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Identification
NamePhenmetrazine
Accession NumberDB00830  (APRD00262)
TypeSmall Molecule
GroupsApproved, Illicit
Description

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

Structure
Thumb
Synonyms
SynonymLanguageCode
2-Phenyl-3-methylmorpholineNot AvailableNot Available
FenmetrazinNot AvailableNot Available
FenmetrazinaSpanishINN
PhenmetrazinNot AvailableNot Available
PhenmetrazinumLatinINN
Prescription ProductsNot Available
Generic Prescription ProductsNot Available
Over the Counter ProductsNot Available
International Brands
NameCompany
PreludinNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Phenmetrazine hydrochloride
Thumb
  • InChI Key: VJNXVAVKCZJOFQ-UHFFFAOYNA-N
  • Monoisotopic Mass: 213.092041846
  • Average Mass: 213.704
DBSALT000705
Categories
CAS number134-49-6
WeightAverage: 177.2429
Monoisotopic: 177.115364107
Chemical FormulaC11H15NO
InChI KeyOOBHFESNSZDWIU-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
Taxonomy
DescriptionThis 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.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassOxazinanes
Sub ClassMorpholines
Direct ParentPhenylmorpholines
Alternative Parents
Substituents
  • Phenylmorpholine
  • Aralkylamine
  • Benzenoid
  • Monocyclic benzene moiety
  • Oxacycle
  • Azacycle
  • Secondary amine
  • Ether
  • Secondary aliphatic amine
  • Dialkyl ether
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Amine
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationUsed as an anorectic in the treatment of obesity.
PharmacodynamicsPhenmetrazine 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 actionPhenmetrazine 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.
AbsorptionReadily absorbed from the gastro-intestinal tract and buccal mucosa.
Volume of distributionNot Available
Protein bindingNot 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 eliminationNot Available
Half life16 to 31 hours
ClearanceNot Available
ToxicityAdult 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
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
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 substrateNon-inhibitor0.9188
CYP450 2D6 substrateNon-inhibitor0.6846
CYP450 2C19 substrateNon-inhibitor0.7002
CYP450 3A4 substrateNon-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
Pharmacoeconomics
Manufacturers
  • Boehringer ingelheim pharmaceuticals inc
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point139 °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 RuleYesChemAxon
Spectra
Mass Spec (NIST)Download (8.5 KB)
SpectraMS
References
Synthesis ReferenceNot Available
General ReferenceNot Available
External Links
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSDownload (285 KB)
Interactions
Drug Interactions
Drug
AminophyllineMay enhance the adverse/toxic effect of other Sympathomimetics.
AmphetamineMay enhance the adverse/toxic effect of other Sympathomimetics.
ArformoterolMay enhance the adverse/toxic effect of other Sympathomimetics.
armodafinilMay enhance the adverse/toxic effect of other Sympathomimetics.
ArticaineMay enhance the adverse/toxic effect of other Sympathomimetics.
AtomoxetineAtoMOXetine may enhance the hypertensive effect of Sympathomimetics. AtoMOXetine may enhance the tachycardic effect of Sympathomimetics.
BenzphetamineMay enhance the adverse/toxic effect of other Sympathomimetics.
CaffeineMay enhance the adverse/toxic effect of other Sympathomimetics.
CocaineMay enhance the adverse/toxic effect of other Sympathomimetics.
DexmethylphenidateMay enhance the adverse/toxic effect of other Sympathomimetics.
DextroamphetamineMay enhance the adverse/toxic effect of other Sympathomimetics.
DiethylpropionMay enhance the adverse/toxic effect of other Sympathomimetics.
DihydrocodeineMay enhance the adverse/toxic effect of other Sympathomimetics.
DipivefrinMay enhance the adverse/toxic effect of other Sympathomimetics.
DobutamineMay enhance the adverse/toxic effect of other Sympathomimetics.
DopamineMay enhance the adverse/toxic effect of other Sympathomimetics.
DoxapramMay enhance the adverse/toxic effect of other Sympathomimetics.
DronabinolCannabinoid-Containing Products may enhance the tachycardic effect of Sympathomimetics.
FenoterolMay enhance the adverse/toxic effect of other Sympathomimetics.
Fluticasone furoateMay enhance the adverse/toxic effect of other Sympathomimetics.
FormoterolMay enhance the adverse/toxic effect of other Sympathomimetics.
IndacaterolMay enhance the adverse/toxic effect of other Sympathomimetics.
IobenguaneMay diminish the therapeutic effect of Iobenguane I 123.
Ipratropium bromideMay enhance the adverse/toxic effect of other Sympathomimetics.
IsomethepteneMay enhance the adverse/toxic effect of other Sympathomimetics.
LevonordefrinMay enhance the adverse/toxic effect of other Sympathomimetics.
LinezolidLinezolid may enhance the hypertensive effect of Sympathomimetics.
LisdexamfetamineMay enhance the adverse/toxic effect of other Sympathomimetics.
MethamphetamineMay enhance the adverse/toxic effect of other Sympathomimetics.
MethylphenidateMay enhance the adverse/toxic effect of other Sympathomimetics.
MidodrineMay enhance the adverse/toxic effect of other Sympathomimetics.
ModafinilMay enhance the adverse/toxic effect of other Sympathomimetics.
NabiloneCannabinoid-Containing Products may enhance the tachycardic effect of Sympathomimetics.
NaphazolineMay enhance the adverse/toxic effect of other Sympathomimetics.
NorepinephrineMay enhance the adverse/toxic effect of other Sympathomimetics.
OrciprenalineMay enhance the adverse/toxic effect of other Sympathomimetics.
OxymetazolineMay enhance the adverse/toxic effect of other Sympathomimetics.
PhendimetrazineMay enhance the adverse/toxic effect of other Sympathomimetics.
PheniramineMay enhance the adverse/toxic effect of other Sympathomimetics.
PhentermineMay enhance the adverse/toxic effect of other Sympathomimetics.
PhenylephrineMay enhance the adverse/toxic effect of other Sympathomimetics.
PirbuterolMay enhance the adverse/toxic effect of other Sympathomimetics.
PropylhexedrineMay enhance the adverse/toxic effect of other Sympathomimetics.
PseudoephedrineMay enhance the adverse/toxic effect of other Sympathomimetics.
SalbutamolMay enhance the adverse/toxic effect of other Sympathomimetics.
SalmeterolMay enhance the adverse/toxic effect of other Sympathomimetics.
Tedizolid PhosphateTedizolid may enhance the hypertensive effect of Sympathomimetics. Tedizolid may enhance the tachycardic effect of Sympathomimetics.
TerbutalineMay enhance the adverse/toxic effect of other Sympathomimetics.
TheophyllineMay enhance the adverse/toxic effect of other Sympathomimetics.
TriprolidineMay enhance the adverse/toxic effect of other Sympathomimetics.
Food InteractionsNot Available

Targets

1. Sodium-dependent noradrenaline transporter

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Sodium-dependent noradrenaline transporter P23975 Details

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
  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
  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
  4. Rothman RB, Baumann MH: Therapeutic potential of monoamine transporter substrates. Curr Top Med Chem. 2006;6(17):1845-59. Pubmed

2. Sodium-dependent dopamine transporter

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Sodium-dependent dopamine transporter Q01959 Details

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
  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
  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
  4. Rothman RB, Baumann MH: Therapeutic potential of monoamine transporter substrates. Curr Top Med Chem. 2006;6(17):1845-59. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:12