phentolamine ๐Ÿถ Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | BioActivity |

Stem definitionDrug idCAS RN
2142 50-60-2

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • phentolamine
  • fentolamine
  • phentolamine mesylate
  • phentolamine mesilate
  • phentolamine hydrochloride
  • phentolamine HCl
A nonselective alpha-adrenergic antagonist. It is used in the treatment of hypertension and hypertensive emergencies, pheochromocytoma, vasospasm of RAYNAUD DISEASE and frostbite, clonidine withdrawal syndrome, impotence, and peripheral vascular disease.
  • Molecular weight: 281.36
  • Formula: C17H19N3O
  • CLOGP: 3.81
  • LIPINSKI: 0
  • HAC: 4
  • HDO: 2
  • TPSA: 47.86
  • ALOGS: -3.02
  • ROTB: 4
  • Status: OFP
    • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
10 mg O
10 mg P

ADMET properties:

PropertyValueReference
MRTD (Maximum Recommended Therapeutic Daily Dose) 15.23 ยตM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BDDCS (Biopharmaceutical Drug Disposition Classification System) 1 Hosey CM, Chan R, Benet LZ
CL (Clearance) 42 mL/min/kg Lombardo F, Berellini G, Obach RS
t_half (Half-life) 2.50 hours Lombardo F, Berellini G, Obach RS
S (Water solubility) 50 mg/mL Bocci G, Oprea TI, Benet LZ
BA (Bioavailability) 0 %

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 0.977 High 1
caco2-efflux Caco-2 efflux ratio (BA/AB) 2.891 High 1
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 7.907 10^-6 cm/s High 1
dh-clint Dog hepatocyte intrinsic clearance 30.200 uL/min/10^6 cells High 1
dppb Dog plasma protein binding (% unbound) 37.820 % High 1
fcs-ppb Fetal calf serum protein binding (% unbound) 52.300 % High 1
herg hERG pIC50 5.658 pIC50 High 1
hh-clint Human hepatocyte intrinsic clearance 15.922 uL/min/10^6 cells High 1
hlm-clint Human liver microsomal intrinsic clearance 37.584 uL/min/mg protein High 1
hppb Human plasma protein binding (% unbound) 41.560 % High 1
kinase-safety-class ACVR2A,ACVR2B,AKT2,AKT3,AURKA,AXL,BRAF,BTK,CAMK2B,CAMK2D,CDK5,CDK9,DDR1,DYRK1B,EIF2AK3,EPHB4,ERBB2,FLT3,GRK2,GSK3B,ITK,JAK2,MAP3K1,MAP3K21,MAP3K7,MAPK10,MAPK7,MAPK9,MAPKAPK2,MARK4,MET,MTOR,NTRK2,PDK2,PDK4,PDPK1,PIK3CB,PIK3CD,PIK3CG,PIM2,PRKCD,PRKDC,SIK2,SIK3,STK33,TEK,TTK 47
kinase-selectivity-class ACVR2A,ACVR2B,AXL,DDR1,EPHB4,ERBB2,GRK2,PDK4,SIK2,SIK3,STK33 11
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 3.864 High 1
mh-clint Mouse hepatocyte intrinsic clearance 205.589 High 1
mppb Mouse plasma protein binding (% unbound) 40.890 High 1
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 11.508 High 1
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pppb Pig plasma protein binding (% unbound) 59.720 % High 1
rh-clint Rat hepatocyte intrinsic clearance 128.233 uL/min/10^6 cells High 1
rh-fuinc Rat hepatocyte fraction unbound in incubation 75.550 % High 1
rppb Rat plasma protein binding (% unbound) 46.950 % High 1
solubility-dd Solubility at pH 7.4 in DMSO 792.501 uM High 1

Approvals:

DateAgencyCompanyOrphan
Jan. 30, 1952 FDA NOVARTIS

FDA Adverse Event Reporting System (Female)

None

FDA Adverse Event Reporting System (Male)

None

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
Neutrophil count increased 59.08 56.75 15 338 34637 110554309

