dihydroergotamine ๐Ÿถ Veterinary Use | 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: 4.76
  • 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 ยตM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BDDCS (Biopharmaceutical Drug Disposition Classification System) 2 Bocci G, Oprea TI, 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
S (Water solubility) 0.07 mg/mL Bocci G, Oprea TI, Benet LZ

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
Neovascularisation 219.26 30.60 36 1646 1109 63486231
Paradoxical drug reaction 172.97 30.60 36 1646 4116 63483224
Extrapyramidal disorder 140.69 30.60 38 1644 13246 63474094
Anuria 133.36 30.60 36 1646 12515 63474825
Drug ineffective for unapproved indication 105.45 30.60 38 1644 34025 63453315
Reversible cerebral vasoconstriction syndrome 76.43 30.60 17 1665 2641 63484699
Dyspepsia 60.19 30.60 36 1646 102160 63385180
Ergot poisoning 56.05 30.60 8 1674 93 63487247
Treatment failure 55.07 30.60 44 1638 198999 63288341
Migraine 35.42 30.60 26 1656 103320 63384020
Prinzmetal angina 33.96 30.60 7 1675 757 63486583
Weight decreased 33.81 30.60 39 1643 276759 63210581
Nausea 33.51 30.60 71 1611 854400 62632940
Abdominal pain 31.96 30.60 39 1643 293417 63193923
Posterior reversible encephalopathy syndrome 30.96 30.60 13 1669 17332 63470008
Cerebral vasoconstriction 30.76 30.60 7 1675 1201 63486139

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
Nightmare 339.41 221.80 73 590 14318 34941950
Sedation 311.91 221.80 73 590 20933 34935335
Nephrolithiasis 290.22 221.80 74 589 30259 34926009
Hyperhidrosis 223.31 221.80 74 589 75618 34880650

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
Neovascularisation 216.05 38.74 36 2084 1209 79741059
Nightmare 214.17 38.74 61 2059 25800 79716468
Nephrolithiasis 182.22 38.74 64 2056 53227 79689041
Sedation 176.19 38.74 62 2058 51833 79690435
Paradoxical drug reaction 153.10 38.74 36 2084 7149 79735119
Product used for unknown indication 135.49 38.74 25 2095 1519 79740749
Extrapyramidal disorder 120.39 38.74 38 2082 22641 79719627
Hyperhidrosis 117.89 38.74 64 2056 151428 79590840
Anuria 114.91 38.74 36 2084 20927 79721341
Drug ineffective for unapproved indication 107.22 38.74 43 2077 51195 79691073
Nausea 105.11 38.74 127 1993 957069 78785199
Drug ineffective 103.75 38.74 134 1986 1080779 78661489
Reversible cerebral vasoconstriction syndrome 73.98 38.74 17 2103 3040 79739228
Treatment failure 63.22 38.74 45 2075 170441 79571827
Migraine 59.76 38.74 34 2086 87459 79654809
Product use in unapproved indication 55.90 38.74 49 2071 250310 79491958
Dyspepsia 55.43 38.74 35 2085 108652 79633616
Ergot poisoning 53.23 38.74 8 2112 135 79742133

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC N02CA01 NERVOUS SYSTEM
ANALGESICS
ANTIMIGRAINE PREPARATIONS
Ergot alkaloids
ATC N02CA51 NERVOUS SYSTEM
ANALGESICS
ANTIMIGRAINE PREPARATIONS
Ergot alkaloids
FDA CS M0007665 Ergotamines
CHEBI has role CHEBI:35941 serotonin agonists
CHEBI has role CHEBI:51065 Dopamine receptor agonist
CHEBI has role CHEBI:66991 sympatholytic drug
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
MeSH PA D014662 Vasoconstrictor Agents
FDA EPC N0000175766 Ergotamine Derivative

Drug Use | Suggest Off label Use Form| |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




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 11.58 acidic
pKa2 12.7 acidic
pKa3 13.43 acidic
pKa4 7.56 Basic

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
0.725MG/SPRAY TRUDHESA IMPEL PHARMS N213436 Sept. 2, 2021 RX SPRAY, METERED NASAL 9919117 March 17, 2033 NASAL ADMINISTRATION OF DIHYDROERGOTAMINE MESYLATE BY METERED SPRAY FOR THE ACUTE TREATMENT OF MIGRAINE WITH OR WITHOUT AURA
0.725MG/SPRAY TRUDHESA IMPEL PHARMS N213436 Sept. 2, 2021 RX SPRAY, METERED NASAL 11185497 Jan. 4, 2039 NASAL ADMINISTRATION OF DIHYDROERGOTAMINE MESYLATE BY METERED SPRAY FOR THE ACUTE TREATMENT OF MIGRAINE WITH OR WITHOUT AURA

