Identification

Name
Phenmetrazine
Accession Number
DB00830  (APRD00262)
Type
Small Molecule
Groups
Approved, Illicit
Description

A sympathomimetic drug used primarily as an appetite depressant. Its actions and mechanisms are similar to dextroamphetamine. [PubChem]

Structure
Thumb
Synonyms
  • 2-Phenyl-3-methylmorpholine
  • Fenmetrazin
  • Fenmetrazina
  • Phenmetrazin
  • Phenmetrazinum
External IDs
PAL-592 / USAF Ge-1
Product Ingredients
IngredientUNIICASInChI Key
Phenmetrazine hydrochloride6U85YRT5881707-14-8VJNXVAVKCZJOFQ-UHFFFAOYNA-N
International/Other Brands
Preludin
Categories
UNII
XA501VL3VR
CAS number
134-49-6
Weight
Average: 177.2429
Monoisotopic: 177.115364107
Chemical Formula
C11H15NO
InChI Key
OOBHFESNSZDWIU-UHFFFAOYSA-N
InChI
InChI=1S/C11H15NO/c1-9-11(13-8-7-12-9)10-5-3-2-4-6-10/h2-6,9,11-12H,7-8H2,1H3
IUPAC Name
3-methyl-2-phenylmorpholine
SMILES
CC1NCCOC1C1=CC=CC=C1

Pharmacology

Indication

Used as an anorectic in the treatment of obesity.

Structured Indications
Not Available
Pharmacodynamics

Phenmetrazine is a sympathomimetic drug used primarily as an appetite depressant. Its actions and mechanisms are similar to dextroamphetamine. Amphetamines are non-catecholamine sympathomimetic amines with CNS stimulant activity. Phenmetrazine was originally sold under the tradename Preludin as an anorectic. It has since been removed from the market. It is by some considered to have a greater potential for addiction than the amphetamines, and has been abused in many countries, for example Sweden.

Mechanism of action

Phenmetrazine is thought to block the reuptake of norepinephrine and dopamine into the presynaptic neuron leading to an increase in the release of these monoamines into the extraneuronal space. Dopamine integrates incoming sensory stimuli, initiates and controls fine movement (nigro-neostriatal pathway), controls emotional behavior (midbrain mesolimbic-forebrain system) and controls hypothalamic-pituitary endocrine system (tubero-infundibular system). It is this latter effect on the tubero-infundibular systm that seems to lead to reduced food intake. Phenmetrazine also acts as a monoamine oxidase inhibitor.

TargetActionsOrganism
ASodium-dependent noradrenaline transporter
inhibitor
Human
ASodium-dependent dopamine transporter
inhibitor
Human
Absorption

Readily absorbed from the gastro-intestinal tract and buccal mucosa.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

Primarily hepatic (via CYP3A and CYP2D6). Resistant to metabolism by monoamine oxidase. Metabolism involves deamination to para-hydroxyamphetamine and phenylacetone; this latter compound is subsequently oxidize to benzoic acid and excreted as glucuronide or glycine (hippuric acid) conjugate. Smaller amounts of amphetamine are converted to norephedrine by oxidation.

Route of elimination
Not Available
Half life

16 to 31 hours

Clearance
Not Available
Toxicity

Adult monkeys have an LD50 of 15 to 20 mg/kg, whereas for young monkeys the LD50 is only 5 mg/kg. Symptoms of overdose include acute central nervous system stimulation, cardiotoxicity causing tachycardia, arrhythmias, hypertension, and cardiovascular collapse. Whilst some patients show signs of toxicity at blood concentrations of 20 µg/L, chronic abusers of amphetamine have been known to have blood concentration of up to 3000 µg/L.

