Identification

Name
Etorphine
Accession Number
DB01497
Type
Small Molecule
Groups
Illicit, 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
  • etorfina
  • Etorphine
  • Etorphinum
External IDs
DEA No. 9056 / M99
Product Ingredients
IngredientUNIICASInChI Key
Etorphine Hydrochloride8CBE01N74813764-49-3JNHPUZURWFYYHW-DTUSRQQPSA-N
Categories
UNII
42M2Y6NU9O
CAS number
14521-96-1
Weight
Average: 411.5338
Monoisotopic: 411.240958549
Chemical Formula
C25H33NO4
InChI Key
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

Pharmacology

Indication
Not Available
Pharmacodynamics

Etorphine 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 action

Etorphine is an agonist at mu, delta, and kappa opioid receptors. It also has a weak affinity for the ORL1 nociceptin/orphanin FQ receptor.

TargetActionsOrganism
AMu-type opioid receptor
agonist
Human
ADelta-type opioid receptor
agonist
Human
AKappa-type opioid receptor
agonist
Human
UNociceptin receptor
agonist
Human
UE3 ubiquitin-protein ligase TRIM13
agonist
Human
UPro-opiomelanocortinNot AvailableHuman
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
2,5-Dimethoxy-4-ethylamphetamineThe risk or severity of serotonin syndrome can be increased when 2,5-Dimethoxy-4-ethylamphetamine is combined with Etorphine.
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of serotonin syndrome can be increased when Etorphine is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3,4-MethylenedioxyamphetamineThe risk or severity of serotonin syndrome can be increased when Etorphine is combined with 3,4-Methylenedioxyamphetamine.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of serotonin syndrome can be increased when 4-Bromo-2,5-dimethoxyamphetamine is combined with Etorphine.
4-MethoxyamphetamineThe risk or severity of adverse effects can be increased when 4-Methoxyamphetamine is combined with Etorphine.
5-methoxy-N,N-dimethyltryptamineThe risk or severity of serotonin syndrome can be increased when Etorphine is combined with 5-methoxy-N,N-dimethyltryptamine.
7-NitroindazoleThe risk or severity of adverse effects can be increased when Etorphine is combined with 7-Nitroindazole.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinolineThe risk or severity of serotonin syndrome can be increased when Etorphine is combined with 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline.
AcepromazineThe risk or severity of hypotension and central nervous system depression can be increased when Acepromazine is combined with Etorphine.
AceprometazineThe risk or severity of hypotension and central nervous system depression can be increased when Aceprometazine is combined with Etorphine.
Food Interactions
Not Available

References

General References
Not Available
External Links
KEGG Compound
C11793
PubChem Compound
26721
PubChem Substance
46505591
ChemSpider
24895
ChEBI
4912
Therapeutic Targets Database
DNC000631
Wikipedia
Etorphine

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)214-217 °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 RuleNoChemAxon
MDDR-like RuleNoChemAxon
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)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This 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.
Kingdom
Organic compounds
Super Class
Alkaloids and derivatives
Class
Morphinans
Sub Class
Not Available
Direct Parent
Morphinans
Alternative Parents
Phenanthrenes and derivatives / Tetralins / Azaspirodecane derivatives / Coumarans / Aralkylamines / Alkyl aryl ethers / 1-hydroxy-2-unsubstituted benzenoids / Piperidines / Tertiary alcohols / Trialkylamines
show 5 more
Substituents
Morphinan / Phenanthrene / Azaspirodecane / Tetralin / Coumaran / Alkyl aryl ether / 1-hydroxy-2-unsubstituted benzenoid / Aralkylamine / Piperidine / Benzenoid
show 17 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not 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...
Gene Name
OPRM1
Uniprot ID
P35372
Uniprot Name
Mu-type opioid receptor
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 n...
Gene Name
OPRD1
Uniprot ID
P41143
Uniprot Name
Delta-type opioid receptor
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 synt...
Gene Name
OPRK1
Uniprot ID
P41145
Uniprot Name
Kappa-type opioid receptor
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-b...
Gene Name
OPRL1
Uniprot ID
P41146
Uniprot Name
Nociceptin receptor
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 ac...
Gene Name
TRIM13
Uniprot ID
O60858
Uniprot Name
E3 ubiquitin-protein ligase TRIM13
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...
Gene Name
POMC
Uniprot ID
P01189
Uniprot Name
Pro-opiomelanocortin
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]

Drug created on July 31, 2007 07:09 / Updated on December 14, 2018 12:40