol or opium, and its extensive use during the American Civil War allegedly resulted in over 400,000^[15] sufferers from the "soldier's disease" of morphine addiction.^{[16] [17]} This idea has been a subject of controversy, as there have been suggestions that such a disease was in fact a hoax and soldier's disease did not occur after the Civil War.^[18][19] Image File history File links No higher resolution available. ... Image File history File links No higher resolution available. ... Friedrich Wilhelm Adam Sertürner (born 19 June 1783 in Neuhaus, Germany (near Paderborn), died 20 February 1841 in Hamelin) was a German pharmacist, who discovered morphine in 1803. ... Sleep and his half-brother Death (Hypnos and Thanatos) by John William Waterhouse (1874) Morpheus (he who forms, shapes, moulds, from the Greek morphe) is the Greek god of dreams. ... The bust of Zeus found at Otricoli (Sala Rotonda, Museo Pio-Clementino, Vatican) Greek mythology is the body of stories belonging to the Ancient Greeks concerning their gods and heroes, the nature of the world and the origins and significance of their own cult and ritual practices. ... Different bevels on hypodermic needles. ... Combatants United States of America (Union) Confederate States of America (Confederacy) Commanders Abraham Lincoln, Ulysses S. Grant Jefferson Davis, Robert E. Lee Strength 2,200,000 1,064,000 Casualties 110,000 killed in action, 360,000 total dead, 275,200 wounded 93,000 killed in action, 258,000 total...

Diacetylmorphine (better known as heroin) was synthesized from morphine in 1874 and brought to market by Bayer in 1898. Heroin is approximately 1.5–2 times more potent than morphine on a milligram-for-milligram basis. Using a variety of subjective and objective measures, one study estimated the relative potency of heroin to morphine administered intravenously to post-addicts to be 1.80–2.66 mg of morphine sulfate to 1 mg of diamorphine hydrochloride (heroin).^[20] The pharmacology of heroin and morphine is identical except the two acetyl groups increase the lipid solubility of the heroin molecule, causing it to cross the blood-brain barrier and enter the brain more rapidly. Once in the brain, these acetyl groups are removed to yield morphine, which causes the subjective effects of heroin. Thus, heroin may be thought of as a more rapidly acting form of morphine.^[21] Morphine was the most commonly abused narcotic analgesic in the world up until heroin was synthesized and came into use. Even today, morphine is the most sought after prescription narcotic by heroin addicts when heroin is scarce.^{[citation needed]} Diacetylmorphine (INN), diamorphine (BAN), or more commonly heroin, is a semi-synthetic opioid. ... Heroin (INN: diacetylmorphine, BAN: diamorphine) is a semi-synthetic opioid synthesized from morphine, a derivative of the opium poppy. ... Bayer AG (IPA pronunciation //) (ISIN: DE0005752000, NYSE: BAY, TYO: 4863 ) is a German chemical and pharmaceutical company founded in Barmen, Germany in 1863. ... Acetyl is the radical of acetic acid. ... ... The blood-brain barrier (BBB) is a membranic structure that acts primarily to protect the brain from chemicals in the blood, while still allowing essential metabolic function. ...

Morphine, heroin and cocaine became controlled substances in the U.S. under the Harrison Narcotics Tax Act of 1914, and possession without a prescription in the U.S. is a criminal offense. For other uses, see Cocaine (disambiguation). ... For other uses of terms redirecting here, see US (disambiguation), USA (disambiguation), and United States (disambiguation) Motto In God We Trust(since 1956) (From Many, One; Latin, traditional) Anthem The Star-Spangled Banner Capital Washington, D.C. Largest city New York City National language English (de facto)1 Demonym American... The Harrison Narcotics Tax Act was an American law that regulated and taxed the production, importation, distribution and use of opiates. ...

In 1952, Dr. Marshall D. Gates, Jr. was the first person to chemically synthesize morphine at the University of Rochester. This breakthrough is well renowned in the field of organic chemistry.^[22] The University of Rochester (UR) is a private, coeducational and nonsectarian research university located in Rochester, New York. ...

Morphine is routinely carried by soldiers on operations in an autoinjector. This article or section does not adequately cite its references or sources. ...

Slang terms for morphine include M, Big M, Miss Emma, morph, morpho, Murphy, cube, cube juice, White Nurse, Red Cross, mojo, hocus, 13, Number 13, mofo, unkie, happy powder, joy powder, first line, Aunt Emma, coby, em, emsel, morf, dope, glad stuff, goody, God's Medicine, God's Own Medicine, hard stuff, morfa, morphia, morphy, mud, sister, Sister Morphine, stuff, white stuff, white merchandise and others.

