PHENELZINE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C8H12N2
Molecular Weight	136.1943
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

NNCCC1=CC=CC=C1

InChI

InChIKey=RMUCZJUITONUFY-UHFFFAOYSA-N

InChI=1S/C8H12N2/c9-10-7-6-8-4-2-1-3-5-8/h1-5,10H,6-7,9H2

HIDE SMILES / InChI

Description
Sources: http://www.drugbank.ca/drugs/DB00780
Curator's Comment: Description was created based on several sources, including https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/011909s038lbl.pdf

Phenelzine is an irreversible non-selective inhibitor of monoamine oxidase. 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. Phenelzine is used for the treatment of major depressive disorder. Has also been used with some success in the management of bulimia nervosa.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Monoamine oxidase A 49 Target ID: CHEMBL1951 Sources: http://www.drugbank.ca/drugs/DB00780	Inhibitor 8146
Monoamine oxidase B 72 Target ID: CHEMBL2039 Sources: http://www.drugbank.ca/drugs/DB00780	Inhibitor 8146
Monoamine oxidase B 72 Target ID: CHEMBL2993 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11591508	Inhibitor 8146	76.3 nM [IC50]
Monoamine oxidase A 49 Target ID: CHEMBL3358 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11591508	Inhibitor 8146	30.0 nM [IC50]
Cytochrome P450 2C19 51 Target ID: CHEMBL3622 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16669850	Inhibitor 8146
Cytochrome P450 3A 22 Target ID: CHEMBL2364675 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16669850	Inhibitor 8146

Conditions

Condition	Modality	Targets	Highest Phase	Product
Depression 232 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/011909s038lbl.pdf	Primary		Approved 8307	Nardil Approved Use Nardil is used for: Treating depression in patients who do not respond well to other medicines. Launch Date -2.70345601E11

C_max

Value	Dose	Co-administered	Analyte	Population
10.14 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/27085800	15 mg single, oral dose: 15 mg route of administration: Oral experiment type: SINGLE co-administered:		PHENELZINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
19.8 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/011909s038lbl.pdf	30 mg single, oral dose: 30 mg route of administration: Oral experiment type: SINGLE co-administered:		PHENELZINE plasma	Homo sapiens population: UNKNOWN age: ADULT sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
384.2 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/27085800	15 mg single, oral dose: 15 mg route of administration: Oral experiment type: SINGLE co-administered:		PHENELZINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
9.75 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/27085800	15 mg single, oral dose: 15 mg route of administration: Oral experiment type: SINGLE co-administered:		PHENELZINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
11.6 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/011909s038lbl.pdf	30 mg single, oral dose: 30 mg route of administration: Oral experiment type: SINGLE co-administered:		PHENELZINE plasma	Homo sapiens population: UNKNOWN age: ADULT sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
750 mg single, oral Overdose Dose: 750 mg Route: oral Route: single Dose: 750 mg Sources: https://pubmed.ncbi.nlm.nih.gov/14489944	unhealthy, 20 n = 1 Health Status: unhealthy Condition: Depression Age Group: 20 Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/14489944	Disc. AE: Weakness, Lethargy... AEs leading to discontinuation/dose reduction: Weakness Lethargy Dizziness Gait abnormal NOS Restlessness Grand mal seizure Hyperreflexia Coma Depression central nervous system Sources: https://pubmed.ncbi.nlm.nih.gov/14489944
2760 mg single, oral Overdose Dose: 2760 mg Route: oral Route: single Dose: 2760 mg Co-administed with:: olanzapine, p.o(50 mg; single) Sources: https://pubmed.ncbi.nlm.nih.gov/17823790 Page: p.1007	unhealthy, 23 n = 1 Health Status: unhealthy Condition: Depression Age Group: 23 Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/17823790 Page: p.1007	Disc. AE: Depressed level of consciousness, Seizures... AEs leading to discontinuation/dose reduction: Depressed level of consciousness Seizures Tachycardia Acute myocarditis (grade 5) Sources: https://pubmed.ncbi.nlm.nih.gov/17823790 Page: p.1007
225 mg single, oral Overdose Dose: 225 mg Route: oral Route: single Dose: 225 mg Sources: https://pubmed.ncbi.nlm.nih.gov/6391305 Page: p.1137/99	unhealthy, 26 n = 1 Health Status: unhealthy Condition: Depression Age Group: 26 Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/6391305 Page: p.1137/99	Disc. AE: Muscular tone excessive, Hyperthermia... AEs leading to discontinuation/dose reduction: Muscular tone excessive Hyperthermia (severe) Coma Cardiovascular collapse Acute renal failure Hemolysis Rhabdomyolysis Disseminated intravascular coagulation Sources: https://pubmed.ncbi.nlm.nih.gov/6391305 Page: p.1137/99
90 mg 1 times / day multiple, oral Recommended Dose: 90 mg, 1 times / day Route: oral Route: multiple Dose: 90 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/011909s038lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Depression Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/011909s038lbl.pdf Page: p.1	Disc. AE: Suicidal ideation... AEs leading to discontinuation/dose reduction: Suicidal ideation Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/011909s038lbl.pdf Page: p.1
90 mg 1 times / day multiple, oral Recommended Dose: 90 mg, 1 times / day Route: oral Route: multiple Dose: 90 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/011909s038lbl.pdf Page: p.6	unhealthy Health Status: unhealthy Condition: Depression Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/011909s038lbl.pdf Page: p.6	Disc. AE: Crisis hypertensive... AEs leading to discontinuation/dose reduction: Crisis hypertensive Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/011909s038lbl.pdf Page: p.6