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC C04AB01 CARDIOVASCULAR SYSTEM
PERIPHERAL VASODILATORS
PERIPHERAL VASODILATORS
Imidazoline derivatives
ATC V03AB36 VARIOUS
ALL OTHER THERAPEUTIC PRODUCTS
ALL OTHER THERAPEUTIC PRODUCTS
Antidotes
FDA MoA N0000000099 Adrenergic alpha-Antagonists
FDA EPC N0000175553 alpha-Adrenergic Blocker
MeSH PA D000317 Adrenergic alpha-Antagonists
MeSH PA D000959 Antihypertensive Agents
MeSH PA D002317 Cardiovascular Agents
MeSH PA D018377 Neurotransmitter Agents
MeSH PA D018663 Adrenergic Agents
MeSH PA D018674 Adrenergic Antagonists
CHEBI has role CHEBI:35554 cardiovascular drug
CHEBI has role CHEBI:35620 vasodilator agent
CHEBI has role CHEBI:37890 ฮฑ-adrenergic antagonist
CHEBI has role CHEBI:66981 ophthalmology drug
CHEBI has role CHEBI:74518 anti-obesity agent
CHEBI has role CHEBI:76916 hyperglycemic agent
CHEBI has role CHEBI:35610 antineoplastic agent

Related Drugs by ATC class:

C04AB Imidazoline derivatives 1 drug
tolazoline
V03AB Antidotes 28 drugs
4-dimethylaminophenolacetylcysteineamyl nitriteandexanet alfaatropinecopper sulfatedimercaprolethanolflumazenilfomepizoleglutathionehydroxocobalamin show all 28 →

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

DiseaseRelationSNOMED_IDDOID
Paroxysmal hypertension indication 23130000
Cerebral ischemia indication 287731003
Pheochromocytoma indication 302835009
Peripheral vascular disease indication 400047006
Reverse Mydriasis from Ophthalmic Adrenergic or Anticholinergic Agent indication
Hypertensive Emergencies indication
Diagnostic Test for Pheochromocytoma indication
Dermal Necrosis indication
Hypertension Secondary to Pheochromocytoma indication
Prevention of Hypertension in Pheochromocytoma indication
Extravasation injury off-label use 371100002
Impotence off-label use 397803000
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




๐Ÿถ Veterinary Drug Use

None

๐Ÿถ Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 9.33 acidic
pKa2 7.33 Basic
pKa3 5.88 Basic

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
EQ 0.75% BASE RYZUMVI FAMYGEN LIFE SCI N217064 Sept. 25, 2023 RX SOLUTION OPHTHALMIC 11400077 Oct. 25, 2039 TREATMENT OF PHARMACOLOGICALLY-INDUCED MYDRIASIS
EQ 0.75% BASE RYZUMVI FAMYGEN LIFE SCI N217064 Sept. 25, 2023 RX SOLUTION OPHTHALMIC 12201615 Oct. 25, 2039 TREATMENT OF PHARMACOLOGICALLY-INDUCED MYDRIASIS
EQ 0.75% BASE RYZUMVI FAMYGEN LIFE SCI N217064 Sept. 25, 2023 RX SOLUTION OPHTHALMIC 12201616 Oct. 25, 2039 TREATMENT OF PHARMACOLOGICALLY-INDUCED MYDRIASIS
EQ 0.75% BASE RYZUMVI FAMYGEN LIFE SCI N217064 Sept. 25, 2023 RX SOLUTION OPHTHALMIC 12576066 Oct. 25, 2039 TREATMENT OF PHARMACOLOGICALLY-INDUCED MYDRIASIS
EQ 0.75% BASE RYZUMVI FAMYGEN LIFE SCI N217064 Sept. 25, 2023 RX SOLUTION OPHTHALMIC 12576067 Oct. 25, 2039 TREATMENT OF PHARMACOLOGICALLY-INDUCED MYDRIASIS

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
EQ 0.75% BASE RYZUMVI FAMYGEN LIFE SCI N217064 Sept. 25, 2023 RX SOLUTION OPHTHALMIC Sept. 25, 2026 NEW PRODUCT