Addiction

Raw morphine (opium)

Morphine is a highly addictive substance, both psychologically and physically, with an addiction potential comparable to that of heroin. In a study comparing the physiological and subjective effects of heroin and morphine administered intravenously to a small number of post-addicts, post-addicts showed no preference for one or the other of these drugs when administered the drugs on a single injection basis, and equipotent doses of each drug had comparable effects on a number of different subjective variables. Nonetheless, most preferred heroin after multiple injections, and both heroin and morphine were strongly preferred over several other opioid analgesics (hydromorphone, fentanyl, oxycodone, and meperidine).^[20] Image File history File links Size of this preview: 800 × 521 pixelsFull resolution (3008 × 1960 pixel, file size: 3. ... Image File history File links Size of this preview: 800 × 521 pixelsFull resolution (3008 × 1960 pixel, file size: 3. ... This article is about the concept of addiction. ... Physical dependence refers to a state resulting from habitual use of a drug, where negative physical withdrawal symptoms result from abrupt discontinuation. ... Hydromorphone is a drug developed in Germany in the 1920s and introduced to the mass market beginning in 1926. ... Fentanyl is an opioid analgesic, first synthesized by Janssen Pharmaceutica (Belgium) in the late 1950s, with a potency many times that of morphine. ... Not to be confused with oxytocin. ... Pethidine (INN) or meperidine (USAN) (also referred to as: isonipecaine; lidol; operidine; pethanol; piridosal; Algil®; Alodan®; Centralgin®; Demerol®; Dispadol®; Dolantin®; Dolestine®; Dolosal®; Dolsin®; Mefedina®) is a fast-acting opioid analgesic drug. ...

Withdrawal syndrome

The withdrawal symptoms associated with morphine addiction are usually experienced shortly before the time of the next scheduled dose, sometimes within as early as a few hours (usually between 6–12 hours) after the last administration. Early symptoms include watery eyes, insomnia, diarrhea, runny nose, yawning, dysphoria, and sweating and in some cases a strong drug craving. Restlessness, irritability, loss of appetite, body aches, severe abdominal pain, nausea and vomiting, tremors, and even stronger and more intense drug craving appear as the syndrome progresses. Severe depression and vomiting are very common. The heart rate and blood pressure are elevated and can lead to a heart attack, blood clot or stroke. Chills or cold flashes with goose bumps ("cold turkey") alternating with flushing (hot flashes), kicking movements of the legs ("kicking the habit"^[23]) and excessive sweating are also characteristic symptoms.^[24] Severe pains in the bones and muscles of the back and extremities occur, as do muscle spasms. At any point during this process, a suitable narcotic can be administered that will dramatically reverse the withdrawal symptoms. Major withdrawal symptoms peak between 48 and 96 hours after the last dose and subside after about 8 to 12 days. Sudden withdrawal by heavily dependent users who are in poor health is very rarely fatal. Morphine withdrawal is considered less dangerous than alcohol, barbiturate, or benzodiazepine withdrawal.^[25]

The psychological dependence associated with morphine addiction is complex and protracted. Long after the physical need for morphine has passed, the addict will usually continue to think and talk about the use of morphine (or other drugs) and feel strange or overwhelmed coping with daily activities without being under the influence of morphine. Psychological withdrawal from morphine is a very long and painful process.^[26] Addicts often suffer severe depression, anxiety, insomnia, mood swings, amnesia (forgetfulness), low self-esteem, confusion, paranoia, and other psychological disorders. The psychological dependence on morphine can, and usually does, last a lifetime.^[27] There is a high probability that relapse will occur after morphine withdrawal when neither the physical environment nor the behavioral motivators that contributed to the abuse have been altered. Testimony to morphine's addictive and reinforcing nature is its relapse rate. Abusers of morphine (and heroin), have the highest relapse rates among all drug users, including abusers of other opioids, cocaine, and methamphetamine.^{[citation needed]} A complication that may arise from long-term morphine use or abuse is neurotoxicity. Morphine is more often associated with nightmares where oxycodone is not. It is not fully understood yet exactly how morphine may cause neurotoxicity. Morphine neurotoxicity, such as delirium, resolves when rotating from morphine to oxycodone. Oxycodone's neurological side effects are more cognitive than motor (myoclonus) and hallucinations are reported less frequently with oxycodone than with morphine.[2] ^[28] It is possible that these effects arise from the stronger binding affinity of morphine to kappa receptors than oxycodone. This article is about the concept of addiction. ... An opioid is any agent that binds to opioid receptors found principally in the central nervous system and gastrointestinal tract. ... For other uses, see Cocaine (disambiguation). ... This article is about the psychostimulant, d-methamphetamine. ... Neurotoxicity occurs when the exposure to natural or manmade toxic substances ,which are called neurotoxins, alters the normal activity of the nervous system. ... Not to be confused with oxytocin. ...

Hepatitis C and morphine withdrawal

Researchers at the University of Pennsylvania have demonstrated that morphine withdrawal complicates hepatitis C by suppressing IFN-alpha-mediated immunity and enhancing virus replication. Hepatitis C virus (HCV) is common among intravenous drug users, with 70 to 80% of abusers infected in the United States.^{[citation needed]} This high association has piqued interest in determining the effects of drug abuse, specifically morphine and heroin, on progression of the disease. The discovery of such an association would impact treatment of both HCV infection and drug abuse.^[29] This page is for the disease. ...

