Tmic
You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on Toxin, Toxin Target Database.
Record Information
Version2.0
Creation Date2009-07-21 20:27:38 UTC
Update Date2014-12-24 20:25:52 UTC
Accession NumberT3D2889
Identification
Common NamePhenelzine
ClassSmall Molecule
DescriptionPhenelzine is only found in individuals that have used or taken this drug. It is an irreversible non-selective inhibitor of monoamine oxidase. May be used to treat major depressive disorder.Although the exact mechanism of action has not been determined, it appears that the irreversible, nonselective inhibition of MAO by phenelzine relieves depressive symptoms by causing an increase in the levels of serotonin, norepinephrine, and dopamine in the neuron.
Compound Type
  • Amine
  • Antidepressant
  • Antidepressive Agent
  • Drug
  • Hydrazine
  • Metabolite
  • Monoamine Oxidase Inhibitor
  • Organic Compound
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
Alazine
Fenelzina
Margyl
Monofen
Nardelzine
Nardil
Phenelzin
Phénelzine
Phenelzine Sulfate
Phenelzinum
β-Phenylethylhydrazine
Chemical FormulaC8H12N2
Average Molecular Mass136.194 g/mol
Monoisotopic Mass136.100 g/mol
CAS Registry Number51-71-8
IUPAC Name(2-phenylethyl)hydrazine
Traditional Namephenelzine
SMILESNNCCC1=CC=CC=C1
InChI IdentifierInChI=1S/C8H12N2/c9-10-7-6-8-4-2-1-3-5-8/h1-5,10H,6-7,9H2
InChI KeyInChIKey=RMUCZJUITONUFY-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as benzene and substituted derivatives. These are aromatic compounds containing one monocyclic ring system consisting of benzene.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassNot Available
Direct ParentBenzene and substituted derivatives
Alternative Parents
Substituents
  • Monocyclic benzene moiety
  • Alkylhydrazine
  • Organic nitrogen compound
  • Organopnictogen compound
  • Hydrocarbon derivative
  • Organonitrogen compound
  • Hydrazine derivative
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateLiquid
AppearanceNot Available
Experimental Properties
PropertyValue
Melting Point< 25°C
Boiling Point74°C at 1.00E-01 mm Hg
Solubility29.1 g/L
LogP1.1
Predicted Properties
PropertyValueSource
Water Solubility11.1 g/LALOGPS
logP1.2ALOGPS
logP1.2ChemAxon
logS-1.1ALOGPS
pKa (Strongest Basic)5.55ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area38.05 ŲChemAxon
Rotatable Bond Count3ChemAxon
Refractivity54.26 m³·mol⁻¹ChemAxon
Polarizability15.8 ųChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-0a4l-9800000000-fec970db2245559d8531View in MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-0a4l-9800000000-fec970db2245559d8531View in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0007-9200000000-b2c57d1368223a96c523View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-01t9-0592000000-92a48c620c961fdb430fView in MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-0a4i-0900000000-cf09dbe619ab21f16ce0View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-000i-0900000000-6c9dda205486ea199582View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0a4i-1900000000-d6caecbd05b28ce80778View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-052f-9200000000-e6be767f746d7eec77baView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-000i-1900000000-97c518b056fc3f0c5992View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-000i-4900000000-6d2d5af23910f83be107View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0kx3-9600000000-9577503e15a41993941bView in MoNA
MSMass Spectrum (Electron Ionization)splash10-0002-9000000000-833e467e14c48ae4f6b3View in MoNA
Toxicity Profile
Route of ExposureReadily absorbed after oral administration.
Mechanism of ToxicityAlthough the exact mechanism of action has not been determined, it appears that the irreversible, nonselective inhibition of MAO by phenelzine relieves depressive symptoms by causing an increase in the levels of serotonin, norepinephrine, and dopamine in the neuron.
MetabolismHepatic. Acetylation of phenelzine appears to be a minor metabolic pathway. Beta-phenylethylamine is a metabolite of phenelzine, and there is indirect evidence that phenelzine may also be ring-hydroxylated and N-methylated. Route of Elimination: NARDIL® is extensively metabolized, primarily by oxidation via monoamine oxidase. Half Life: 1.2-11.6 hours following single dose administration. Multiple-dose pharmacokinetics have not been studied.
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)3, not classifiable as to its carcinogenicity to humans. (5)
Uses/SourcesFor the treatment of major depressive disorder. Has also been used with some success in the management of bulimia nervosa.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsSymptoms of overdose include drowsiness, dizziness, faintness, irritability, hyperactivity, agitation, severe headache, hallucinations, trismus, opisthotonos, convulsions and coma, rapid and irregular pulse, hypertension, hypotension and vascular collapse, precordial pain, respiratory depression and failure, hyperpyrexia, diaphoresis, and cool, clammy skin.
