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

Stem definition	Drug id	CAS RN
ergot alkaloid derivatives	888	511-12-6

Description:

Molecule	Description
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

Molecule

Description

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:

Dose	Unit	Route
1	mg	N
4	mg	O
4	mg	P

ADMET properties:

Property	Value	Reference
MRTD (Maximum Recommended Therapeutic Daily Dose)	0.07 µM/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:

Date	Agency	Company	Orphan
April 12, 1946	FDA	VALEANT

FDA Adverse Event Reporting System (Female)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients 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 term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients 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 term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients 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:

Source	Code	Description
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|

Disease	Relation	SNOMED_ID	DOID
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

🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (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 strength	Trade name	Applicant	Application number	Approval date	Type	Dose form	Route	Patent number	Patent expiration date	Patent 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 strength	Trade name	Applicant	Application number	Approval date	Type	Dose form	Route	Exclusivity date	Description
0.725MG/SPRAY	TRUDHESA	IMPEL PHARMS	N213436	Sept. 2, 2021	RX	SPRAY, METERED	NASAL	Sept. 2, 2024	NEW PRODUCT

Bioactivity Summary:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Bioact source	MoA source
5-hydroxytryptamine receptor 1D	GPCR	P28221	5HT1D_HUMAN	AGONIST	Ki	9.90	IUPHAR	CHEMBL
D(1A) dopamine receptor	GPCR	P21728	DRD1_HUMAN		Ki	5.92	DRUG MATRIX
D(2) dopamine receptor	GPCR	P14416	DRD2_HUMAN		Ki	8.53	DRUG MATRIX
Alpha-2A adrenergic receptor	GPCR	P08913	ADA2A_HUMAN		Ki	9.41	DRUG MATRIX
Cytochrome P450 3A4	Enzyme	P08684	CP3A4_HUMAN		IC50	5.30	DRUG MATRIX
5-hydroxytryptamine receptor 1A	GPCR	P08908	5HT1A_HUMAN		Ki	9.42	DRUG MATRIX
5-hydroxytryptamine receptor 2A	GPCR	P28223	5HT2A_HUMAN		Ki	8.64	DRUG MATRIX
5-hydroxytryptamine receptor 2B	GPCR	P41595	5HT2B_HUMAN		Ki	8.36	DRUG MATRIX
5-hydroxytryptamine receptor 2C	GPCR	P28335	5HT2C_HUMAN		Ki	7.33	DRUG MATRIX
5-hydroxytryptamine receptor 6	GPCR	P50406	5HT6R_HUMAN		Ki	8.83	CHEMBL
5-hydroxytryptamine receptor 7	GPCR	P34969	5HT7R_HUMAN	ANTAGONIST	Ki	8	IUPHAR
Alpha-1A adrenergic receptor	GPCR	P35348	ADA1A_HUMAN				WOMBAT-PK
Alpha-2B adrenergic receptor	GPCR	P18089	ADA2B_HUMAN		Ki	8.75	DRUG MATRIX
D(3) dopamine receptor	GPCR	P35462	DRD3_HUMAN		Ki	8.74	DRUG MATRIX
5-hydroxytryptamine receptor 1B	GPCR	P28222	5HT1B_HUMAN	AGONIST	Ki	9.20	IUPHAR
Alpha-2C adrenergic receptor	GPCR	P18825	ADA2C_HUMAN		Ki	8.82	DRUG MATRIX
Alpha-1D adrenergic receptor	GPCR	P25100	ADA1D_HUMAN		Ki	8.69	DRUG MATRIX
Alpha-1B adrenergic receptor	GPCR	P35368	ADA1B_HUMAN				WOMBAT-PK
5-hydroxytryptamine receptor 5A	GPCR	P47898	5HT5A_HUMAN				WOMBAT-PK
5-hydroxytryptamine receptor 1F	GPCR	P30939	5HT1F_HUMAN	AGONIST	Ki	7.10	IUPHAR
5-hydroxytryptamine receptor 1E	GPCR	P28566	5HT1E_HUMAN	AGONIST	Ki	5.60	IUPHAR
Solute carrier family 22 member 2	Transporter	O15244	S22A2_HUMAN		IC50	4.30	CHEMBL
Multidrug and toxin extrusion protein 1	Transporter	Q96FL8	S47A1_HUMAN		IC50	5.55	CHEMBL
Multidrug and toxin extrusion protein 2	Transporter	Q86VL8	S47A2_HUMAN		IC50	4.90	CHEMBL
Alpha-1B adrenergic receptor	GPCR		ADA1B_RAT		Ki	8.35	DRUG MATRIX
5-hydroxytryptamine receptor 1B	GPCR		5HT1B_RAT		Ki	9.42	DRUG MATRIX
Alpha-1A adrenergic receptor	GPCR		ADA1A_RAT		IC50	8.30	CHEMBL
5-hydroxytryptamine receptor 1A	GPCR		5HT1A_RAT		IC50	9.18	CHEMBL
5-hydroxytryptamine receptor 7	GPCR		5HT7R_RAT	ANTAGONIST	Ki	6.80	IUPHAR
Gastrin/cholecystokinin type B receptor	GPCR		GASR_MOUSE		IC50	4.64	CHEMBL
5-hydroxytryptamine receptor 6	GPCR		5HT6R_RAT	ANTAGONIST	Ki	8.30	IUPHAR
5-hydroxytryptamine receptor 4	GPCR		5HT4R_CAVPO		Ki	6.80	DRUG MATRIX
Adrenergic receptor alpha-2	GPCR		ADA2B_RAT ADA2C_RAT ADA2A_RAT		IC50	8.43	CHEMBL

External reference:

ID	Source
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:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
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