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])		Mechanism
action		Bioact sourceMoA source
Alpha-2A adrenergic receptor GPCR ANTAGONIST Ki 8.77 CHEMBL CHEMBL
Alpha-1A adrenergic receptor GPCR ANTAGONIST Ki 8.39 CHEMBL CHEMBL
Alpha-2B adrenergic receptor GPCR ANTAGONIST Ki 8.12 CHEMBL CHEMBL
Alpha-2C adrenergic receptor GPCR ANTAGONIST Ki 8.08 CHEMBL CHEMBL
Alpha-1D adrenergic receptor GPCR ANTAGONIST Ki 7.71 CHEMBL CHEMBL
Alpha-1B adrenergic receptor GPCR ANTAGONIST Ki 7.32 CHEMBL CHEMBL
5-hydroxytryptamine receptor 2C GPCR Ki 6.68 DRUG MATRIX
Histamine H1 receptor GPCR Ki 5.40 PDSP
Cytochrome P450 2D6 Enzyme IC50 5 DRUG MATRIX
Sodium channel alpha subunits; brain (Types I, II, III) Ion channel IC50 5.08 CHEMBL
Nischarin Membrane receptor Ki 7.94 CHEMBL
Sigma non-opioid intracellular receptor 1 Membrane receptor IC50 6.26 CHEMBL
Potassium voltage-gated channel subfamily H member 2 Ion channel Ki 4.78 DRUG MATRIX
5-hydroxytryptamine receptor 1A GPCR Ki 5.67 PDSP
5-hydroxytryptamine receptor 2A GPCR Ki 5.61 PDSP
5-hydroxytryptamine receptor 2B GPCR Ki 5.62 DRUG MATRIX
Histamine H1 receptor GPCR IC50 4.90 CHEMBL
Alpha-2A adrenergic receptor GPCR Ki 9.03 CHEMBL
Alpha-1B adrenergic receptor GPCR Ki 6.66 CHEMBL
Adrenergic receptor alpha-2 GPCR Ki 8.85 CHEMBL
Alpha-1B adrenergic receptor GPCR Ki 7.35 DRUG MATRIX
Alpha-1A adrenergic receptor GPCR IC50 7.96 CHEMBL
Alpha-1D adrenergic receptor GPCR Ki 7.35 CHEMBL
Alpha-2A adrenergic receptor GPCR Ki 8.33 CHEMBL
Alpha-1A adrenergic receptor GPCR Ki 8.17 CHEMBL

External reference:

IDSource
4019892 VUID
N0000147977 NUI
D00509 KEGG_DRUG
65-28-1 SECONDARY_CAS_RN
4018791 VANDF
4019892 VANDF
C0031448 UMLSCUI
CHEBI:8081 CHEBI
CHEMBL597 ChEMBL_ID
DB00692 DRUGBANK_ID
CHEMBL1200873 ChEMBL_ID
D010646 MESH_DESCRIPTOR_UI
5775 PUBCHEM_CID
502 IUPHAR_LIGAND_ID
22 INN_ID
Z468598HBV UNII
227240 RXNORM
11705 MMSL
5280 MMSL
d00733 MMSL
001845 NDDF
001846 NDDF
001847 NDDF
32436002 SNOMEDCT_US
372863003 SNOMEDCT_US
82165003 SNOMEDCT_US
CHEMBL1204146 ChEMBL_ID
73-05-2 SECONDARY_CAS_RN

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Phentolamine Mesylate HUMAN PRESCRIPTION DRUG LABEL 1 0143-9564 INJECTION, POWDER, FOR SOLUTION 5 mg INTRAMUSCULAR ANDA 18 sections
Oraverse HUMAN PRESCRIPTION DRUG LABEL 1 0362-0101 INJECTION, SOLUTION 0.24 mg SUBMUCOSAL NDA 25 sections
PHENTOLAMINE MESYLATE HUMAN PRESCRIPTION DRUG LABEL 1 68094-101 INJECTION 5 mg INTRAVENOUS ANDA 16 sections
Ryzumvi HUMAN PRESCRIPTION DRUG LABEL 1 83368-075 SOLUTION/ DROPS 10 mg OPHTHALMIC NDA 24 sections