TreatmentIntensive symptomatic and supportive treatment may be required. Induction of emesis or gastric lavage with instillation of charcoal slurry may be helpful in early poisoning, provided the airway has been protected against aspiration. Signs and symptoms of central nervous system stimulation, including convulsions, should be treated with diazepam, given slowly intravenously. Phenothiazine derivatives and central nervous system stimulants should be avoided. Hypotension and vascular collapse should be treated with intravenous fluids and, if necessary, blood pressure titration with an intravenous infusion of dilute pressor agent. It should be noted that adrenergic agents may produce a markedly increased pressor response. Respiration should be supported by appropriate measures, including management of the airway, use of supplemental oxygen, and mechanical ventilatory assistance, as required. Body temperature should be monitored closely. Intensive management of hyperpyrexia may be required. Maintenance of fluid and electrolyte balance is essential. (4)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00780
HMDB IDHMDB14918
PubChem Compound ID3675
ChEMBL IDCHEMBL1089
ChemSpider ID3547
KEGG IDC07430
UniProt IDNot Available
OMIM ID
ChEBI ID248018
BioCyc IDNot Available
CTD IDNot Available
Stitch IDPhenelzine
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkPhenelzine
References
Synthesis ReferenceNot Available
MSDST3D2889.pdf
General References
  1. Nolen WA: [Classical monoamine oxidase inhibitor: not registered for, but still a place in the treatment of depression]. Ned Tijdschr Geneeskd. 2003 Oct 4;147(40):1940-3. [14574774 ]
  2. Sowa BN, Holt A, Todd KG, Baker GB: Monoamine oxidase inhibitors, their structural analogues, and neuroprotection. Indian J Exp Biol. 2004 Sep;42(9):851-7. [15462176 ]
  3. Drugs.com [Link]
  4. RxList: The Internet Drug Index (2009). [Link]
  5. International Agency for Research on Cancer (2014). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

General Function:
Succinate-semialdehyde dehydrogenase binding
Specific Function:
Catalyzes the conversion of gamma-aminobutyrate and L-beta-aminoisobutyrate to succinate semialdehyde and methylmalonate semialdehyde, respectively. Can also convert delta-aminovalerate and beta-alanine.
Gene Name:
ABAT
Uniprot ID:
P80404
Molecular Weight:
56438.405 Da
References
  1. MacKenzie EM, Grant SL, Baker GB, Wood PL: Phenelzine causes an increase in brain ornithine that is prevented by prior monoamine oxidase inhibition. Neurochem Res. 2008 Mar;33(3):430-6. Epub 2007 Aug 31. [17768678 ]
  2. Tanay VA, Parent MB, Wong JT, Paslawski T, Martin IL, Baker GB: Effects of the antidepressant/antipanic drug phenelzine on alanine and alanine transaminase in rat brain. Cell Mol Neurobiol. 2001 Aug;21(4):325-39. [11775064 ]
  3. McKenna KF, McManus DJ, Baker GB, Coutts RT: Chronic administration of the antidepressant phenelzine and its N-acetyl analogue: effects on GABAergic function. J Neural Transm Suppl. 1994;41:115-22. [7931216 ]
  4. McManus DJ, Baker GB, Martin IL, Greenshaw AJ, McKenna KF: Effects of the antidepressant/antipanic drug phenelzine on GABA concentrations and GABA-transaminase activity in rat brain. Biochem Pharmacol. 1992 Jun 9;43(11):2486-9. [1610412 ]
  5. Todd KG, Baker GB: GABA-elevating effects of the antidepressant/antipanic drug phenelzine in brain: effects of pretreatment with tranylcypromine, (-)-deprenyl and clorgyline. J Affect Disord. 1995 Dec 13;35(3):125-9. [8749840 ]
  6. Todd KG, Baker GB: Neurochemical effects of the monoamine oxidase inhibitor phenelzine on brain GABA and alanine: A comparison with vigabatrin. J Pharm Pharm Sci. 2008 May 16;11(2):14s-21s. [19203467 ]
  7. McKenna KF, Baker GB, Coutts RT: N2-acetylphenelzine: effects on rat brain GABA, alanine and biogenic amines. Naunyn Schmiedebergs Arch Pharmacol. 1991 May;343(5):478-82. [1881457 ]
General Function:
Tryptamine:oxygen oxidoreductase (deaminating) activity
Specific Function:
Cell adhesion protein that participates in lymphocyte extravasation and recirculation by mediating the binding of lymphocytes to peripheral lymph node vascular endothelial cells in an L-selectin-independent fashion. Has semicarbazide-sensitive (SSAO) monoamine oxidase activity. May play a role in adipogenesis.