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

Interactions

Drug Interactions
DrugInteractionDrug group
AcebutololThe risk or severity of adverse effects can be increased when Phenmetrazine is combined with Acebutolol.Approved
AmphetamineThe risk or severity of adverse effects can be increased when Amphetamine is combined with Phenmetrazine.Approved, Illicit
AtomoxetineAtomoxetine may increase the hypertensive activities of Phenmetrazine.Approved
BenzphetamineThe risk or severity of adverse effects can be increased when Phenmetrazine is combined with Benzphetamine.Approved, Illicit
BucindololThe risk or severity of adverse effects can be increased when Phenmetrazine is combined with Bucindolol.Investigational
CeliprololThe risk or severity of adverse effects can be increased when Phenmetrazine is combined with Celiprolol.Approved, Investigational
ChlorphentermineThe risk or severity of adverse effects can be increased when Phenmetrazine is combined with Chlorphentermine.Illicit, Withdrawn
ClenbuterolThe risk or severity of adverse effects can be increased when Phenmetrazine is combined with Clenbuterol.Approved, Vet Approved
DobutamineThe risk or severity of adverse effects can be increased when Phenmetrazine is combined with Dobutamine.Approved
DopamineThe risk or severity of adverse effects can be increased when Phenmetrazine is combined with Dopamine.Approved
DoxofyllineThe risk or severity of adverse effects can be increased when Phenmetrazine is combined with Doxofylline.Approved
DronabinolDronabinol may increase the tachycardic activities of Phenmetrazine.Approved, Illicit
EpanololThe risk or severity of adverse effects can be increased when Phenmetrazine is combined with Epanolol.Experimental
EphedrineThe risk or severity of adverse effects can be increased when Phenmetrazine is combined with Ephedrine.Approved
EpinephrineThe risk or severity of adverse effects can be increased when Epinephrine is combined with Phenmetrazine.Approved, Vet Approved
EtilefrineThe risk or severity of adverse effects can be increased when Phenmetrazine is combined with Etilefrine.Withdrawn
FenoterolThe risk or severity of adverse effects can be increased when Phenmetrazine is combined with Fenoterol.Approved
FenozoloneThe risk or severity of adverse effects can be increased when Phenmetrazine is combined with Fenozolone.Experimental
HydroxyamphetamineThe risk or severity of adverse effects can be increased when Phenmetrazine is combined with Hydroxyamphetamine.Approved
IobenguaneThe therapeutic efficacy of Iobenguane can be decreased when used in combination with Phenmetrazine.Approved
IsoprenalineThe risk or severity of adverse effects can be increased when Phenmetrazine is combined with Isoprenaline.Approved
IsoxsuprineThe risk or severity of adverse effects can be increased when Phenmetrazine is combined with Isoxsuprine.Approved, Withdrawn
LabetalolThe risk or severity of adverse effects can be increased when Labetalol is combined with Phenmetrazine.Approved
LinezolidLinezolid may increase the hypertensive activities of Phenmetrazine.Approved, Investigational
MefenorexThe risk or severity of adverse effects can be increased when Phenmetrazine is combined with Mefenorex.Experimental
MephentermineThe risk or severity of adverse effects can be increased when Phenmetrazine is combined with Mephentermine.Approved
MetaraminolThe risk or severity of adverse effects can be increased when Metaraminol is combined with Phenmetrazine.Approved, Investigational
MethamphetamineThe risk or severity of adverse effects can be increased when Phenmetrazine is combined with Methamphetamine.Approved, Illicit
MethoxamineThe risk or severity of adverse effects can be increased when Methoxamine is combined with Phenmetrazine.Approved
MidodrineThe risk or severity of adverse effects can be increased when Midodrine is combined with Phenmetrazine.Approved
NabiloneNabilone may increase the tachycardic activities of Phenmetrazine.Approved, Investigational
NorepinephrineThe risk or severity of adverse effects can be increased when Norepinephrine is combined with Phenmetrazine.Approved
NylidrinThe risk or severity of adverse effects can be increased when Phenmetrazine is combined with Nylidrin.Approved
OrciprenalineThe risk or severity of adverse effects can be increased when Orciprenaline is combined with Phenmetrazine.Approved
OxymetazolineThe risk or severity of adverse effects can be increased when Phenmetrazine is combined with Oxymetazoline.Approved
PhentermineThe risk or severity of adverse effects can be increased when Phentermine is combined with Phenmetrazine.Approved, Illicit
PhenylephrineThe risk or severity of adverse effects can be increased when Phenylephrine is combined with Phenmetrazine.Approved
PhenylpropanolamineThe risk or severity of adverse effects can be increased when Phenylpropanolamine is combined with Phenmetrazine.Approved, Vet Approved, Withdrawn
PrenalterolThe risk or severity of adverse effects can be increased when Phenmetrazine is combined with Prenalterol.Experimental
ProcaterolThe risk or severity of adverse effects can be increased when Phenmetrazine is combined with Procaterol.Approved
PseudoephedrineThe risk or severity of adverse effects can be increased when Phenmetrazine is combined with Pseudoephedrine.Approved
RacepinephrineThe risk or severity of adverse effects can be increased when Phenmetrazine is combined with Racepinephrine.Approved
RitodrineThe risk or severity of adverse effects can be increased when Phenmetrazine is combined with Ritodrine.Approved
SynephrineThe risk or severity of adverse effects can be increased when Phenmetrazine is combined with Synephrine.Experimental
Tedizolid PhosphateTedizolid Phosphate may increase the hypertensive activities of Phenmetrazine.Approved
TerbutalineThe risk or severity of adverse effects can be increased when Phenmetrazine is combined with Terbutaline.Approved
TetryzolineThe risk or severity of adverse effects can be increased when Phenmetrazine is combined with Tetryzoline.Approved
TramazolineThe risk or severity of adverse effects can be increased when Phenmetrazine is combined with Tramazoline.Investigational
TretoquinolThe risk or severity of adverse effects can be increased when Phenmetrazine is combined with Tretoquinol.Experimental
TyramineThe risk or severity of adverse effects can be increased when Phenmetrazine is combined with Tyramine.Investigational, Nutraceutical
Food Interactions
Not Available

