Identification

Name
Pargyline
Accession Number
DB01626
Type
Small Molecule
Groups
Approved
Description

A monoamine oxidase inhibitor with antihypertensive properties. [PubChem]

Structure
Thumb
Synonyms
  • Eutonyl
  • Eutron
  • Pargyline
External IDs
Lopac-P-8013
Product Ingredients
IngredientUNIICASInChI Key
Pargyline hydrochlorideW70V6I2OMY306-07-0BCXCABRDBBWWGY-UHFFFAOYSA-N
International/Other Brands
Eutonyl
Categories
UNII
9MV14S8G3E
CAS number
555-57-7
Weight
Average: 159.2276
Monoisotopic: 159.104799421
Chemical Formula
C11H13N
InChI Key
DPWPWRLQFGFJFI-UHFFFAOYSA-N
InChI
InChI=1S/C11H13N/c1-3-9-12(2)10-11-7-5-4-6-8-11/h1,4-8H,9-10H2,2H3
IUPAC Name
benzyl(methyl)(prop-2-yn-1-yl)amine
SMILES
CN(CC#C)CC1=CC=CC=C1

Pharmacology

Indication

For the treatment of moderate to severe hypertension.

Pharmacodynamics

Pargyline is a monoamine oxidase B (MAO-B) inhibitor with antihypertensive properties. Patients taking pargyline must avoid concurrent consumption of tyramine-containing foods such as bleu cheese and beer, as this can lead to a hypertensive crisis.

Mechanism of action

MAOIs act by inhibiting the activity of monoamine oxidase, thus preventing the breakdown of monoamine neurotransmitters and thereby increasing their availability. There are two isoforms of monoamine oxidase, MAO-A and MAO-B. MAO-A preferentially deaminates serotonin, melatonin, epinephrine and norepinephrine. MAO-B preferentially deaminates phenylethylamine and trace amines. Pargyline functions by inhibiting the metabolism of catecholamines and tyramine within presynaptic nerve terminals. Catecholamines cause general physiological changes that prepare the body for physical activity (fight-or-flight response). Some typical effects are increases in heart rate, blood pressure, blood glucose levels, and a general reaction of the sympathetic nervous system.

TargetActionsOrganism
AAmine oxidase [flavin-containing] B
inhibitor
Human
UAmine oxidase [flavin-containing] A
inhibitor
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe risk or severity of bleeding and hemorrhage can be increased when Pargyline is combined with (R)-warfarin.
(S)-WarfarinThe risk or severity of bleeding and hemorrhage can be increased when Pargyline is combined with (S)-Warfarin.
2,4-thiazolidinedionePargyline may increase the hypoglycemic activities of 2,4-thiazolidinedione.
2,5-Dimethoxy-4-ethylamphetaminePargyline may increase the hypertensive activities of 2,5-Dimethoxy-4-ethylamphetamine.
2,5-Dimethoxy-4-ethylthioamphetaminePargyline may increase the hypertensive activities of 2,5-Dimethoxy-4-ethylthioamphetamine.
3,4-MethylenedioxyamphetaminePargyline may increase the hypertensive activities of 3,4-Methylenedioxyamphetamine.
4-Bromo-2,5-dimethoxyamphetaminePargyline may increase the hypertensive activities of 4-Bromo-2,5-dimethoxyamphetamine.
4-hydroxycoumarinThe risk or severity of bleeding and hemorrhage can be increased when Pargyline is combined with 4-hydroxycoumarin.
4-MethoxyamphetaminePargyline may increase the hypertensive activities of 4-Methoxyamphetamine.
5-methoxy-N,N-dimethyltryptamineThe metabolism of 5-methoxy-N,N-dimethyltryptamine can be decreased when combined with Pargyline.
Food Interactions
  • Food increases the oral bioavailability by 3-5 fold.