Gene Name:
AOC3
Uniprot ID:
Q16853
Molecular Weight:
84621.27 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC500.01995 uMNot AvailableBindingDB 50105417
References
  1. Tipnis UR, Tao M, Boor PJ: Purification and characterization of semicarbazide-sensitive amine oxidase from porcine aorta. Cell Mol Biol (Noisy-le-grand). 1992 Aug-Sep;38(5-6):575-84. [1483111 ]
  2. Holt A, Baker GB: Metabolism of agmatine (clonidine-displacing substance) by diamine oxidase and the possible implications for studies of imidazoline receptors. Prog Brain Res. 1995;106:187-97. [8584654 ]
  3. Kumar D, Trent MB, Boor PJ: Allylamine and beta-aminopropionitrile induced aortic medial necrosis: mechanisms of synergism. Toxicology. 1998 Feb 6;125(2-3):107-15. [9570326 ]
  4. Nurminen EM, Pihlavisto M, Lazar L, Szakonyi Z, Pentikainen U, Fulop F, Pentikainen OT: Synthesis, in vitro activity, and three-dimensional quantitative structure-activity relationship of novel hydrazine inhibitors of human vascular adhesion protein-1. J Med Chem. 2010 Sep 9;53(17):6301-15. doi: 10.1021/jm100337z. [20690686 ]
General Function:
Pyridoxal phosphate binding
Specific Function:
Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate. Participates in cellular nitrogen metabolism and also in liver gluconeogenesis starting with precursors transported from skeletal muscles (By similarity).
Gene Name:
GPT
Uniprot ID:
P24298
Molecular Weight:
54636.415 Da
References
  1. Todd KG, Baker GB: Neurochemical effects of the monoamine oxidase inhibitor phenelzine on brain GABA and alanine: A comparison with vigabatrin. J Pharm Pharm Sci. 2008 May 16;11(2):14s-21s. [19203467 ]
  2. Tanay VA, Parent MB, Wong JT, Paslawski T, Martin IL, Baker GB: Effects of the antidepressant/antipanic drug phenelzine on alanine and alanine transaminase in rat brain. Cell Mol Neurobiol. 2001 Aug;21(4):325-39. [11775064 ]
  3. McKenna KF, Baker GB, Coutts RT: N2-acetylphenelzine: effects on rat brain GABA, alanine and biogenic amines. Naunyn Schmiedebergs Arch Pharmacol. 1991 May;343(5):478-82. [1881457 ]
General Function:
Pyridoxal phosphate binding
Specific Function:
Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate.
Gene Name:
GPT2
Uniprot ID:
Q8TD30
Molecular Weight:
57903.11 Da
References
  1. Todd KG, Baker GB: Neurochemical effects of the monoamine oxidase inhibitor phenelzine on brain GABA and alanine: A comparison with vigabatrin. J Pharm Pharm Sci. 2008 May 16;11(2):14s-21s. [19203467 ]
  2. Tanay VA, Parent MB, Wong JT, Paslawski T, Martin IL, Baker GB: Effects of the antidepressant/antipanic drug phenelzine on alanine and alanine transaminase in rat brain. Cell Mol Neurobiol. 2001 Aug;21(4):325-39. [11775064 ]
  3. McKenna KF, Baker GB, Coutts RT: N2-acetylphenelzine: effects on rat brain GABA, alanine and biogenic amines. Naunyn Schmiedebergs Arch Pharmacol. 1991 May;343(5):478-82. [1881457 ]
General Function:
Transcription regulatory region dna binding
Specific Function:
Histone demethylase that demethylates both 'Lys-4' (H3K4me) and 'Lys-9' (H3K9me) of histone H3, thereby acting as a coactivator or a corepressor, depending on the context. Acts by oxidizing the substrate by FAD to generate the corresponding imine that is subsequently hydrolyzed. Acts as a corepressor by mediating demethylation of H3K4me, a specific tag for epigenetic transcriptional activation. Demethylates both mono- (H3K4me1) and di-methylated (H3K4me2) H3K4me. May play a role in the repression of neuronal genes. Alone, it is unable to demethylate H3K4me on nucleosomes and requires the presence of RCOR1/CoREST to achieve such activity. Also acts as a coactivator of androgen receptor (ANDR)-dependent transcription, by being recruited to ANDR target genes and mediating demethylation of H3K9me, a specific tag for epigenetic transcriptional repression. The presence of PRKCB in ANDR-containing complexes, which mediates phosphorylation of 'Thr-6' of histone H3 (H3T6ph), a specific tag that prevents demethylation H3K4me, prevents H3K4me demethylase activity of KDM1A. Demethylates di-methylated 'Lys-370' of p53/TP53 which prevents interaction of p53/TP53 with TP53BP1 and represses p53/TP53-mediated transcriptional activation. Demethylates and stabilizes the DNA methylase DNMT1. Required for gastrulation during embryogenesis. Component of a RCOR/GFI/KDM1A/HDAC complex that suppresses, via histone deacetylase (HDAC) recruitment, a number of genes implicated in multilineage blood cell development. Effector of SNAI1-mediated transcription repression of E-cadherin/CDH1, CDN7 and KRT8. Required for the maintenance of the silenced state of the SNAI1 target genes E-cadherin/CDH1 and CDN7.