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1532	inhibitor 1695	inhibitor 1789	inhibitor 1570

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2C8 869 CYP1A2 1463 CYP2C19 1410 CYP3A 208 CYP3A5 73 CYP3A7 7 CYP2A6 670 CYP2E1 846 P-gp 1401 BSEP 392 OATP1B1 770 OATP1B3 691

Drug as perpetrator

Target	Modality	Activity
CYP2A6 702	inhibitor 3185 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkw1MjgyIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDEwODkifX0%3D	no [IC50 >10 uM]
CYP2E1 929	inhibitor 3185 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkw1MjgxIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDEwODkifX0%3D	no [IC50 >10 uM]
P-gp 1588	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/16997908/	no
BSEP 393	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/22961681/	unlikely [IC50 >897.2 uM]
CYP2C8 923	inhibitor 3185 Sources: https://go.drugbank.com/drugs/DB00780\| https://www.guidetopharmacology.org/GRAC/LigandDisplayForward?tab=biology&ligandId=7266	yes [Ki 1.2 uM]
CYP1A2 1620	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/16669850/\| https://pubmed.ncbi.nlm.nih.gov/22931300/	yes
CYP2C19 1484	inhibitor 3185 Sources: https://go.drugbank.com/drugs/DB00780\| https://pubmed.ncbi.nlm.nih.gov/16669850/, https://pubmed.ncbi.nlm.nih.gov/22931300/	yes
CYP2C9 1747	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/16669850/\| https://pubmed.ncbi.nlm.nih.gov/22931300/	yes
CYP2D6 1826	inhibitor 3185 Sources: https://go.drugbank.com/drugs/DB00780\| https://pubmed.ncbi.nlm.nih.gov/16669850/, https://pubmed.ncbi.nlm.nih.gov/22931300/	yes
CYP3A 291	inhibitor 3185 Sources: https://go.drugbank.com/drugs/DB00780\| https://pubmed.ncbi.nlm.nih.gov/16669850/	yes
CYP3A4 1857	inhibitor 3185 Sources: https://go.drugbank.com/drugs/DB00780\| https://pubmed.ncbi.nlm.nih.gov/22931300/	yes
CYP3A5 130	inhibitor 3185 Sources: https://go.drugbank.com/drugs/DB00780 \| https://pubmed.ncbi.nlm.nih.gov/16669850/	yes
CYP3A7 22	inhibitor 3185 Sources: https://go.drugbank.com/drugs/DB00780 \| https://pubmed.ncbi.nlm.nih.gov/16669850/	yes
OATP1B1 785	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/23571415/	yes
OATP1B3 700	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/23571415/	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1603	inhibitor 1584 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwyNDAiLCJ1c2VfY3VzdG9tX3F1ZXJ5Ijp0cnVlLCJzZWFyY2hfdGVybSI6IiIsInRleHRfZmlsdGVyIjoiQ0hFTUJMMTA4OSJ9fQ%3D%3D

