You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on DrugBank.
Identification
NameEtorphine
Accession NumberDB01497
TypeSmall Molecule
GroupsIllicit, Vet Approved
Description

A narcotic analgesic morphinan used as a sedative in veterinary practice. In Hong Kong, Etorphine is regulated under Schedule 1 of Hong Kong’s Chapter 134 Dangerous Drugs Ordinance. It can only be used legally by health professionals and for university research purposes. The substance can be given by pharmacists under a prescription. In the US, Etorphine is listed as a Schedule I drug, although Etorphine hydrochloride is classified as Schedule II.

Structure
Thumb
Synonyms
Etorphinum
External Identifiers
  • DEA No. 9056
  • M99
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Etorphine Hydrochloride
Thumb
  • InChI Key: JNHPUZURWFYYHW-DTUSRQQPSA-N
  • Monoisotopic Mass: 447.217636288
  • Average Mass: 447.995
DBSALT000825
Categories
UNII42M2Y6NU9O
CAS number14521-96-1
WeightAverage: 411.5338
Monoisotopic: 411.240958549
Chemical FormulaC25H33NO4
InChI KeyInChIKey=CAHCBJPUTCKATP-HBDRVVKHSA-N
InChI
InChI=1S/C25H33NO4/c1-5-8-22(2,28)17-14-23-9-10-25(17,29-4)21-24(23)11-12-26(3)18(23)13-15-6-7-16(27)20(30-21)19(15)24/h6-7,9-10,17-18,21,27-28H,5,8,11-14H2,1-4H3/t17?,18-,21?,22?,23-,24+,25?/m1/s1
IUPAC Name
(1R,2R,6S)-19-(2-hydroxypentan-2-yl)-15-methoxy-3-methyl-13-oxa-3-azahexacyclo[13.2.2.1²,⁸.0¹,⁶.0⁶,¹⁴.0⁷,¹²]icosa-7,9,11,16-tetraen-11-ol
SMILES
[H][C@]12CC3=C4C(OC5[C@@]4(CCN1C)[C@]21CC(C(C)(O)CCC)C5(OC)C=C1)=C(O)C=C3
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as morphinans. These are polycyclic compounds with a four-ring skeleton with three condensed six-member rings forming a partially hydrogenated phenanthrene moiety, one of which is aromatic while the two others are alicyclic.
KingdomOrganic compounds
Super ClassAlkaloids and derivatives
ClassMorphinans
Sub ClassNot Available
Direct ParentMorphinans
Alternative Parents
Substituents
  • Morphinan
  • Benzylisoquinoline
  • Phenanthrene
  • Tetralin
  • Azaspirodecane
  • Benzofuran
  • Aralkylamine
  • Alkyl aryl ether
  • Benzenoid
  • Piperidine
  • Tertiary alcohol
  • Tertiary aliphatic amine
  • Tertiary amine
  • Oxacycle
  • Azacycle
  • Organoheterocyclic compound
  • Ether
  • Dialkyl ether
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Amine
  • Alcohol
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationNot Available
PharmacodynamicsEtorphine is a synthetic cousin of morphine and 40,000 times more powerful. It can be produced from thebaine. It is most often used to immobilize elephants and other large mammals. Etorphine is only available legally for veterinary use and is strictly governed by law.
Mechanism of actionEtorphine is an agonist at mu, delta, and kappa opioid receptors. It also has a weak affinity for the ORL1 nociceptin/orphanin FQ receptor.
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9954
Blood Brain Barrier+0.9708
Caco-2 permeable+0.7322
P-glycoprotein substrateSubstrate0.9173
P-glycoprotein inhibitor IInhibitor0.7399
P-glycoprotein inhibitor IINon-inhibitor0.7779
Renal organic cation transporterNon-inhibitor0.6479
CYP450 2C9 substrateNon-substrate0.8713
CYP450 2D6 substrateSubstrate0.7349
CYP450 3A4 substrateSubstrate0.7858
CYP450 1A2 substrateNon-inhibitor0.9392
CYP450 2C9 inhibitorNon-inhibitor0.8992
CYP450 2D6 inhibitorNon-inhibitor0.6197
CYP450 2C19 inhibitorNon-inhibitor0.8553
CYP450 3A4 inhibitorNon-inhibitor0.8272
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9294
Ames testNon AMES toxic0.7862
CarcinogenicityNon-carcinogens0.9372
BiodegradationNot ready biodegradable0.9973
Rat acute toxicity3.2955 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8072
hERG inhibition (predictor II)Non-inhibitor0.7219
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point214-217 °CPhysProp
logP2.79SANGSTER (1993)
Predicted Properties
PropertyValueSource
Water Solubility0.112 mg/mLALOGPS
logP3.29ALOGPS
logP2.47ChemAxon
logS-3.6ALOGPS
pKa (Strongest Acidic)7.48ChemAxon
pKa (Strongest Basic)11.72ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area62.16 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity116.51 m3·mol-1ChemAxon
Polarizability45.55 Å3ChemAxon
Number of Rings6ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis ReferenceNot Available
General ReferencesNot Available
External Links
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

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. Agonist binding to the receptor induces coupling to an inactive GDP-bound heterotrimeric G-protein complex and subsequent exchange of GDP for GTP in the G-protein alpha subunit leading to dissociati...