Gene Name:
KDM1A
Uniprot ID:
O60341
Molecular Weight:
92901.905 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory17.6 uMNot AvailableBindingDB 50105417
Inhibitory18 uMNot AvailableBindingDB 50105417
References
  1. Lohse B, Kristensen JL, Kristensen LH, Agger K, Helin K, Gajhede M, Clausen RP: Inhibitors of histone demethylases. Bioorg Med Chem. 2011 Jun 15;19(12):3625-36. doi: 10.1016/j.bmc.2011.01.046. Epub 2011 Feb 1. [21596573 ]
  2. Suzuki T, Miyata N: Lysine demethylases inhibitors. J Med Chem. 2011 Dec 22;54(24):8236-50. doi: 10.1021/jm201048w. Epub 2011 Oct 7. [21955276 ]
General Function:
Serotonin binding
Specific Function:
Catalyzes the oxidative deamination of biogenic and xenobiotic amines and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral tissues. MAOA preferentially oxidizes biogenic amines such as 5-hydroxytryptamine (5-HT), norepinephrine and epinephrine.
Gene Name:
MAOA
Uniprot ID:
P21397
Molecular Weight:
59681.27 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
General Function:
Primary amine oxidase activity
Specific Function:
Catalyzes the oxidative deamination of biogenic and xenobiotic amines and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral tissues. MAOB preferentially degrades benzylamine and phenylethylamine.
Gene Name:
MAOB
Uniprot ID:
P27338
Molecular Weight:
58762.475 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
General Function:
Pyridoxal phosphate binding
Specific Function:
Not Available
Gene Name:
GAD65
Uniprot ID:
Q9UGI5
Molecular Weight:
47343.69 Da
References
  1. McKenna KF, McManus DJ, Baker GB, Coutts RT: Chronic administration of the antidepressant phenelzine and its N-acetyl analogue: effects on GABAergic function. J Neural Transm Suppl. 1994;41:115-22. [7931216 ]
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
Molecular Weight:
68494.255 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory8.4 uMNot AvailableBindingDB 50105417
References
  1. Tatsumi M, Groshan K, Blakely RD, Richelson E: Pharmacological profile of antidepressants and related compounds at human monoamine transporters. Eur J Pharmacol. 1997 Dec 11;340(2-3):249-58. [9537821 ]
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
Molecular Weight:
69331.42 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory>10 uMNot AvailableBindingDB 50105417
References
  1. Tatsumi M, Groshan K, Blakely RD, Richelson E: Pharmacological profile of antidepressants and related compounds at human monoamine transporters. Eur J Pharmacol. 1997 Dec 11;340(2-3):249-58. [9537821 ]
General Function:
Serotonin:sodium symporter activity
Specific Function:
Serotonin transporter whose primary function in the central nervous system involves the regulation of serotonergic signaling via transport of serotonin molecules from the synaptic cleft back into the pre-synaptic terminal for re-utilization. Plays a key role in mediating regulation of the availability of serotonin to other receptors of serotonergic systems. Terminates the action of serotonin and recycles it in a sodium-dependent manner.
Gene Name:
SLC6A4
Uniprot ID:
P31645
Molecular Weight:
70324.165 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory>10 uMNot AvailableBindingDB 50105417
References
  1. Tatsumi M, Groshan K, Blakely RD, Richelson E: Pharmacological profile of antidepressants and related compounds at human monoamine transporters. Eur J Pharmacol. 1997 Dec 11;340(2-3):249-58. [9537821 ]