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
0.725MG/SPRAY TRUDHESA IMPEL PHARMS N213436 Sept. 2, 2021 RX SPRAY, METERED NASAL Sept. 2, 2024 NEW PRODUCT

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
5-hydroxytryptamine receptor 1D GPCR AGONIST Ki 9.90 IUPHAR CHEMBL
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
5-hydroxytryptamine receptor 6 GPCR Ki 8.83 CHEMBL
5-hydroxytryptamine receptor 7 GPCR ANTAGONIST Ki 8 IUPHAR
Alpha-1A adrenergic receptor GPCR WOMBAT-PK
Alpha-2B adrenergic receptor GPCR Ki 8.75 DRUG MATRIX
D(3) dopamine receptor GPCR Ki 8.74 DRUG MATRIX
5-hydroxytryptamine receptor 1B GPCR AGONIST Ki 9.20 IUPHAR
Alpha-2C adrenergic receptor GPCR Ki 8.82 DRUG MATRIX
Alpha-1D adrenergic receptor GPCR Ki 8.69 DRUG MATRIX
Alpha-1B adrenergic receptor GPCR WOMBAT-PK
5-hydroxytryptamine receptor 5A GPCR WOMBAT-PK
5-hydroxytryptamine receptor 1F GPCR AGONIST Ki 7.10 IUPHAR
5-hydroxytryptamine receptor 1E GPCR AGONIST Ki 5.60 IUPHAR
Solute carrier family 22 member 2 Transporter IC50 4.30 CHEMBL
Multidrug and toxin extrusion protein 1 Transporter IC50 5.55 CHEMBL
Multidrug and toxin extrusion protein 2 Transporter IC50 4.90 CHEMBL
Alpha-1B adrenergic receptor GPCR Ki 8.35 DRUG MATRIX
5-hydroxytryptamine receptor 1B GPCR Ki 9.42 DRUG MATRIX
Alpha-1A adrenergic receptor GPCR IC50 8.30 CHEMBL
5-hydroxytryptamine receptor 1A GPCR IC50 9.18 CHEMBL
5-hydroxytryptamine receptor 7 GPCR ANTAGONIST Ki 6.80 IUPHAR
Gastrin/cholecystokinin type B receptor GPCR IC50 4.64 CHEMBL
5-hydroxytryptamine receptor 6 GPCR ANTAGONIST Ki 8.30 IUPHAR
5-hydroxytryptamine receptor 4 GPCR Ki 6.80 DRUG MATRIX
Adrenergic receptor alpha-2 GPCR IC50 8.43 CHEMBL

External reference:

IDSource
D02211 KEGG_DRUG
5989-77-5 SECONDARY_CAS_RN
6190-39-2 SECONDARY_CAS_RN
203176 RXNORM
4018754 VANDF
4019721 VANDF
C0012291 UMLSCUI
CHEBI:4562 CHEBI
2GM PDB_CHEM_ID
CHEMBL1732 ChEMBL_ID
CHEMBL1200517 ChEMBL_ID
D004087 MESH_DESCRIPTOR_UI
DB00320 DRUGBANK_ID
121 IUPHAR_LIGAND_ID
2022 INN_ID
436O5HM03C UNII
10531 PUBCHEM_CID
4600 MMSL
47279 MMSL
d00211 MMSL
000679 NDDF
004529 NDDF
006588 NDDF
387267005 SNOMEDCT_US
387468003 SNOMEDCT_US
48875009 SNOMEDCT_US

