Identification

Name
3-Methylfentanyl
Accession Number
DB01571
Type
Small Molecule
Groups
Illicit
Description

3-Methylfentanyl (3-MF, mefentanyl) is an opioid analgesic that is an analogue of fentanyl. 3-Methylfentanyl is one of the most potent drugs that has been widely sold on the black market, estimated to be between 400-6000 times stronger than morphine depending on which isomer is used (with cis isomer being the more potent one). 3-Methylfentanyl was first discovered in 1974 and subsequently appeared on the street as an alternative to the clandestinely produced fentanyl analogue α-methylfentanyl. However it quickly became apparent that 3-methylfentanyl was much more potent than α-methylfentanyl, and corespondingly even more dangerous. [Wikipedia]

Structure
Thumb
Synonyms
  • 3-MF
  • mefentanyl
External IDs
DEA No. 9813
Categories
UNII
QVU94XE61A
CAS number
42045-86-3
Weight
Average: 350.4971
Monoisotopic: 350.235813592
Chemical Formula
C23H30N2O
InChI Key
MLQRZXNZHAOCHQ-UHFFFAOYSA-N
InChI
InChI=1S/C23H30N2O/c1-3-23(26)25(21-12-8-5-9-13-21)22-15-17-24(18-19(22)2)16-14-20-10-6-4-7-11-20/h4-13,19,22H,3,14-18H2,1-2H3
IUPAC Name
N-[3-methyl-1-(2-phenylethyl)piperidin-4-yl]-N-phenylpropanamide
SMILES
CCC(=O)N(C1CCN(CCC2=CC=CC=C2)CC1C)C1=CC=CC=C1

Pharmacology

Indication
Not Available
Pharmacodynamics

3-Methylfentanyl has similar effects to fentanyl, but is far more potent due to increased binding affinity to its target site. Since fentanyl itself is already highly potent, 3-methylfentanyl is extremely dangerous when used recreationally, and has resulted in many deaths among opiate addicts using the drug.

Mechanism of action

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. Fentanyl's analgesic activity is, most likely, due to its conversion to morphine. 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
AKappa-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

3-Methylfentanyl has resulted in many deaths among opiate addicts using the drug.

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

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
Not Available
External Links
PubChem Compound
61996
PubChem Substance
46509149
ChemSpider
55844
ChEBI
61092
Wikipedia
3-Methylfentanyl

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
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.015 mg/mLALOGPS
logP4.29ALOGPS
logP4.29ChemAxon
logS-4.4ALOGPS
pKa (Strongest Basic)9.08ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area23.55 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity107.9 m3·mol-1ChemAxon
Polarizability41.64 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9808
Blood Brain Barrier+0.9875
Caco-2 permeable+0.695
P-glycoprotein substrateSubstrate0.6788
P-glycoprotein inhibitor IInhibitor0.8087
P-glycoprotein inhibitor IINon-inhibitor0.735
Renal organic cation transporterInhibitor0.5413
CYP450 2C9 substrateNon-substrate0.8205
CYP450 2D6 substrateNon-substrate0.699
CYP450 3A4 substrateSubstrate0.6768
CYP450 1A2 substrateNon-inhibitor0.6901
CYP450 2C9 inhibitorNon-inhibitor0.8046
CYP450 2D6 inhibitorNon-inhibitor0.5713
CYP450 2C19 inhibitorNon-inhibitor0.7282
CYP450 3A4 inhibitorNon-inhibitor0.6426
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.6191
Ames testNon AMES toxic0.8872
CarcinogenicityNon-carcinogens0.8297
BiodegradationNot ready biodegradable0.9033
Rat acute toxicity2.9798 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8516
hERG inhibition (predictor II)Inhibitor0.6605
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 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
Phenethylamines / Anilides / Aralkylamines / Tertiary carboxylic acid amides / Trialkylamines / Amino acids and derivatives / Azacyclic compounds / Organopnictogen compounds / Organic oxides / Hydrocarbon derivatives
show 1 more
Substituents
Fentanyl / Phenethylamine / Anilide / Aralkylamine / Monocyclic benzene moiety / Benzenoid / Tertiary carboxylic acid amide / Amino acid or derivatives / Carboxamide group / Tertiary amine
show 13 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
piperidines, monocarboxylic acid amide (CHEBI:61092)

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. Subramanian G, Paterlini MG, Portoghese PS, Ferguson DM: Molecular docking reveals a novel binding site model for fentanyl at the mu-opioid receptor. J Med Chem. 2000 Feb 10;43(3):381-91. [PubMed:10669565]
  2. Jin WQ, Xu H, Zhu YC, Fang SN, Xia XL, Huang ZM, Ge BL, Chi ZQ: Studies on synthesis and relationship between analgesic activity and receptor affinity for 3-methyl fentanyl derivatives. Sci Sin. 1981 May;24(5):710-20. [PubMed:6264594]
  3. Wang ZX, Zhu YC, Chen XJ, Ji RY: [Stereoisomers of 3-methylfentanyl: synthesis, absolute configuration and analgesic activity]. Yao Xue Xue Bao. 1993;28(12):905-10. [PubMed:8030414]
  4. Zhu J, Yin J, Law PY, Claude PA, Rice KC, Evans CJ, Chen C, Yu L, Liu-Chen LY: Irreversible binding of cis-(+)-3-methylfentanyl isothiocyanate to the delta opioid receptor and determination of its binding domain. J Biol Chem. 1996 Jan 19;271(3):1430-4. [PubMed:8576134]
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. Jin WQ, Xu H, Zhu YC, Fang SN, Xia XL, Huang ZM, Ge BL, Chi ZQ: Studies on synthesis and relationship between analgesic activity and receptor affinity for 3-methyl fentanyl derivatives. Sci Sin. 1981 May;24(5):710-20. [PubMed:6264594]
  2. Wang ZX, Zhu YC, Chen XJ, Ji RY: [Stereoisomers of 3-methylfentanyl: synthesis, absolute configuration and analgesic activity]. Yao Xue Xue Bao. 1993;28(12):905-10. [PubMed:8030414]
  3. Zhu J, Yin J, Law PY, Claude PA, Rice KC, Evans CJ, Chen C, Yu L, Liu-Chen LY: Irreversible binding of cis-(+)-3-methylfentanyl isothiocyanate to the delta opioid receptor and determination of its binding domain. J Biol Chem. 1996 Jan 19;271(3):1430-4. [PubMed:8576134]
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. Jin WQ, Xu H, Zhu YC, Fang SN, Xia XL, Huang ZM, Ge BL, Chi ZQ: Studies on synthesis and relationship between analgesic activity and receptor affinity for 3-methyl fentanyl derivatives. Sci Sin. 1981 May;24(5):710-20. [PubMed:6264594]
  2. Wang ZX, Zhu YC, Chen XJ, Ji RY: [Stereoisomers of 3-methylfentanyl: synthesis, absolute configuration and analgesic activity]. Yao Xue Xue Bao. 1993;28(12):905-10. [PubMed:8030414]
  3. Zhu J, Yin J, Law PY, Claude PA, Rice KC, Evans CJ, Chen C, Yu L, Liu-Chen LY: Irreversible binding of cis-(+)-3-methylfentanyl isothiocyanate to the delta opioid receptor and determination of its binding domain. J Biol Chem. 1996 Jan 19;271(3):1430-4. [PubMed:8576134]

Drug created on July 31, 2007 07:10 / Updated on October 01, 2018 13:06