Identification

Name
Carfentanil
Accession Number
DB01535
Type
Small Molecule
Groups
Illicit, Investigational, Vet approved
Description

Carfentanil or carfentanyl (Wildnil) is an analogue of the popular synthetic opioid analgesic fentanyl, and is one of the most potent opioids known (also the most potent opioid used commercially). Carfentanil was first synthesized in 1974 by a team of chemists at Janssen Pharmaceutica which included Paul Janssen. It has a quantitative potency approximately 10,000 times that of morphine and 100 times that of fentanyl, with activity in humans starting at about 1 microgram. It is marketed under the trade name Wildnil as a general anaesthetic agent for large animals. Carfentanil is intended for large-animal use only as its extreme potency makes it inappropriate for use in humans. Currently sufentanil, approximately 10–20 times less potent (500 to 1000 times the efficacy of morphine per weight) than carfentanil, is the maximum strength fentanyl analog for use in humans.

Structure
Thumb
Synonyms
  • carfentanila
  • Carfentanyl
Product Ingredients
IngredientUNIICASInChI Key
Carfentanil citrate7LG286J8GV61380-27-6ZSLYVCXNFQPCGT-UHFFFAOYSA-N
Categories
UNII
LA9DTA2L8F
CAS number
59708-52-0
Weight
Average: 394.5066
Monoisotopic: 394.225642836
Chemical Formula
C24H30N2O3
InChI Key
YDSDEBIZUNNPOB-UHFFFAOYSA-N
InChI
InChI=1S/C24H30N2O3/c1-3-22(27)26(21-12-8-5-9-13-21)24(23(28)29-2)15-18-25(19-16-24)17-14-20-10-6-4-7-11-20/h4-13H,3,14-19H2,1-2H3
IUPAC Name
methyl 1-(2-phenylethyl)-4-(N-phenylpropanamido)piperidine-4-carboxylate
SMILES
CCC(=O)N(C1=CC=CC=C1)C1(CCN(CCC2=CC=CC=C2)CC1)C(=O)OC

Pharmacology

Indication

Carfentanil is similar (but more potent) to the opioid analgesic fentanyl. It is used as a tranquilizer for large animals.

Pharmacodynamics

Carfentanil acts primarily on the mu (some kappa and delta) opioid receptors as an agonist. It will induce similar effects of analgesia as other opioids, however, due to its potency, it will also induce strong side effects such as sedation. Consequently, that is why it is used as a tranquilizer for large animals.

Carfentanil interacts predominately with the opioid mu-receptor. These mu-binding sites are discretely distributed in the brain, spinal cord, and other tissues. It exerts its principal pharmacologic effects on the central nervous system. Its primary actions of therapeutic value are analgesia and sedation. Carfentanil also depresses the respiratory centers, depresses the cough reflex, and constricts the pupils.

Mechanism of action

Carfentanil binds very strongly to mu opioid receptors and acts as a competitive agonist. Opiate receptors are coupled with G-protein receptors and function as both positive and negative regulators of synaptic transmission via G-proteins that activate effector proteins. Binding of the opiate stimulates the exchange of GTP for GDP on the G-protein complex. As the effector system is adenylate cyclase and cAMP located at the inner surface of the plasma membrane, opioids decrease intracellular cAMP by inhibiting adenylate cyclase. Subsequently, the release of nociceptive neurotransmitters such as substance P, GABA, dopamine, acetylcholine and noradrenaline is inhibited. Opioids also inhibit the release of vasopressin, somatostatin, insulin and glucagon. Opioids close N-type voltage-operated calcium channels (OP2-receptor agonist) and open calcium-dependent inwardly rectifying potassium channels (OP3 and OP1 receptor agonist). This results in hyperpolarization and reduced neuronal excitability.

TargetActionsOrganism
AMu-type opioid receptor
agonist
Human
ADelta-type opioid receptor
agonist
Human
UKappa-type opioid receptor
agonist
Human
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
Not Available
Pathways
PathwayCategory
Carfentanil Action PathwayDrug action
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 Carfentanil.
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of serotonin syndrome can be increased when Carfentanil 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 Carfentanil.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of serotonin syndrome can be increased when 4-Bromo-2,5-dimethoxyamphetamine is combined with Carfentanil.
4-MethoxyamphetamineThe risk or severity of adverse effects can be increased when 4-Methoxyamphetamine is combined with Carfentanil.
5-methoxy-N,N-dimethyltryptamineThe risk or severity of serotonin syndrome can be increased when Carfentanil is combined with 5-methoxy-N,N-dimethyltryptamine.
7-NitroindazoleThe risk or severity of adverse effects can be increased when Carfentanil is combined with 7-Nitroindazole.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinolineThe risk or severity of serotonin syndrome can be increased when Carfentanil 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 Carfentanil.
AceprometazineThe risk or severity of hypotension and central nervous system depression can be increased when Aceprometazine is combined with Carfentanil.
Food Interactions
Not Available

References

Synthesis Reference

Louis P. Reiff, Paul B. Sollman, "Process of making carfentanil and related analgesics." U.S. Patent US5106983, issued January, 1981.