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Dihydroergotamine Mesylate HUMAN PRESCRIPTION DRUG LABEL 1 0143-9151 INJECTION 1 mg INTRAMUSCULAR ANDA 22 sections
Dihydroergotamine Mesylate HUMAN PRESCRIPTION DRUG LABEL 1 0143-9273 INJECTION 1 mg INTRAMUSCULAR ANDA 22 sections
Dihydroergotamine Mesylate HUMAN PRESCRIPTION DRUG LABEL 1 0143-9273 INJECTION 1 mg INTRAMUSCULAR ANDA 22 sections
Migranal HUMAN PRESCRIPTION DRUG LABEL 1 0187-0245 SPRAY 4 mg NASAL NDA 28 sections
Migranal HUMAN PRESCRIPTION DRUG LABEL 1 0187-0245 SPRAY 4 mg NASAL NDA 28 sections
Migranal HUMAN PRESCRIPTION DRUG LABEL 1 0187-0245 SPRAY 4 mg NASAL NDA 28 sections
Dihydroergotamine Mesylate HUMAN PRESCRIPTION DRUG LABEL 1 0574-0850 INJECTION, SOLUTION 1 mg SUBCUTANEOUS ANDA 24 sections
Dihydroergotamine Mesylate HUMAN PRESCRIPTION DRUG LABEL 1 0574-0850 INJECTION, SOLUTION 1 mg SUBCUTANEOUS ANDA 24 sections
Dihydroergotamine Mesylate HUMAN PRESCRIPTION DRUG LABEL 1 24201-463 SPRAY 4 mg NASAL ANDA 28 sections
Dihydroergotamine Mesylate HUMAN PRESCRIPTION DRUG LABEL 1 24201-463 SPRAY 4 mg NASAL ANDA 28 sections
dihydroergotamine mesylate HUMAN PRESCRIPTION DRUG LABEL 1 25021-609 INJECTION, SOLUTION 1 mg INTRAVENOUS ANDA 25 sections
dihydroergotamine mesylate HUMAN PRESCRIPTION DRUG LABEL 1 25021-609 INJECTION, SOLUTION 1 mg INTRAVENOUS ANDA 25 sections
Dihydroergotamine Mesylate HUMAN PRESCRIPTION DRUG LABEL 1 61990-0411 INJECTION, SOLUTION 1 mg INTRAVENOUS ANDA 26 sections
Dihydroergotamine Mesylate HUMAN PRESCRIPTION DRUG LABEL 1 61990-0411 INJECTION, SOLUTION 1 mg INTRAVENOUS ANDA 26 sections
Dihydroergotamine Mesylate HUMAN PRESCRIPTION DRUG LABEL 1 62778-336 INJECTION 1 mg INTRAMUSCULAR ANDA 2 sections
D.H.E. 45 HUMAN PRESCRIPTION DRUG LABEL 1 66490-041 INJECTION, SOLUTION 1 mg INTRAVENOUS NDA 25 sections
D.H.E. 45 HUMAN PRESCRIPTION DRUG LABEL 1 66490-041 INJECTION, SOLUTION 1 mg INTRAVENOUS NDA 25 sections
Dihydroergotamine Mesylate Human Prescription Drug Label 1 68083-466 INJECTION 1 mg INTRAVENOUS ANDA 22 sections
Dihydroergotamine Mesylate HUMAN PRESCRIPTION DRUG LABEL 1 68682-357 SPRAY 4 mg NASAL NDA authorized generic 28 sections
Dihydroergotamine Mesylate HUMAN PRESCRIPTION DRUG LABEL 1 68682-357 SPRAY 4 mg NASAL NDA authorized generic 28 sections
Dihydroergotamine Mesylate HUMAN PRESCRIPTION DRUG LABEL 1 68682-357 SPRAY 4 mg NASAL NDA authorized generic 28 sections
Dihydroergotamine Mesylate Nasal HUMAN PRESCRIPTION DRUG LABEL 1 69097-503 SPRAY, METERED 4 mg NASAL ANDA 19 sections
Dihydroergotamine Mesylate Nasal HUMAN PRESCRIPTION DRUG LABEL 1 69097-503 SPRAY, METERED 4 mg NASAL ANDA 19 sections
Dihydroergotamine Mesylate Nasal HUMAN PRESCRIPTION DRUG LABEL 1 69097-740 SPRAY, METERED 4 mg NASAL ANDA 19 sections
Dihydroergotamine Mesylate Nasal HUMAN PRESCRIPTION DRUG LABEL 1 69097-740 SPRAY, METERED 4 mg NASAL ANDA 19 sections
Dihydroergotamine Mesylate HUMAN PRESCRIPTION DRUG LABEL 1 69238-1606 SPRAY 4 mg NASAL ANDA 22 sections
Dihydroergotamine Mesylate HUMAN PRESCRIPTION DRUG LABEL 1 69238-1606 SPRAY 4 mg NASAL ANDA 22 sections
Dromelate HUMAN PRESCRIPTION DRUG LABEL 1 70529-030 INJECTION, SOLUTION 1 mg SUBCUTANEOUS ANDA 22 sections
Dromelate HUMAN PRESCRIPTION DRUG LABEL 1 70529-030 INJECTION, SOLUTION 1 mg SUBCUTANEOUS ANDA 22 sections
Dihydroergotamine mesylate HUMAN PRESCRIPTION DRUG LABEL 1 72888-096 SPRAY 4 mg NASAL ANDA 15 sections