dihydroergotamine Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definitionDrug idCAS RN
ergot alkaloid derivatives 888 511-12-6

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • dihydroergotamine mesilate
  • dihydroergotamine tartrate
  • dihydroergotamine
  • 9,10-Dihydroergotamine
  • dihydroergotamine mesylate
A 9,10alpha-dihydro derivative of ERGOTAMINE. It is used as a vasoconstrictor, specifically for the therapy of MIGRAINE DISORDERS.
  • Molecular weight: 583.69
  • Formula: C33H37N5O5
  • CLOGP: 4.77
  • LIPINSKI: 1
  • HAC: 10
  • HDO: 3
  • TPSA: 118.21
  • ALOGS: -3.41
  • ROTB: 4

  • Status: OFP

  • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
1 mg N
4 mg O
4 mg P

ADMET properties:

PropertyValueReference
MRTD (Maximum Recommended Therapeutic Daily Dose) 0.07 ┬ÁM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BDDCS (Biopharmaceutical Drug Disposition Classification System) 1 Hosey CM, Chan R, Benet LZ
BA (Bioavailability) 1 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution) 0.33 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 15.07 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) 0.55 hours Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
April 12, 1946 FDA VALEANT

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
Reversible cerebral vasoconstriction syndrome 43.59 36.77 6 90 278 2357711

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

Pharmacologic Action:

SourceCodeDescription
ATC N02CA01 NERVOUS SYSTEM
ANALGESICS
ANTIMIGRAINE PREPARATIONS
Ergot alkaloids
ATC N02CA51 NERVOUS SYSTEM
ANALGESICS
ANTIMIGRAINE PREPARATIONS
Ergot alkaloids
FDA EPC N0000175766 Ergotamine Derivative
FDA Chemical/Ingredient N0000007621 Ergotamines
MeSH PA D000700 Analgesics
MeSH PA D018712 Analgesics, Non-Narcotic
MeSH PA D002317 Cardiovascular Agents
MeSH PA D002491 Central Nervous System Agents
MeSH PA D015259 Dopamine Agents
MeSH PA D018491 Dopamine Agonists
MeSH PA D018377 Neurotransmitter Agents
MeSH PA D018373 Peripheral Nervous System Agents
MeSH PA D018689 Sensory System Agents
CHEBI has role CHEBI:35941 serotonergic agonist
CHEBI has role CHEBI:35481 non-narcotic analgesic
CHEBI has role CHEBI:50514 vasoconstrictor agent
CHEBI has role CHEBI:51065 dopamine agonist
CHEBI has role CHEBI:66991 sympatholytic agent
MeSH PA D014662 Vasoconstrictor Agents

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Migraine indication 37796009 DOID:6364
Vascular headache indication 128187005
Cluster headache syndrome indication 193031009
Bacterial septicemia contraindication 10001005 DOID:0040085
Vascular surgery procedure contraindication 30904006
Hypertensive disorder contraindication 38341003 DOID:10763
Acute nephropathy contraindication 58574008
Hepatic failure contraindication 59927004
Prinzmetal angina contraindication 87343002
Pregnancy, function contraindication 289908002
Cardiovascular event risk contraindication 395112001
Peripheral vascular disease contraindication 400047006
Breastfeeding (mother) contraindication 413712001
Disorder of coronary artery contraindication 414024009
Porphyria contraindication 418470004
Hypertensive urgency contraindication 443482000

