Phenmetrazine

Identification

Generic Name
Phenmetrazine
DrugBank Accession Number
DB00830
Background

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

Type
Small Molecule
Groups
Approved, Illicit
Structure
Weight
Average: 177.2429
Monoisotopic: 177.115364107
Chemical Formula
C11H15NO
Synonyms
  • 2-phenyl-3-methylmorpholine
  • Fenmetrazin
  • Fenmetrazina
  • Phenmetrazin
  • Phenmetrazine
  • Phenmetrazinum
External IDs
  • PAL-592
  • USAF Ge-1

Pharmacology

Indication

Used as an anorectic in the treatment of obesity.

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Contraindications & Blackbox Warnings
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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
Humans
ASodium-dependent dopamine transporter
inhibitor
Humans
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

Adverse Effects
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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.

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AcebutololPhenmetrazine may decrease the antihypertensive activities of Acebutolol.
AceclofenacThe risk or severity of hypertension can be increased when Phenmetrazine is combined with Aceclofenac.
AcemetacinThe risk or severity of hypertension can be increased when Phenmetrazine is combined with Acemetacin.
Acetylsalicylic acidThe risk or severity of hypertension can be increased when Phenmetrazine is combined with Acetylsalicylic acid.
AclidiniumThe risk or severity of Tachycardia can be increased when Phenmetrazine is combined with Aclidinium.
Food Interactions
Not Available

Products

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Product Ingredients
IngredientUNIICASInChI Key
Phenmetrazine hydrochloride6U85YRT5881707-14-8VJNXVAVKCZJOFQ-UHFFFAOYSA-N
International/Other Brands
Preludin

Categories

Drug Categories
Chemical TaxonomyProvided by Classyfire
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
Amine / Aralkylamine / Aromatic heteromonocyclic compound / Azacycle / Benzenoid / Dialkyl ether / Ether / Hydrocarbon derivative / Monocyclic benzene moiety / Organic nitrogen compound
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
morpholines (CHEBI:8067)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
XA501VL3VR
CAS number
134-49-6
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

References

General References
Not Available
Human Metabolome Database
HMDB0014968
KEGG Compound
C07432
PubChem Compound
4762
PubChem Substance
46504524
ChemSpider
4598
RxNav
8133
ChEBI
8067
ChEMBL
CHEMBL1201208
Therapeutic Targets Database
DAP000860
PharmGKB
PA164747188
Wikipedia
Phenmetrazine
MSDS
Download (285 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount

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-MSsplash10-0536-4900000000-7f843e150425b2270782
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/MSsplash10-004i-0900000000-7789f882858aebadb49a
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-004i-4900000000-f572c6e708475e0f8239
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-004i-2900000000-72e7c9f506f0016f8dd0
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-004l-8900000000-bb52d4be70eca73d7972
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-01r6-9500000000-34e2348883c5b626cf5f
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-0006-9400000000-3a70907adee561af31b9
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-004i-0900000000-7789f882858aebadb49a
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-004i-4900000000-f572c6e708475e0f8239
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-004i-2900000000-72e7c9f506f0016f8dd0
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-004l-8900000000-bb52d4be70eca73d7972
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-01r6-9500000000-34e2348883c5b626cf5f
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-0006-9400000000-3a70907adee561af31b9
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-143.7633236
predicted
DarkChem Lite v0.1.0
[M-H]-136.42412
predicted
DeepCCS 1.0 (2019)
[M-H]-143.7633236
predicted
DarkChem Lite v0.1.0
[M-H]-136.42412
predicted
DeepCCS 1.0 (2019)
[M+H]+144.6451236
predicted
DarkChem Lite v0.1.0
[M+H]+139.89934
predicted
DeepCCS 1.0 (2019)
[M+H]+144.6451236
predicted
DarkChem Lite v0.1.0
[M+H]+139.89934
predicted
DeepCCS 1.0 (2019)
[M+Na]+144.2170236
predicted
DarkChem Lite v0.1.0
[M+Na]+149.3134
predicted
DeepCCS 1.0 (2019)
[M+Na]+144.2170236
predicted
DarkChem Lite v0.1.0
[M+Na]+149.3134
predicted
DeepCCS 1.0 (2019)

Targets

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insights and accelerate drug research.
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Kind
Protein
Organism
Humans
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. [Article]
  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. [Article]
  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. [Article]
  4. Rothman RB, Baumann MH: Therapeutic potential of monoamine transporter substrates. Curr Top Med Chem. 2006;6(17):1845-59. [Article]
Kind
Protein
Organism
Humans
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. [Article]
  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. [Article]
  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. [Article]
  4. Rothman RB, Baumann MH: Therapeutic potential of monoamine transporter substrates. Curr Top Med Chem. 2006;6(17):1845-59. [Article]

Drug created at June 13, 2005 13:24 / Updated at March 03, 2024 02:33