Gene Name:
OPRM1
Uniprot ID:
P35372
Molecular Weight:
44778.855 Da
References
  1. Duttaroy A, Yoburn BC: In vivo regulation of mu-opioid receptor density and gene expression in CXBK and outbred Swiss Webster mice. Synapse. 2000 Aug;37(2):118-24. [PubMed:10881033 ]
  2. Melone M, Brecha NC, Sternini C, Evans C, Conti F: Etorphine increases the number of mu-opioid receptor-positive cells in the cerebral cortex. Neuroscience. 2000;100(3):439-43. [PubMed:11098106 ]
  3. Stafford K, Gomes AB, Shen J, Yoburn BC: mu-Opioid receptor downregulation contributes to opioid tolerance in vivo. Pharmacol Biochem Behav. 2001 May-Jun;69(1-2):233-7. [PubMed:11420091 ]
  4. Gomes BA, Shen J, Stafford K, Patel M, Yoburn BC: Mu-opioid receptor down-regulation and tolerance are not equally dependent upon G-protein signaling. Pharmacol Biochem Behav. 2002 May;72(1-2):273-8. [PubMed:11900797 ]
  5. Patel MB, Patel CN, Rajashekara V, Yoburn BC: Opioid agonists differentially regulate mu-opioid receptors and trafficking proteins in vivo. Mol Pharmacol. 2002 Dec;62(6):1464-70. [PubMed:12435815 ]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
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 nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling leads to the inhibition of adenylate cyclase activity. Inhibits neurot...
Gene Name:
OPRD1
Uniprot ID:
P41143
Molecular Weight:
40368.235 Da
References
  1. Li JG, Benovic JL, Liu-Chen LY: Mechanisms of agonist-induced down-regulation of the human kappa-opioid receptor: internalization is required for down-regulation. Mol Pharmacol. 2000 Oct;58(4):795-801. [PubMed:10999950 ]
  2. Li JG, Zhang F, Jin XL, Liu-Chen LY: Differential regulation of the human kappa opioid receptor by agonists: etorphine and levorphanol reduced dynorphin A- and U50,488H-induced internalization and phosphorylation. J Pharmacol Exp Ther. 2003 May;305(2):531-40. Epub 2003 Jan 24. [PubMed:12606694 ]
  3. Marie N, Lecoq I, Jauzac P, Allouche S: Differential sorting of human delta-opioid receptors after internalization by peptide and alkaloid agonists. J Biol Chem. 2003 Jun 20;278(25):22795-804. Epub 2003 Apr 2. [PubMed:12672796 ]
  4. Sumner BE, Douglas AJ, Russell JA: Pregnancy alters the density of opioid binding sites in the supraoptic nucleus and posterior pituitary gland of rats. Neurosci Lett. 1992 Mar 30;137(2):216-20. [PubMed:1316589 ]
  5. Tao PL, Tsai CL, Chang LR, Loh HH: Chronic effect of [D-Pen2,D-Pen5]enkephalin on rat brain opioid receptors. Eur J Pharmacol. 1991 Aug 29;201(2-3):209-14. [PubMed:1665782 ]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
  7. Niwa M, al-Essa LY, Ohta S, Kohno K, Nozaki M, Tsurumi K, Iwamura T, Kataoka T: Opioid receptor interaction and adenylyl cyclase inhibition of dihydroetorphine: direct comparison with etorphine. Life Sci. 1995;56(21):PL395-400. [PubMed:7739347 ]
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 synthetic opioids and for the psychoactive diterpene salvinorin A. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates th...
