Welcome to DrugBank 4.0! If you prefer, you can still go back to version 3.0.
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
FenmetrazinNot AvailableNot Available
FenmetrazinaSpanishINN
PhenmetrazinNot AvailableNot Available
PhenmetrazinumLatinINN
Salts
Name/CAS Structure Properties
Phenmetrazine hydrochloride
Thumb
  • InChI Key: VJNXVAVKCZJOFQ-UHFFFAOYNA-N
  • Monoisotopic Mass: 213.092041846
  • Average Mass: 213.704
DBSALT000705
Brand names
NameCompany
PreludinNot Available
Brand mixturesNot Available
Categories
CAS number134-49-6
WeightAverage: 177.2429
Monoisotopic: 177.115364107
Chemical FormulaC11H15NO
InChI KeyInChIKey=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
Mass Specshow(8.5 KB)
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassOxazinanes
SubclassMorpholines
Direct parentPhenylmorpholines
Alternative parentsBenzene and Substituted Derivatives; Dialkylamines; Dialkyl Ethers; Polyamines
Substituentsbenzene; secondary amine; secondary aliphatic amine; ether; dialkyl ether; polyamine; amine; organonitrogen compound
Classification descriptionThis compound belongs to the phenylmorpholines. These are aromatic compounds containing a morpholine ring and a benzene ring linked to each other through a CC or a CN bond.
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
Property Value Probability
Human Intestinal Absorption + 1.0
Blood Brain Barrier + 0.9723
Caco-2 permeable + 0.7082
P-glycoprotein substrate Substrate 0.5953
P-glycoprotein inhibitor I Non-inhibitor 0.7284
P-glycoprotein inhibitor II Non-inhibitor 0.9708
Renal organic cation transporter Inhibitor 0.5
CYP450 2C9 substrate Non-substrate 0.7859
CYP450 2D6 substrate Non-substrate 0.5985
CYP450 3A4 substrate Non-substrate 0.5798
CYP450 1A2 substrate Non-inhibitor 0.6065
CYP450 2C9 substrate Non-inhibitor 0.9188
CYP450 2D6 substrate Non-inhibitor 0.6846
CYP450 2C19 substrate Non-inhibitor 0.7002
CYP450 3A4 substrate Non-inhibitor 0.8524
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.7188
Ames test Non AMES toxic 0.8037
Carcinogenicity Non-carcinogens 0.9102
Biodegradation Not ready biodegradable 0.9538
Rat acute toxicity 2.6487 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.7603
hERG inhibition (predictor II) Non-inhibitor 0.7129
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 solubility2.44e+00 g/lALOGPS
logP1.45ALOGPS
logP1.79ChemAxon
logS-1.9ALOGPS
pKa (strongest basic)8.22ChemAxon
physiological charge1ChemAxon
hydrogen acceptor count2ChemAxon
hydrogen donor count1ChemAxon
polar surface area21.26ChemAxon
rotatable bond count1ChemAxon
refractivity52.47ChemAxon
polarizability20.1ChemAxon
number of rings2ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleYesChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis ReferenceNot Available
General ReferenceNot Available
External Links
ResourceLink
KEGG CompoundC07432
PubChem Compound4762
PubChem Substance46504524
ChemSpider4598
ChEBI8067
ChEMBL
Therapeutic Targets DatabaseDAP000860
PharmGKBPA164747188
WikipediaPhenmetrazine
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSshow(285 KB)
Interactions
Drug Interactions
Drug
ChlorpromazineDecreased anorexic effect, may increase psychotic symptoms
FluphenazineDecreased anorexic effect, may increase psychotic symptoms
GuanethidinePhenmetrazine may decrease the effect of guanethidine.
IsocarboxazidPossible hypertensive crisis
MesoridazineDecreased anorexic effect, may increase psychotic symptoms
MethotrimeprazineDecreased anorexic effect, may increase psychotic symptoms
PerphenazineDecreased anorexic effect, may increase psychotic symptoms
ProchlorperazineDecreased anorexic effect, may increase pyschotic symptoms
PromethazineDecreased anorexic effect, may increase pyschotic symptoms
PropericiazineDecreased anorexic effect, may increase pyschotic symptoms
RasagilinePossible hypertensive crisis
ThioridazineDecreased anorexic effect, may increase psychotic symptoms
TrifluoperazineDecreased anorexic effect, may increase psychotic symptoms
Food InteractionsNot Available

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

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