Sourcing

Vendor/Aggregator	ID	URL
3B Scientific (Wuhan) Corp	3B3-036093	http://www.3bsc.com/index/pro_info.php?id=58125
AA Blocks	AA00I926	https://www.aablocks.com/goods/Goods/detail?id=AA00I926
AHH Chemical co.,ltd	MT-20901	http://www.ahhchemical.com/product/MT-20901.html
AK Scientific, Inc. (AKSCI)	4752AE	http://www.aksci.com/item_detail.php?cat=4752AE
Alfa Chemistry	51-71-8	https://www.alfa-chemistry.com/phenelzine-cas-51-71-8-item-168473.htm
Alichem	250001552	http://www.alichem.com/en/products/51-71-8.html
Ambinter	Amb1117029	http://www.ambinter.com/reference/1117029
Angel Pharmatech	AG199778	http://www.angelpharmatech.com/51-71-8.html
Angene	AGN-PC-0JK6MF	http://www.angenechemical.com/productshow/AGN-PC-0JK6MF.html
Aurora Fine Chemicals LLC	A00.215.116	http://online.aurorafinechemicals.com/info?ID=A00.215.116
BLD Pharm	BD44517	http://www.bldpharm.com/products/51-71-8.html
CSNpharm	CSN16899	https://www.csnpharm.com/products/phenelzine.html
Capot Chemical	16246	http://www.capotchem.com/en/16246.htm
Capot Chemical	PubChem16246	http://www.capotchem.com/en/16246.htm
Chem Scene	CS-4532	http://www.chemscene.com/51-71-8.html
ChemMol	49417192	http://www.chemmol.com/chemmol/49417192.html
Debye Scientific	DB-052010	http://www.debyesci.com/cas_51-71-8.html
Finetech	FT-0631225	http://www.finetechnology-ind.com/prod/detail/pub/51-71-8.html
Hairui	HR100277	http://www.hairuichem.com/en/product/51-71-8.html
Lab Network	LN00126164	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN00126164
Matrix Scientific	20638	https://www.matrixscientific.com/020638.html
MedChem Express	HY-B1018	https://www.medchemexpress.com/Phenelzine.html
MuseChem	I003863	https://www.musechem.com/product/I003863.html
OChem	4816	http://www.ocheminc.com/index.php?act=psearch&pid=047P825
Sigma-Aldrich	CDS021446_ALDRICH	https://www.sigmaaldrich.com/catalog/product/aldrich/cds021446?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Sinfoo Biotech	S017495	http://www.sinfoobiotech.com/product/1020893
Smolecule	S568415	https://www.smolecule.com/products/s568415
THE BioTek	bt-315150	https://www.thebiotek.com/product/others/bt-315150
abcr GmbH	AB200546	http://www.abcr.com/shop/en/AB200546
iChemical	EBD46347	http://www.ichemical.com/products/51-71-8.html?utm_source=PubChem&utm_medium=website&utm_campaign=product%20catalogs
mcule	MCULE-2911295500	https://mcule.com/MCULE-2911295500/