References

Synthesis Reference
Not Available
General References
Not Available
External Links
Human Metabolome Database
HMDB14968
KEGG Compound
C07432
PubChem Compound
4762
PubChem Substance
46504524
ChemSpider
4598
ChEBI
8067
ChEMBL
CHEMBL1201208
Therapeutic Targets Database
DAP000860
PharmGKB
PA164747188
Wikipedia
Phenmetrazine
ATC Codes
Not Available
AHFS Codes
Not Available
PDB Entries
Not Available
FDA label
Not Available
MSDS
Download (285 KB)

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
  • Boehringer ingelheim pharmaceuticals inc
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)139 °CNot Available
water solubility>5 mg/LNot Available
logP1.7Not Available
Predicted Properties
PropertyValueSource
Water Solubility2.44 mg/mLALOGPS
logP1.45ALOGPS
logP1.79ChemAxon
logS-1.9ALOGPS
pKa (Strongest Basic)8.22ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area21.26 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity52.47 m3·mol-1ChemAxon
Polarizability20.1 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9723
Caco-2 permeable+0.7082
P-glycoprotein substrateSubstrate0.5953
P-glycoprotein inhibitor INon-inhibitor0.7284
P-glycoprotein inhibitor IINon-inhibitor0.9708
Renal organic cation transporterInhibitor0.5
CYP450 2C9 substrateNon-substrate0.7859
CYP450 2D6 substrateNon-substrate0.5985
CYP450 3A4 substrateNon-substrate0.5798
CYP450 1A2 substrateNon-inhibitor0.6065
CYP450 2C9 inhibitorNon-inhibitor0.9188
CYP450 2D6 inhibitorNon-inhibitor0.6846
CYP450 2C19 inhibitorNon-inhibitor0.7002
CYP450 3A4 inhibitorNon-inhibitor0.8524
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7188
Ames testNon AMES toxic0.8037
CarcinogenicityNon-carcinogens0.9102
BiodegradationNot ready biodegradable0.9538
Rat acute toxicity2.6487 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.7603
hERG inhibition (predictor II)Non-inhibitor0.7129
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Download (8.5 KB)
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
GC-MS Spectrum - EI-BGC-MSsplash10-00di-9100000000-da503eda1d0e6fdabb4c
Mass Spectrum (Electron Ionization)MSsplash10-05fu-9000000000-391e092b81a9d4597b70
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 phenylmorpholines. These are aromatic compounds containing a morpholine ring and a benzene ring linked to each other through a CC or a CN bond.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Oxazinanes
Sub Class
Morpholines
Direct Parent
Phenylmorpholines
Alternative Parents
Aralkylamines / Benzene and substituted derivatives / Oxacyclic compounds / Dialkylamines / Dialkyl ethers / Azacyclic compounds / Organopnictogen compounds / Hydrocarbon derivatives
Substituents
Phenylmorpholine / Aralkylamine / Monocyclic benzene moiety / Benzenoid / Dialkyl ether / Secondary aliphatic amine / Ether / Secondary amine / Azacycle / Oxacycle
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
morpholines (CHEBI:8067)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Norepinephrine:sodium symporter activity
Specific Function
Amine transporter. Terminates the action of noradrenaline by its high affinity sodium-dependent reuptake into presynaptic terminals.
Gene Name
SLC6A2
Uniprot ID
P23975
Uniprot Name
Sodium-dependent noradrenaline transporter
Molecular Weight
69331.42 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Rothman RB, Katsnelson M, Vu N, Partilla JS, Dersch CM, Blough BE, Baumann MH: Interaction of the anorectic medication, phendimetrazine, and its metabolites with monoamine transporters in rat brain. Eur J Pharmacol. 2002 Jun 28;447(1):51-7. [PubMed:12106802]
  4. Rothman RB, Baumann MH: Therapeutic potential of monoamine transporter substrates. Curr Top Med Chem. 2006;6(17):1845-59. [PubMed:17017961]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Monoamine transmembrane transporter activity
Specific Function
Amine transporter. Terminates the action of dopamine by its high affinity sodium-dependent reuptake into presynaptic terminals.
Gene Name
SLC6A3
Uniprot ID
Q01959
Uniprot Name
Sodium-dependent dopamine transporter
Molecular Weight
68494.255 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Rothman RB, Katsnelson M, Vu N, Partilla JS, Dersch CM, Blough BE, Baumann MH: Interaction of the anorectic medication, phendimetrazine, and its metabolites with monoamine transporters in rat brain. Eur J Pharmacol. 2002 Jun 28;447(1):51-7. [PubMed:12106802]
  4. Rothman RB, Baumann MH: Therapeutic potential of monoamine transporter substrates. Curr Top Med Chem. 2006;6(17):1845-59. [PubMed:17017961]

Drug created on June 13, 2005 07:24 / Updated on October 02, 2017 04:46