References

General References
Not Available
External Links
Human Metabolome Database
HMDB0015563
KEGG Compound
C07414
PubChem Compound
4688
PubChem Substance
46507368
ChemSpider
4526
BindingDB
50172756
ChEBI
7930
ChEMBL
CHEMBL673
Therapeutic Targets Database
DAP000580
PharmGKB
PA450797
Wikipedia
Pargyline
ATC Codes
C02LL01 — Pargyline and diureticsC02KC01 — Pargyline

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0998 mg/mLALOGPS
logP2.05ALOGPS
logP2.14ChemAxon
logS-3.2ALOGPS
pKa (Strongest Basic)8.13ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area3.24 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity52.18 m3·mol-1ChemAxon
Polarizability18.78 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9504
Blood Brain Barrier+0.9568
Caco-2 permeable+0.8188
P-glycoprotein substrateNon-substrate0.6641
P-glycoprotein inhibitor INon-inhibitor0.9864
P-glycoprotein inhibitor IINon-inhibitor0.9357
Renal organic cation transporterNon-inhibitor0.5518
CYP450 2C9 substrateNon-substrate0.8061
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateNon-substrate0.6977
CYP450 1A2 substrateNon-inhibitor0.7981
CYP450 2C9 inhibitorNon-inhibitor0.9213
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.945
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7826
Ames testNon AMES toxic0.9413
CarcinogenicityNon-carcinogens0.5475
BiodegradationNot ready biodegradable0.9459
Rat acute toxicity2.6935 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.7258
hERG inhibition (predictor II)Non-inhibitor0.8819
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Download (10 KB)
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0006-9200000000-48da979999f0c1f29bef
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0006-9200000000-ab18807e68b6d65f5daf
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0006-9000000000-f966b80b7d4c362bc68c
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0006-9000000000-63358c26586310bea580
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0006-9000000000-a32af1e0d91746768420
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0006-9000000000-dd95e84227d5a66138e1
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-03di-1900000000-23c7df4b4c62d2dce32a
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-0006-9000000000-3b1f68acf7d86b277194
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-0006-9000000000-bc675bae86e11cbc3f46
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-0006-9000000000-6271407e28e1fc55d1a5
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-00kf-9000000000-845489f9fa893fc89498
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0006-9000000000-160af36d11827e420769
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0006-9200000000-90edafcb4957e4893300
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0006-9200000000-1ff0c747d1e83d9eac05
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0006-9000000000-ed7aaa01b064b00e08a7
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0006-9000000000-5ad802258fbfb5471d37