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 11.58 acidic
pKa2 12.7 acidic
pKa3 13.43 acidic
pKa4 7.56 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
5-hydroxytryptamine receptor 1D GPCR AGONIST Ki 9.90 IUPHAR CHEMBL
5-hydroxytryptamine receptor 1B GPCR AGONIST Ki 9.20 IUPHAR
5-hydroxytryptamine receptor 1F GPCR AGONIST Ki 7.10 IUPHAR
5-hydroxytryptamine receptor 7 GPCR ANTAGONIST Ki 8 IUPHAR
5-hydroxytryptamine receptor 1E GPCR AGONIST Ki 5.60 IUPHAR
D(1A) dopamine receptor GPCR Ki 5.92 DRUG MATRIX
D(2) dopamine receptor GPCR Ki 8.53 DRUG MATRIX
Alpha-2A adrenergic receptor GPCR Ki 9.41 DRUG MATRIX
Cytochrome P450 3A4 Enzyme IC50 5.30 DRUG MATRIX
5-hydroxytryptamine receptor 1A GPCR Ki 9.42 DRUG MATRIX
5-hydroxytryptamine receptor 2A GPCR Ki 8.64 DRUG MATRIX
5-hydroxytryptamine receptor 2B GPCR Ki 8.36 DRUG MATRIX
5-hydroxytryptamine receptor 2C GPCR Ki 7.33 DRUG MATRIX
Alpha-2B adrenergic receptor GPCR Ki 8.75 DRUG MATRIX
D(3) dopamine receptor GPCR Ki 8.74 DRUG MATRIX
Alpha-2C adrenergic receptor GPCR Ki 8.82 DRUG MATRIX
Alpha-1D adrenergic receptor GPCR Ki 8.69 DRUG MATRIX
5-hydroxytryptamine receptor 5A GPCR WOMBAT-PK
Alpha-1B adrenergic receptor GPCR WOMBAT-PK
Alpha-1A adrenergic receptor GPCR WOMBAT-PK
Solute carrier family 22 member 2 Transporter IC50 4.30 CHEMBL
Multidrug and toxin extrusion protein 2 Transporter IC50 4.90 CHEMBL
Multidrug and toxin extrusion protein 1 Transporter IC50 5.55 CHEMBL
5-hydroxytryptamine receptor 4 GPCR Ki 6.80 DRUG MATRIX
Alpha-1B adrenergic receptor GPCR Ki 8.35 DRUG MATRIX
5-hydroxytryptamine receptor 1B GPCR Ki 9.42 DRUG MATRIX
Adrenergic receptor alpha-2 GPCR IC50 8.43 CHEMBL
Gastrin/cholecystokinin type B receptor GPCR IC50 4.64 CHEMBL
5-hydroxytryptamine receptor 1A GPCR IC50 9.18 CHEMBL
Alpha-1A adrenergic receptor GPCR IC50 8.30 CHEMBL
5-hydroxytryptamine receptor 6 GPCR ANTAGONIST Ki 8.30 IUPHAR
5-hydroxytryptamine receptor 7 GPCR ANTAGONIST Ki 6.80 IUPHAR

External reference:

IDSource
D004087 MESH_DESCRIPTOR_UI
C0771983 UMLSCUI
D02211 KEGG_DRUG
436O5HM03C UNII
2022 INN_ID
5989-77-5 SECONDARY_CAS_RN
3418 RXNORM
387267005 SNOMEDCT_US
d00211 MMSL
48875009 SNOMEDCT_US
4019721 VANDF
004529 NDDF
DB00320 DRUGBANK_ID
CHEMBL1732 ChEMBL_ID
CHEMBL1200517 ChEMBL_ID
2GM PDB_CHEM_ID
CHEBI:4562 CHEBI
121 IUPHAR_LIGAND_ID
10531 PUBCHEM_CID

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Dihydroergotamine Mesylate HUMAN PRESCRIPTION DRUG LABEL 1 0143-9273 INJECTION 1 mg INTRAMUSCULAR ANDA 14 sections
Migranal HUMAN PRESCRIPTION DRUG LABEL 1 0187-0245 SPRAY 4 mg NASAL NDA 16 sections
Dihydroergotamine Mesylate HUMAN PRESCRIPTION DRUG LABEL 1 0574-0850 INJECTION, SOLUTION 1 mg SUBCUTANEOUS ANDA 14 sections
Dihydroergotamine Mesylate HUMAN PRESCRIPTION DRUG LABEL 1 24201-463 SPRAY 4 mg NASAL ANDA 16 sections
dihydroergotamine mesylate HUMAN PRESCRIPTION DRUG LABEL 1 25021-609 INJECTION, SOLUTION 1 mg INTRAVENOUS ANDA 15 sections
Dihydroergotamine Mesylate HUMAN PRESCRIPTION DRUG LABEL 1 61990-0411 INJECTION, SOLUTION 1 mg INTRAVENOUS ANDA 15 sections
D.H.E. 45 HUMAN PRESCRIPTION DRUG LABEL 1 66490-041 INJECTION, SOLUTION 1 mg INTRAVENOUS NDA 14 sections
Dihydroergotamine Mesylate HUMAN PRESCRIPTION DRUG LABEL 1 68682-357 SPRAY 4 mg NASAL NDA authorized generic 16 sections
Dromelate HUMAN PRESCRIPTION DRUG LABEL 1 70529-030 INJECTION, SOLUTION 1 mg SUBCUTANEOUS ANDA 14 sections