papaverine 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | BioActivity |

Stem definitionDrug idCAS RN
spasmolytics with a papaverine-like action 2056 58-74-2

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • papaverine
  • papaverine hydrochloride
  • papaverin
  • papaverine HCl
An alkaloid found in opium but not closely related to the other opium alkaloids in its structure or pharmacological actions. It is a direct-acting smooth muscle relaxant used in the treatment of impotence and as a vasodilator, especially for cerebral vasodilation. The mechanism of its pharmacological actions is not clear, but it apparently can inhibit phosphodiesterases and it may have direct actions on calcium channels.
  • Molecular weight: 339.39
  • Formula: C20H21NO4
  • CLOGP: 3.58
  • LIPINSKI: 0
  • HAC: 5
  • HDO: 0
  • TPSA: 49.81
  • ALOGS: -4.42
  • ROTB: 6

Drug dosage:

DoseUnitRoute
0.10 g O
0.10 g P

ADMET properties:

PropertyValueReference
MRTD (Maximum Recommended Therapeutic Daily Dose) 25.26 µM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 57.20 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution) 1 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 11 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.07 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 1.80 hours Lombardo F, Berellini G, Obach RS
S (Water solubility) 50 mg/mL Bocci G, Oprea TI, Benet LZ
BDDCS (Biopharmaceutical Drug Disposition Classification System) 1 Bocci G, Oprea TI, Benet LZ

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 2.696 High 1
caco2-efflux Caco-2 efflux ratio (BA/AB) 0.521 High 1
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 54.954 10^-6 cm/s High 1
dh-clint Dog hepatocyte intrinsic clearance 48.753 uL/min/10^6 cells High 1
dppb Dog plasma protein binding (% unbound) 11.050 % High 1
fcs-ppb Fetal calf serum protein binding (% unbound) 28.010 % High 1
herg hERG pIC50 4.726 pIC50 High 1
hh-clint Human hepatocyte intrinsic clearance 32.810 uL/min/10^6 cells High 1
hlm-clint Human liver microsomal intrinsic clearance 151.705 uL/min/mg protein High 1
hppb Human plasma protein binding (% unbound) 4.340 % High 1
kinase-safety-class ACVR2A,ACVR2B,AKT3,ALK,AURKA,AXL,BRAF,BTK,CAMK2B,CAMK2D,CDK5,CDK9,CSF1R,DDR1,DYRK1B,EIF2AK3,EPHB4,ERBB2,FLT3,GRK2,ITK,JAK1,JAK2,MAP2K6,MAP3K21,MAP3K7,MAPK10,MAPK7,MAPK9,MAPKAPK2,MARK4,MET,MTOR,NTRK2,PAK4,PDK2,PDK4,PDPK1,PIK3CB,PIK3CD,PIM2,PRKCD,PRKDC,SIK2,SIK3,STK33,SYK,TEK,TTK,ULK1 50
kinase-selectivity-class ACVR2A,ACVR2B,AURKA,AXL,BRAF,DDR1,EIF2AK3,EPHB4,ERBB2,GRK2,IRAK3,JAK1,MAP2K3,MAP3K21,MAPK12,MAPK7,PDK4,PIK3CB,PIK3CD,PRKDC,SIK2,SIK3,TTK 23
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 0.721 High 1
mh-clint Mouse hepatocyte intrinsic clearance 170.608 High 1
mppb Mouse plasma protein binding (% unbound) 9.680 High 1
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 2.070 High 1
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pppb Pig plasma protein binding (% unbound) 20.940 % High 1
rh-clint Rat hepatocyte intrinsic clearance 207.970 uL/min/10^6 cells High 1
rh-fuinc Rat hepatocyte fraction unbound in incubation 73.360 % High 1
rppb Rat plasma protein binding (% unbound) 7.300 % High 1
solubility-dd Solubility at pH 7.4 in DMSO 311.172 uM High 1

Approvals:

DateAgencyCompanyOrphan
None FDA

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Creatinine renal clearance decreased 159.05 64.91 39 1153 18860 90608395
Sedation complication 158.10 64.91 38 1154 16906 90610349
Blood calcium decreased 136.33 64.91 38 1154 30144 90597111
Renal function test abnormal 131.76 64.91 28 1164 7163 90620092
Orthostatic hypotension 124.08 64.91 38 1154 41789 90585466
Creatinine renal clearance increased 121.67 64.91 23 1169 3258 90623997
Drug abuse 120.86 64.91 44 1148 82303 90544952
Sedation 114.68 64.91 37 1155 48134 90579121
Cognitive disorder 105.19 64.91 38 1154 69369 90557886
Depressed level of consciousness 99.73 64.91 37 1155 72747 90554508
Hypotension 90.82 64.91 55 1137 325342 90301913
Balance disorder 89.38 64.91 37 1155 97043 90530212
Multiple drug therapy 87.85 64.91 20 1172 6989 90620266
Toxicity to various agents 75.97 64.91 47 1145 287799 90339456
Constipation 74.54 64.91 46 1146 280349 90346906
Drug interaction 65.03 64.91 42 1150 276411 90350844

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Toxicity to various agents 350.71 73.78 129 532 229007 42391667
Drug abuse 183.35 73.78 66 595 104705 42515969

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Toxicity to various agents 312.56 53.98 154 1722 480401 110107022
Drug abuse 277.43 53.98 106 1770 177305 110410118
Creatinine renal clearance decreased 143.42 53.98 39 1837 21776 110565647
Sedation complication 142.30 53.98 38 1838 19817 110567606
Blood calcium decreased 120.12 53.98 38 1838 35807 110551616
Renal function test abnormal 118.46 53.98 28 1848 8918 110578505
Creatinine renal clearance increased 113.46 53.98 23 1853 3602 110583821
Depressed level of consciousness 112.63 53.98 49 1827 112229 110475194
Overdose 99.65 53.98 57 1819 233737 110353686
Orthostatic hypotension 97.28 53.98 38 1838 66211 110521212
Sedation 91.94 53.98 37 1839 69646 110517777
Drug interaction 89.38 53.98 71 1805 500112 110087311
Cognitive disorder 87.06 53.98 38 1838 87473 110499950
Multiple drug therapy 80.07 53.98 20 1856 7994 110579429
Balance disorder 79.64 53.98 39 1837 116521 110470902
Hypotension 66.13 53.98 61 1815 523788 110063635
Alcohol interaction 56.46 53.98 13 1863 3681 110583742
Constipation 55.73 53.98 47 1829 357739 110229684

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC A03AD01 ALIMENTARY TRACT AND METABOLISM
DRUGS FOR FUNCTIONAL GASTROINTESTINAL DISORDERS
DRUGS FOR FUNCTIONAL GASTROINTESTINAL DISORDERS
Papaverine and derivatives
ATC G04BE02 GENITO URINARY SYSTEM AND SEX HORMONES
UROLOGICALS
UROLOGICALS
Drugs used in erectile dysfunction
ATC G04BE52 GENITO URINARY SYSTEM AND SEX HORMONES
UROLOGICALS
UROLOGICALS
Drugs used in erectile dysfunction
MeSH PA D002317 Cardiovascular Agents
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D010726 Phosphodiesterase Inhibitors
MeSH PA D014665 Vasodilator Agents
MeSH PA D064804 Urological Agents
CHEBI has role CHEBI:35610 antineoplastic agent
CHEBI has role CHEBI:35620 vasodilator agent
CHEBI has role CHEBI:53784 antispasmodic drug
CHEBI has role CHEBI:55323 antidiarrhoeal drug

Related Drugs by ATC class:

A03AD Papaverine and derivatives 2 drugs
drotaverinemoxaverine
G04BE Drugs used in erectile dysfunction 9 drugs
alprostadilapomorphineavanafilmoxisylytesildenafiltadalafiludenafilvardenafilyohimbine