Access to morphine in poor countries

Although morphine is cheap, people in poorer countries often do not have access to it. According to a 2005 estimate by the International Narcotics Control Board, six countries consume 79 percent of the world’s morphine. The less affluent countries, accounting for 80 percent of the world's population, consumed only about 6 percent of the global morphine supply. Some countries import virtually no morphine, and in others the drug is rarely available even for relieving severe pain while dying. Experts in pain management attribute the under-distribution of morphine to an unwarranted fear of the drug's potential for addiction and abuse. While morphine is clearly addictive, western doctors believe it is worthwhile to use the drug and then wean the patient off when the treatment is over.^[30] Mr. ...

Additional images

Animated model of the Morphine molecule Image File history File links No higher resolution available. ...

Morphine molecule space-fill model Image File history File links Size of this preview: 724 × 600 pixels Full resolution (1400 × 1160 pixel, file size: 485 KB, MIME type: image/png) File links The following pages on the English Wikipedia link to this file (pages on other projects are not listed): Morphine User:RedAndr ...

Morphine molecule ball and stick model Image File history File links Size of this preview: 611 × 600 pixelsFull resolution (2048 × 2010 pixel, file size: 994 KB, MIME type: image/png) File links The following pages on the English Wikipedia link to this file (pages on other projects are not listed): Morphine User:RedAndr ...

See also

Wikinews has related news:

2005 Afghan opium harvest begins

• Alphamethylfentanyl
• Cheese (recreational drug)
• Diacetyldihydromorphine
• Dihydromorphine
• Dipropanoylmorphine
• Drug addiction
• Drug injection
• Drugs and prostitution
• Entomotoxicology
• Etorphine
• Heroin
• Illegal drug trade
• Methadone
• Monoacetylmorphine
• Opioid
• Opium
• Opium licensing
• Opium poppy
• Polish heroin
• Psychoactive drug
• Recreational drug use

Image File history File links WikiNews-Logo. ... Wikinews is a free-content news source and a project of the Wikimedia Foundation. ... α-methylfentanyl is an opioid analgesic that is an analogue of fentanyl. ... Example of cheese, seized by the U.S. Drug Enforcement Administration. ... Diacetyldihydromorphine (Paralaudin, Dihydroheroin) is a potent opiate derivative which is rarely used in some countries for the treatment of strong pain such as that caused by terminal cancer, as a more potent form of diamorphine. ... Dihydromorphine is a semi-synthetic opioid invented in Germany in the first years of the twentieth century. ... Dipropanoylmorphine is the 3,6-dipropanoyl ester of morphine, CAS number 10589-79-4. ... Drug addiction, or dependency is the compulsive use of drugs, to the point where the user has no effective choice but to continue use. ... This article does not cite any references or sources. ... Drugs and prostitution are related in that some drug addicts, most commonly heroin or crack cocaine users, obtain their drugs primarily through prostitution. ... Etorphine (Immobilon or M99) is a semi-synthetic opioid possessing an analgesic potency approximately 10,000 times that of morphine and was first prepared in 1960 from oripavine, which does not generally occur in opium poppy extract but rather in poppy straw and in related plants, Papaver orientale and Papaver... Heroin (INN: diacetylmorphine, BAN: diamorphine) is a semi-synthetic opioid synthesized from morphine, a derivative of the opium poppy. ... Panamanian motor vessel Gatun during the largest cocaine bust in United States Coast Guard history (20 tons), off the coast of Panama. ... Methadone (Dolophine, Amidone, Methadose, Physeptone, Heptadon and many others) is a synthetic opioid, used medically as an analgesic, antitussive and a maintenance anti-addictive for use in patients on opioids. ... 6-monoacetylmorphine (6-MAM) is one of 2 active metabolites of heroin (diacetylmorphine), the other being the much less active 3-monoacetylmorphine (3-MAM). ... An opioid is a chemical substance that has a morphine-like action in the body. ... This article is about the drug. ... Opium licensing is a policy instrument used to counter illegal drug cultivation and production. ... Binomial name L. The opium poppy, Papaver somniferum, is the type of poppy from which opium and all refined opiates such as morphine, thebaine, codeine, papaverine, and noscapine are extracted. ... Man shooting kompot. Also known as kompot or compote, this is a highly addictive drug which is used mainly in eastern Europe. ... An assortment of psychoactive drugs A psychoactive drug or psychotropic substance is a chemical substance that acts primarily upon the central nervous system where it alters brain function, resulting in temporary changes in perception, mood, consciousness and behavior. ... Recreational drug use is the use of psychoactive drugs for recreational purposes rather than for work, medical or spiritual purposes, although the distinction is not always clear. ...

References