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Identification
NamePargyline
Accession NumberDB01626
Typesmall molecule
Groupsapproved
Description

A monoamine oxidase inhibitor with antihypertensive properties. [PubChem]

Structure
Thumb
SynonymsNot Available
Salts
Name/CAS Structure Properties
Pargyline hydrochloride
Thumb
  • InChI Key: BCXCABRDBBWWGY-UHFFFAOYSA-N
  • Monoisotopic Mass: 195.08147716
  • Average Mass: 195.689
DBSALT000304
Brand names
NameCompany
EutonylNot Available
Brand mixturesNot Available
CategoriesNot Available
CAS number555-57-7
WeightAverage: 159.2276
Monoisotopic: 159.104799421
Chemical FormulaC11H13N
InChI KeyDPWPWRLQFGFJFI-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
Mass Specshow(10 KB)
Taxonomy
KingdomOrganic Compounds
SuperclassBenzenoids
ClassBenzene and Substituted Derivatives
SubclassNot Available
Direct parentBenzene and Substituted Derivatives
Alternative parentsTertiary Amines; Polyamines
Substituentstertiary amine; polyamine; amine; organonitrogen compound
Classification descriptionThis compound belongs to the benzene and substituted derivatives. These are aromatic compounds containing at least one benzene ring.
Pharmacology
IndicationFor the treatment of moderate to severe hypertension.
PharmacodynamicsPargyline 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 actionMAOIs 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.
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
Metabolism
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityNot Available
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 + 0.9504
Blood Brain Barrier + 0.9568
Caco-2 permeable + 0.8188
P-glycoprotein substrate Non-substrate 0.6641
P-glycoprotein inhibitor I Non-inhibitor 0.9864
P-glycoprotein inhibitor II Non-inhibitor 0.9357
Renal organic cation transporter Non-inhibitor 0.5518
CYP450 2C9 substrate Non-substrate 0.8061
CYP450 2D6 substrate Non-substrate 0.9116
CYP450 3A4 substrate Non-substrate 0.6977
CYP450 1A2 substrate Non-inhibitor 0.7981
CYP450 2C9 substrate Non-inhibitor 0.9213
CYP450 2D6 substrate Non-inhibitor 0.9231
CYP450 2C19 substrate Non-inhibitor 0.9025
CYP450 3A4 substrate Non-inhibitor 0.945
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.7826
Ames test Non AMES toxic 0.9413
Carcinogenicity Non-carcinogens 0.5475
Biodegradation Not ready biodegradable 0.9459
Rat acute toxicity 2.6935 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.7258
hERG inhibition (predictor II) Non-inhibitor 0.8819
Pharmacoeconomics
Manufacturers
  • Abbott laboratories pharmaceutical products div
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
Statesolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
water solubility9.98e-02 g/lALOGPS
logP2.05ALOGPS
logP2.14ChemAxon
logS-3.2ALOGPS
pKa (strongest basic)8.13ChemAxon
physiological charge1ChemAxon
hydrogen acceptor count1ChemAxon
hydrogen donor count0ChemAxon
polar surface area3.24ChemAxon
rotatable bond count3ChemAxon
refractivity52.18ChemAxon
polarizability18.78ChemAxon
number of rings1ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterNoChemAxon
Veber's ruleYesChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis ReferenceNot Available
General ReferenceNot Available
External Links
ResourceLink
KEGG CompoundC07414
PubChem Compound4688
PubChem Substance46507368
ChemSpider4526
BindingDB50172756
Therapeutic Targets DatabaseDAP000580
PharmGKBPA450797
WikipediaPargyline
ATC CodesC02KC01C02LL01
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
EpinephrineIncreased arterial pressure
FenoterolIncreased arterial pressure
GuanethidinePargyline may decrease the effect of guanethidine.
MethotrimeprazinePossible severe adverse reaction with this combination
MilnacipranIncrease serotonin levels. Combination therapy is contraindicated.
OrciprenalineIncreased arterial pressure
PhenylephrineIncreased arterial pressure
PhenylpropanolamineIncreased arterial pressure
PseudoephedrineIncreased arterial pressure
TerbutalineIncreased arterial pressure
Food Interactions
  • Food increases the oral bioavailability by 3-5 fold.

Targets

1. Amine oxidase [flavin-containing] B

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Amine oxidase [flavin-containing] B P27338 Details

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
  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
  3. Selegiline: a second look. Six years later: too risky in Parkinson’s disease. Prescrire Int. 2002 Aug;11(60):108-11. Pubmed
  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# Magyar K, Tothfalusi L: Pharmacokinetic aspects of deprenyl effects. Pol J Pharmacol Pharm. 1984 Jul-Aug;36(4):373-84. Pubmed
  5. 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
  6. 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
  7. Patkar AA, Pae CU, Masand PS: Transdermal selegiline: the new generation of monoamine oxidase inhibitors. CNS Spectr. 2006 May;11(5):363-75. Pubmed
  8. 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
  9. Lee KC, Chen JJ: Transdermal selegiline for the treatment of major depressive disorder. Neuropsychiatr Dis Treat. 2007;3(5):527-37. Pubmed
  10. 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
  11. 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. Epub 2009 Jun 19. Pubmed
  12. 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
  13. 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

2. Amine oxidase [flavin-containing] A

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Amine oxidase [flavin-containing] A P21397 Details

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
  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
  3. Lee KC, Chen JJ: Transdermal selegiline for the treatment of major depressive disorder. Neuropsychiatr Dis Treat. 2007;3(5):527-37. Pubmed
  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
  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
  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

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Drug created on August 29, 2007 15:04 / Updated on September 16, 2013 17:15