US5106983
General References
  1. Wax PM, Becker CE, Curry SC: Unexpected "gas" casualties in Moscow: a medical toxicology perspective. Ann Emerg Med. 2003 May;41(5):700-5. [PubMed:12712038]
External Links
PubChem Compound
62156
PubChem Substance
46505501
ChemSpider
55986
BindingDB
50012477
ChEBI
61084
ChEMBL
CHEMBL290429
Wikipedia
Carfentanil

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedScreeningSubstance-related Discorder1

Pharmacoeconomics

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

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0259 mg/mLALOGPS
logP3.7ALOGPS
logP3.67ChemAxon
logS-4.2ALOGPS
pKa (Strongest Basic)8.05ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area49.85 Å2ChemAxon
Rotatable Bond Count8ChemAxon
Refractivity114.38 m3·mol-1ChemAxon
Polarizability44.6 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.8605
Blood Brain Barrier+0.9762
Caco-2 permeable-0.5069
P-glycoprotein substrateSubstrate0.7011
P-glycoprotein inhibitor IInhibitor0.8424
P-glycoprotein inhibitor IINon-inhibitor0.6298
Renal organic cation transporterNon-inhibitor0.6504
CYP450 2C9 substrateNon-substrate0.8368
CYP450 2D6 substrateNon-substrate0.8791
CYP450 3A4 substrateSubstrate0.6667
CYP450 1A2 substrateNon-inhibitor0.9279
CYP450 2C9 inhibitorNon-inhibitor0.7664
CYP450 2D6 inhibitorNon-inhibitor0.8561
CYP450 2C19 inhibitorNon-inhibitor0.7325
CYP450 3A4 inhibitorNon-inhibitor0.6284
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.6023
Ames testNon AMES toxic0.7779
CarcinogenicityNon-carcinogens0.869
BiodegradationNot ready biodegradable0.9474
Rat acute toxicity2.9219 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9613
hERG inhibition (predictor II)Inhibitor0.6716
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 fentanyls. These are compounds containing the fentanyl moiety or a derivative, which is based on a N-(1-(2-phenylethyl)-4-piperidinyl)-N-phenylpropanamide skeleton.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Piperidines
Sub Class
Fentanyls
Direct Parent
Fentanyls
Alternative Parents
Alpha amino acids and derivatives / Piperidinecarboxylic acids / Phenethylamines / Anilides / Aralkylamines / Tertiary carboxylic acid amides / Methyl esters / Trialkylamines / Monocarboxylic acids and derivatives / Azacyclic compounds
show 4 more
Substituents
Fentanyl / Alpha-amino acid or derivatives / Phenethylamine / Piperidinecarboxylic acid / Anilide / Aralkylamine / Benzenoid / Monocyclic benzene moiety / Methyl ester / Tertiary carboxylic acid amide
show 18 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
piperidines, tertiary amino compound, methyl ester, carboxamide (CHEBI:61084)

Targets

Details
1. Mu-type opioid receptor
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. Bencherif B, Wand GS, McCaul ME, Kim YK, Ilgin N, Dannals RF, Frost JJ: Mu-opioid receptor binding measured by [11C]carfentanil positron emission tomography is related to craving and mood in alcohol dependence. Biol Psychiatry. 2004 Feb 1;55(3):255-62. [PubMed:14744466]
  2. Bencherif B, Stumpf MJ, Links JM, Frost JJ: Application of MRI-based partial-volume correction to the analysis of PET images of mu-opioid receptors using statistical parametric mapping. J Nucl Med. 2004 Mar;45(3):402-8. [PubMed:15001679]
  3. Jewett DM, Kilbourn MR: In vivo evaluation of new carfentanil-based radioligands for the mu opiate receptor. Nucl Med Biol. 2004 Apr;31(3):321-5. [PubMed:15028244]
  4. Mayberg HS, Sadzot B, Meltzer CC, Fisher RS, Lesser RP, Dannals RF, Lever JR, Wilson AA, Ravert HT, Wagner HN Jr, et al.: Quantification of mu and non-mu opiate receptors in temporal lobe epilepsy using positron emission tomography. Ann Neurol. 1991 Jul;30(1):3-11. [PubMed:1656846]
  5. Bartenstein PA, Prevett MC, Duncan JS, Hajek M, Wieser HG: Quantification of opiate receptors in two patients with mesiobasal temporal lobe epilepsy, before and after selective amygdalohippocampectomy, using positron emission tomography. Epilepsy Res. 1994 Jun;18(2):119-25. [PubMed:7957034]
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. Mayberg HS, Sadzot B, Meltzer CC, Fisher RS, Lesser RP, Dannals RF, Lever JR, Wilson AA, Ravert HT, Wagner HN Jr, et al.: Quantification of mu and non-mu opiate receptors in temporal lobe epilepsy using positron emission tomography. Ann Neurol. 1991 Jul;30(1):3-11. [PubMed:1656846]
  2. Barry U, Zuo Z: Opioids: old drugs for potential new applications. Curr Pharm Des. 2005;11(10):1343-50. [PubMed:15853689]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
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. Mayberg HS, Sadzot B, Meltzer CC, Fisher RS, Lesser RP, Dannals RF, Lever JR, Wilson AA, Ravert HT, Wagner HN Jr, et al.: Quantification of mu and non-mu opiate receptors in temporal lobe epilepsy using positron emission tomography. Ann Neurol. 1991 Jul;30(1):3-11. [PubMed:1656846]
  2. Barry U, Zuo Z: Opioids: old drugs for potential new applications. Curr Pharm Des. 2005;11(10):1343-50. [PubMed:15853689]

Drug created on July 31, 2007 07:10 / Updated on November 02, 2018 08:54