PubMed

Title	Date	PubMed
Phenelzine associated peripheral neuropathy--clinical and electrophysiologic findings.	1991 Jun	1659356
Depression after cyproheptadine: MAO treatment.	1992 Jun 1	1525285
Phenylethylidenehydrazine, a novel GABA-transaminase inhibitor, reduces epileptiform activity in rat hippocampal slices.	2004	15207360
Mechanism-based inactivation of human cytochrome P4502C8 by drugs in vitro.	2004 Dec	15304522
[Neurobiology and pharmacotherapy of social phobia].	2004 Jul-Aug	15538306
Hypericum perforatum L (St John's wort) preferentially increases extracellular dopamine levels in the rat prefrontal cortex.	2004 Jun	15148244
Efficacy of quality criteria to identify potentially harmful information: a cross-sectional survey of complementary and alternative medicine web sites.	2004 Jun 29	15249270
Efficacy and tolerability of tranylcypromine versus phenelzine: a double-blind study in antidepressant-refractory depressed inpatients.	2004 Nov	15554763
Effect of antidepressants on GABA(B) receptor function and subunit expression in rat hippocampus.	2004 Oct 15	15451391
Monoamine oxidase inhibitors, their structural analogues, and neuroprotection.	2004 Sep	15462176
Modafinil augmentation of phenelzine for residual fatigue in dysthymia.	2004 Sep	15337670
Contribution of sleep research to the development of new antidepressants.	2005	16416706
Sleep and psychiatry.	2005	16416705
Neuroendocrine predictors of the evolution of depression.	2005	16156385
In vivo evidence for reduced cortical glutamate-glutamine cycling in rats treated with the antidepressant/antipanic drug phenelzine.	2005	16154287
Herb-drug interactions: a literature review.	2005	15916450
Social anxiety disorder : current treatment recommendations.	2005	15907150
Screening antidepressants in the chick separation-stress paradigm.	2005 Aug	15778882
Validity of sudden gains in acute phase treatment of depression.	2005 Feb	15709845
Brainstem levels of transcription factor AP-2 in rat are changed after treatment with phenelzine, but not with citalopram.	2005 Jan 21	15663788
Shy-Drager syndrome: multisystem atrophy with comorbid depression.	2005 Jan-Feb	15765825
A microarray study of MPP+-treated PC12 Cells: Mechanisms of toxicity (MOT) analysis using bioinformatics tools.	2005 Jul 15	16026605
Inhibition of monoamine oxidase-A activity in rat brain by synthetic hydrazines: structure-activity relationship (SAR).	2005 Jun	16119198
Remission rates with 3 consecutive antidepressant trials: effectiveness for depressed outpatients.	2005 Jun	15960558
Chronic treatment with the monoamine oxidase inhibitor phenelzine increases hypothalamic-pituitary-adrenocortical activity in male C57BL/6 mice: relevance to atypical depression.	2005 Mar	15564336
Cytochrome p450 enzymes mechanism based inhibitors: common sub-structures and reactivity.	2005 Oct	16248836
A selective test for antidepressant treatments using rats bred for stress-induced reduction of motor activity in the swim test.	2005 Oct	16047194
Traumatic stress: effects on the brain.	2006	17290802
Pharmacotherapy of social anxiety disorder: what does the evidence tell us?	2006	17092192
Antidepressants reverse corticosterone-mediated decrease in brain-derived neurotrophic factor expression: differential regulation of specific exons by antidepressants and corticosterone.	2006	16500030
Use of antidepressant medications in relation to the incidence of breast cancer.	2006 Apr 10	16523201
Monoamine oxidase inhibitors allow locomotor and rewarding responses to nicotine.	2006 Aug	16395299
Serotonin syndrome from the interaction of cyclobenzaprine with other serotoninergic drugs.	2006 Dec	17122225
Rapid identification of P-glycoprotein substrates and inhibitors.	2006 Dec	16997908
The effect of antidepressants on glucose homeostasis and insulin sensitivity: synthesis and mechanisms.	2006 Jan	16370964
Treatment of depression with atypical features: a meta-analytic approach.	2006 Jan 30	16321446
Effects of monoamine oxidase inhibitors on cocaine discrimination in rats.	2006 Mar	16495723
Quetiapine for insomnia associated with refractory depression exacerbated by phenelzine.	2006 Mar	16478812
An evaluation of potential mechanism-based inactivation of human drug metabolizing cytochromes P450 by monoamine oxidase inhibitors, including isoniazid.	2006 May	16669850
Transdermal selegiline: the new generation of monoamine oxidase inhibitors.	2006 May	16641841
Leading the way: advances in the diagnosis, treatment, and management of neuropsychiatric illnesses.	2006 May	16641838
Tamoxifen protect against hydroxyl radical generation induced by phenelzine in rat striatum.	2006 May 1	16500014
13C magnetic resonance spectroscopy studies of alterations in glutamate neurotransmission.	2006 May 15	16199016
Increased nicotine self-administration following prenatal exposure in female rats.	2006 Nov	17196243
Modeling anxiety-like states: pharmacological characterization of the chick separation stress paradigm.	2006 Nov	17021390
Aldehyde load in ischemia-reperfusion brain injury: neuroprotection by neutralization of reactive aldehydes with phenelzine.	2006 Nov 29	17026969
Sustained effects of phenelzine and tranylcypromine on orthostatic challenge in antidepressant-refractory depression.	2006 Oct	16974207
Antidepressants and inflammatory bowel disease: a systematic review.	2006 Sep 20	16984660
Antidepressant therapy in tinnitus.	2007 Apr	16973315
Successful use of phenelzine in treatment-resistant panic disorder.	2007 Feb	17335337

Patents

Sample Use Guides

In Vivo Use Guide

Initial dose: The usual starting dose of NARDIL is one tablet (15 mg) three times a day. Early phase treatment: Dosage should be increased to at least 60 mg per day at a fairly rapid pace consistent with patient tolerance. It may be necessary to increase dosage up to 90 mg per day to obtain sufficient MAO inhibition. Many patients do not show a clinical response until treatment at 60 mg has been continued for at least 4 weeks.

Route of Administration: Oral

In Vitro Use Guide

20 uM of Phenelzine inactivated all human liver microsomal CYP (CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A) but were most potent toward CYP3A and CYP2C19

Name

Type

Language

PHENELZINE

Official Name

English

PHENETHYLHYDRAZINE

Systematic Name

English

HYDRAZINE, (2-PHENYLETHYL)-

Systematic Name

English

PHENELZINE [VANDF]

Common Name

English

PHENELZINE [MI]

Common Name

English

Phenelzine [WHO-DD]

Common Name

English

phenelzine [INN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C667