Gene Name:
OPRK1
Uniprot ID:
P41145
Molecular Weight:
42644.665 Da
References
  1. Niwa M, al-Essa LY, Ohta S, Kohno K, Nozaki M, Tsurumi K, Iwamura T, Kataoka T: Opioid receptor interaction and adenylyl cyclase inhibition of dihydroetorphine: direct comparison with etorphine. Life Sci. 1995;56(21):PL395-400. [PubMed:7739347 ]
  2. Wannemacher KM, Yadav PN, Howells RD: A select set of opioid ligands induce up-regulation by promoting the maturation and stability of the rat kappa-opioid receptor in human embryonic kidney 293 cells. J Pharmacol Exp Ther. 2007 Nov;323(2):614-25. Epub 2007 Aug 24. [PubMed:17720886 ]
  3. Gharagozlou P, Hashemi E, DeLorey TM, Clark JD, Lameh J: Pharmacological profiles of opioid ligands at kappa opioid receptors. BMC Pharmacol. 2006 Jan 25;6:3. [PubMed:16433932 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
agonist
General Function:
Nociceptin receptor activity
Specific Function:
G-protein coupled opioid receptor that functions as receptor for the endogenous neuropeptide nociceptin. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Signaling via G proteins mediates inhibition of adenylate cyclase activity and calcium channel activity. Arrestins mod...
Gene Name:
OPRL1
Uniprot ID:
P41146
Molecular Weight:
40692.775 Da
References
  1. Hawkinson JE, Acosta-Burruel M, Espitia SA: Opioid activity profiles indicate similarities between the nociceptin/orphanin FQ and opioid receptors. Eur J Pharmacol. 2000 Feb 18;389(2-3):107-14. [PubMed:10688973 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
agonist
General Function:
Zinc ion binding
Specific Function:
E3 ubiquitin ligase involved in the retrotranslocation and turnover of membrane and secretory proteins from the ER through a set of processes named ER-associated degradation (ERAD). This process acts on misfolded proteins as well as in the regulated degradation of correctly folded proteins. Enhances ionizing radiation-induced p53/TP53 stability and apoptosis via ubiquitinating MDM2 and AKT1 and...
Gene Name:
TRIM13
Uniprot ID:
O60858
Molecular Weight:
46987.08 Da
References
  1. Maneckjee R, Archer S, Zukin RS: Characterization of a polyclonal antibody to the mu opioid receptor. J Neuroimmunol. 1988 Feb;17(3):199-208. [PubMed:2828423 ]
  2. Stojilkovic SS, Dufau ML, Catt KJ: Opiate receptor subtypes in the rat hypothalamus and neurointermediate lobe. Endocrinology. 1987 Jul;121(1):384-94. [PubMed:3036471 ]
  3. Pesce G, Lang MA, Russell JT, Rodbard D, Gainer H: Characterization of kappa opioid receptors in neurosecretosomes from bovine posterior pituitary. J Neurochem. 1987 Aug;49(2):421-7. [PubMed:3037028 ]
  4. Pfeiffer A, Herz A: Discrimination of three opiate receptor binding sites with the use of a computerized curve-fitting technique. Mol Pharmacol. 1982 Mar;21(2):266-71. [PubMed:6124875 ]
  5. Audigier Y, Mazarguil H, Gout R, Cros J: Structure-activity relationships of enkephalin analogs at opiate and enkephalin receptors: correlation with analgesia. Eur J Pharmacol. 1980 Apr 11;63(1):35-46. [PubMed:6247160 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Type 4 melanocortin receptor binding
Specific Function:
ACTH stimulates the adrenal glands to release cortisol.MSH (melanocyte-stimulating hormone) increases the pigmentation of skin by increasing melanin production in melanocytes.Beta-endorphin and Met-enkephalin are endogenous opiates.
Gene Name:
POMC
Uniprot ID:
P01189
Molecular Weight:
29423.72 Da
References
  1. Sanchez-Blazquez P, Garzon J: Further characterization of alpha N-acetyl beta-endorphin-(1-31) regulatory activity, I: Effect on opioid- and alpha 2-mediated supraspinal antinociception in mice. Life Sci. 1992;50(26):2083-97. [PubMed:1318989 ]
  2. Xu JY, Fujimoto JM, Tseng LF: Involvement of supraspinal epsilon and mu opioid receptors in inhibition of the tail-flick response induced by etorphine in the mouse. J Pharmacol Exp Ther. 1992 Oct;263(1):246-52. [PubMed:1328609 ]
  3. Nicolas P, Li CH: Beta-endorphin-(1-27) is a naturally occurring antagonist to etorphine-induced analgesia. Proc Natl Acad Sci U S A. 1985 May;82(10):3178-81. [PubMed:2987913 ]
  4. Dum J, Gramsch C, Herz A: Activation of hypothalamic beta-endorphin pools by reward induced by highly palatable food. Pharmacol Biochem Behav. 1983 Mar;18(3):443-7. [PubMed:6132412 ]
  5. Lemaire S, Livett B, Tseng R, Mercier P, Lemaire I: Studies on the inhibitory action of opiate compounds in isolated bovine adrenal chromaffin cells: noninvolvement of stereospecific opiate binding sites. J Neurochem. 1981 Mar;36(3):886-92. [PubMed:6259293 ]
Comments
comments powered by Disqus
Drug created on July 31, 2007 07:09 / Updated on September 16, 2013 17:14