Drug Use | Suggest Off label Use Form| |View source of the data|

DiseaseRelationSNOMED_IDDOID
Cerebral ischemia indication 287731003
Peripheral vascular disease indication 400047006
Sinus tachycardia contraindication 11092001
Myocardial infarction contraindication 22298006 DOID:5844
Glaucoma contraindication 23986001 DOID:1686
Complete atrioventricular block contraindication 27885002
Conduction disorder of the heart contraindication 44808001
Low blood pressure contraindication 45007003
Angina pectoris contraindication 194828000
Disease of liver contraindication 235856003 DOID:409
Chronic myocardial ischemia contraindication 413844008 DOID:3393
Disorder of coronary artery contraindication 414024009
Cardiac Conduction Delay contraindication




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 6.36 Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])		Mechanism
action		Bioact sourceMoA source
Potassium voltage-gated channel subfamily H member 2 Ion channel IC50 5.14 CHEMBL
cGMP-inhibited 3',5'-cyclic phosphodiesterase A Enzyme Ki 6.55 CHEMBL
cAMP-specific 3',5'-cyclic phosphodiesterase 4B Enzyme WOMBAT-PK
Acetylcholinesterase Enzyme IC50 4.61 CHEMBL
cGMP-specific 3',5'-cyclic phosphodiesterase Enzyme IC50 5.06 CHEMBL
cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A Enzyme IC50 7.77 CHEMBL
Cytochrome P450 2C19 Enzyme IC50 6.12 DRUG MATRIX
cAMP-specific 3',5'-cyclic phosphodiesterase 4A Enzyme IC50 6.09 DRUG MATRIX
cAMP-specific 3',5'-cyclic phosphodiesterase 4D Enzyme IC50 5.85 CHEMBL
cGMP-dependent 3',5'-cyclic phosphodiesterase Enzyme IC50 5.64 CHEMBL
cGMP-inhibited 3',5'-cyclic phosphodiesterase B Enzyme Ki 6.38 CHEMBL
Protein-arginine deiminase type-4 Enzyme IC50 4.41 CHEMBL
Phosphodiesterase 1 Enzyme IC50 5.05 CHEMBL
Serine hydroxymethyltransferase, mitochondrial Enzyme IC50 5.57 CHEMBL
Acetylcholinesterase Enzyme IC50 4.61 CHEMBL
Cyclic nucleotide phosphodiesterase PDE3A Enzyme IC50 6.21 CHEMBL
Cyclic AMP-specific phosphodiesterase SSPDE4A1A Enzyme IC50 5.77 CHEMBL
cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A Enzyme IC50 7.44 CHEMBL
Phosphodiesterase 1 Enzyme IC50 5.06 CHEMBL
Phosphodiesterase 1 Enzyme IC50 4.92 CHEMBL

External reference:

IDSource
4019875 VUID
N0000147960 NUI
D02218 KEGG_DRUG
61-25-6 SECONDARY_CAS_RN
4017430 VANDF
4019875 VANDF
C0030350 UMLSCUI
EV1 PDB_CHEM_ID
CHEMBL19224 ChEMBL_ID
DB01113 DRUGBANK_ID
CHEMBL98123 ChEMBL_ID
D010208 MESH_DESCRIPTOR_UI
4680 PUBCHEM_CID
13147 IUPHAR_LIGAND_ID
DAA13NKG2Q UNII
203132 RXNORM
4553 MMSL
5230 MMSL
d00695 MMSL
000694 NDDF
004522 NDDF
372784001 SNOMEDCT_US
40404004 SNOMEDCT_US
58467001 SNOMEDCT_US
DAA13NKG2Q INXIGHT DRUGS

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Papaverine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0517-4002 INJECTION, SOLUTION 30 mg INTRAVENOUS unapproved drug other 16 sections
Papaverine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 14789-121 INJECTION 30 mg INTRAVENOUS unapproved drug other 16 sections
PAPAVERINE HYDROCHLORIDE HUMAN PRESCRIPTION DRUG LABEL 1 54288-142 INJECTION, SOLUTION 30 mg PARENTERAL unapproved drug other 16 sections
Papaverine Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 72516-024 INJECTION, SOLUTION 30 mg INTRAVENOUS unapproved drug other 16 sections