Taxonomy

Description
This compound belongs to the class of organic compounds known as phenylmethylamines. These are compounds containing a phenylmethtylamine moiety, which consists of a phenyl group substituted by an methanamine.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Phenylmethylamines
Direct Parent
Phenylmethylamines
Alternative Parents
Benzylamines / Aralkylamines / Trialkylamines / Acetylides / Organopnictogen compounds / Hydrocarbon derivatives
Substituents
Phenylmethylamine / Benzylamine / Aralkylamine / Tertiary aliphatic amine / Tertiary amine / Acetylide / Organic nitrogen compound / Organopnictogen compound / Hydrocarbon derivative / Organonitrogen compound
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
aromatic amine (CHEBI:7930) / a small molecule (CPD-13898)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
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...
Gene Name
MAOB
Uniprot ID
P27338
Uniprot Name
Amine oxidase [flavin-containing] B
Molecular Weight
58762.475 Da
References
  1. Chrisp P, Mammen GJ, Sorkin EM: Selegiline. A review of its pharmacology, symptomatic benefits and protective potential in Parkinson's disease. Drugs Aging. 1991 May;1(3):228-48. [PubMed:1794016]
  2. Heinonen EH, Myllyla V: Safety of selegiline (deprenyl) in the treatment of Parkinson's disease. Drug Saf. 1998 Jul;19(1):11-22. [PubMed:9673855]
  3. Authors unspecified: Selegiline: a second look. Six years later: too risky in Parkinson's disease. Prescrire Int. 2002 Aug;11(60):108-11. [PubMed:12199263]
  4. Macleod AD, Counsell CE, Ives N, Stowe R: Monoamine oxidase B inhibitors for early Parkinson's disease. Cochrane Database Syst Rev. 2005 Jul 20;(3):CD004898. [PubMed:16034956]
  5. Magyar K, Tothfalusi L: Pharmacokinetic aspects of deprenyl effects. Pol J Pharmacol Pharm. 1984 Jul-Aug;36(4):373-84. [PubMed:6441926]
  6. Heinonen EH, Anttila MI, Lammintausta RA: Pharmacokinetic aspects of l-deprenyl (selegiline) and its metabolites. Clin Pharmacol Ther. 1994 Dec;56(6 Pt 2):742-9. [PubMed:7995016]
  7. Deleu D, Northway MG, Hanssens Y: Clinical pharmacokinetic and pharmacodynamic properties of drugs used in the treatment of Parkinson's disease. Clin Pharmacokinet. 2002;41(4):261-309. [PubMed:11978145]
  8. Patkar AA, Pae CU, Masand PS: Transdermal selegiline: the new generation of monoamine oxidase inhibitors. CNS Spectr. 2006 May;11(5):363-75. [PubMed:16641841]
  9. Azzaro AJ, Ziemniak J, Kemper E, Campbell BJ, VanDenBerg C: Pharmacokinetics and absolute bioavailability of selegiline following treatment of healthy subjects with the selegiline transdermal system (6 mg/24 h): a comparison with oral selegiline capsules. J Clin Pharmacol. 2007 Oct;47(10):1256-67. Epub 2007 Aug 22. [PubMed:17715422]
  10. Lee KC, Chen JJ: Transdermal selegiline for the treatment of major depressive disorder. Neuropsychiatr Dis Treat. 2007;3(5):527-37. [PubMed:19300583]
  11. Baker GB, Sowa B, Todd KG: Amine oxidases and their inhibitors: what can they tell us about neuroprotection and the development of drugs for neuropsychiatric disorders? J Psychiatry Neurosci. 2007 Sep;32(5):313-5. [PubMed:17823646]
  12. Villeneuve C, Caudrillier A, Ordener C, Pizzinat N, Parini A, Mialet-Perez J: Dose-dependent activation of distinct hypertrophic pathways by serotonin in cardiac cells. Am J Physiol Heart Circ Physiol. 2009 Aug;297(2):H821-8. doi: 10.1152/ajpheart.00345.2009. Epub 2009 Jun 19. [PubMed:19542488]
  13. Murphy DL, Karoum F, Pickar D, Cohen RM, Lipper S, Mellow AM, Tariot PN, Sunderland T: Differential trace amine alterations in individuals receiving acetylenic inhibitors of MAO-A (clorgyline) or MAO-B (selegiline and pargyline). J Neural Transm Suppl. 1998;52:39-48. [PubMed:9564606]
  14. Fuentes JA, Ordaz A, Neff NH: Central mediation of the antihypertensive effect of pargyline in spontaneously hypertensive rats. Eur J Pharmacol. 1979 Jul 15;57(1):21-7. [PubMed:477738]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
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...
Gene Name
MAOA
Uniprot ID
P21397
Uniprot Name
Amine oxidase [flavin-containing] A
Molecular Weight
59681.27 Da
References
  1. Patkar AA, Pae CU, Masand PS: Transdermal selegiline: the new generation of monoamine oxidase inhibitors. CNS Spectr. 2006 May;11(5):363-75. [PubMed:16641841]
  2. Azzaro AJ, Ziemniak J, Kemper E, Campbell BJ, VanDenBerg C: Pharmacokinetics and absolute bioavailability of selegiline following treatment of healthy subjects with the selegiline transdermal system (6 mg/24 h): a comparison with oral selegiline capsules. J Clin Pharmacol. 2007 Oct;47(10):1256-67. Epub 2007 Aug 22. [PubMed:17715422]
  3. Lee KC, Chen JJ: Transdermal selegiline for the treatment of major depressive disorder. Neuropsychiatr Dis Treat. 2007;3(5):527-37. [PubMed:19300583]
  4. Baker GB, Sowa B, Todd KG: Amine oxidases and their inhibitors: what can they tell us about neuroprotection and the development of drugs for neuropsychiatric disorders? J Psychiatry Neurosci. 2007 Sep;32(5):313-5. [PubMed:17823646]
  5. Murphy DL, Karoum F, Pickar D, Cohen RM, Lipper S, Mellow AM, Tariot PN, Sunderland T: Differential trace amine alterations in individuals receiving acetylenic inhibitors of MAO-A (clorgyline) or MAO-B (selegiline and pargyline). J Neural Transm Suppl. 1998;52:39-48. [PubMed:9564606]
  6. Fuentes JA, Ordaz A, Neff NH: Central mediation of the antihypertensive effect of pargyline in spontaneously hypertensive rats. Eur J Pharmacol. 1979 Jul 15;57(1):21-7. [PubMed:477738]

Drug created on August 29, 2007 15:04 / Updated on November 02, 2018 08:37