Ergotamine
drugOn this page
Also known as ErgotaminaNSC-95090Diergotamine
Summary
Ergotamine (CHEMBL442) is an approved small-molecule non-narcotic analgesic (ATC N02CA72) targeting HTR5A, HTR6, and HTR7; indicated across 2 conditions including migraine disorder and orthostatic hypotension.
At a glance
- Status: Approved (max clinical phase 4)
- Modality: Small molecule
- ATC class: N02CA72 (+2 more)
- Targets: 9 (HTR5A, HTR6, HTR7…)
- Indications: 2 conditions
- Clinical trials: 1
- Chemistry: 581.7 Da · C33H35N5O5
Identifiers
Drug identity and classification
| Field | Value |
|---|---|
| ChEMBL ID | CHEMBL442 |
| Name | Ergotamine |
| Type | Small molecule |
| Max phase | 4 |
| FDA approved | yes |
| PubChem CID | 8223 |
| ChEBI | CHEBI:64318 |
| ATC | N02CA72, N02CA02, N02CA52 |
| Molecular formula | C33H35N5O5 |
| Molecular weight | 581.7 |
| InChIKey | XCGSFFUVFURLIX-VFGNJEKYSA-N |
SMILES: C[C@@]1(C(=O)N2[C@H](C(=O)N3CCC[C@H]3[C@@]2(O1)O)CC4=CC=CC=C4)NC(=O)[C@H]5CN([C@@H]6CC7=CNC8=CC=CC(=C78)C6=C5)C
IUPAC name: (6aR,9R)-N-[(1S,2S,4R,7S)-7-benzyl-2-hydroxy-4-methyl-5,8-dioxo-3-oxa-6,9-diazatricyclo[7.3.0.02,6]dodecan-4-yl]-7-methyl-6,6a,8,9-tetrahydro-4H-indolo[4,3-fg]quinoline-9-carboxamide
ChEBI definition: A peptide ergot alkaloid that is dihydroergotamine in which a double bond replaces the single bond between positions 9 and 10.
Pharmacological roles (ChEBI): non-narcotic analgesic, vasoconstrictor agent, serotonergic agonist, α-adrenergic agonist, mycotoxin, oxytocic.
Also known as: Ergotamina, Ergotamine, NSC-95090, ergotamine, Diergotamine, ERGOTAMINE
Parent form; salt/anhydrous children: CHEMBL2448612
Patent coverage: 5,418 distinct patent families (19,697 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 19,671 (100%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.
Targets
Targets
Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).
| Gene | Target | Action | pAffinity | Cancer dependency | UniProt |
|---|---|---|---|---|---|
| HTR5A | 5-HT5A receptor | Antagonist | 8.7 | 0% | P47898 |
| HTR6 | 5-HT6 receptor | Full agonist | 8.6 | 0.2% | P50406 |
| HTR7 | 5-HT7 receptor | Antagonist | 7.3 | 0.8% | P34969 |
| HTR1D | 5-HT1D receptor | Agonist | 9.1 | 0% | P28221 |
| HTR1E | 5-ht1e receptor | Full agonist | 6.3 | 0% | P28566 |
| HTR1F | 5-HT1F receptor | Full agonist | 6.8 | 0.1% | P30939 |
| HTR2A | 5-HT2A receptor | Partial agonist | 9 | 0% | P28223 |
| HTR2B | 5-HT2B receptor | Partial agonist | 8.9 | 0.4% | P41595 |
| HTR2C | 5-HT2C receptor | Partial agonist | 8.7 | 0% | P28335 |
Broader ChEMBL bioactivity targets: 35 (assay-derived). Sample: 5-hydroxytryptamine receptor 2B, Thromboxane-A synthase, Tyrosine-protein kinase Fyn, Alpha-2A adrenergic receptor, 5-hydroxytryptamine receptor 1B, Alpha-2C adrenergic receptor, Alpha-2B adrenergic receptor, 5-hydroxytryptamine receptor 1D, D(1A) dopamine receptor, Beta-2 adrenergic receptor.
Bioactivity
ChEMBL activities: 66 potent at pChembl ≥ 5 of 74 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):
| Target | pChembl | Type | Value | Unit | Activity ID |
|---|---|---|---|---|---|
| P28564 | 10.04 | Ki | 0.09 | nM | CHEMBL_ACT_7673525 |
| P28564 | 9.7 | IC50 | 0.2 | nM | CHEMBL_ACT_7673524 |
| P19327 | 9.35 | Ki | 0.44 | nM | CHEMBL_ACT_7673523 |
| P19327 | 9.11 | IC50 | 0.77 | nM | CHEMBL_ACT_7673522 |
| HTR1D | 9.1 | Ki | 0.8 | nM | CHEMBL_ACT_433483 |
| ADRA2A | 9.1 | Ki | 0.8 | nM | CHEMBL_ACT_7671330 |
| HTR6 | 9.02 | Ki | 0.95 | nM | CHEMBL_ACT_7673537 |
| DRD2 | 8.84 | Ki | 1.43 | nM | CHEMBL_ACT_7671400 |
| DRD3 | 8.83 | Ki | 1.46 | nM | CHEMBL_ACT_7671402 |
| ADRA2B | 8.76 | Ki | 1.75 | nM | CHEMBL_ACT_7671332 |
| ADRA2C | 8.74 | Ki | 1.81 | nM | CHEMBL_ACT_7671334 |
| HTR2A | 8.73 | Ki | 1.85 | nM | CHEMBL_ACT_7673527 |
| HTR6 | 8.69 | IC50 | 2.04 | nM | CHEMBL_ACT_7673536 |
| HTR1B | 8.68 | Ki | 2.1 | nM | CHEMBL_ACT_7844614 |
| ADRA2A | 8.67 | IC50 | 2.12 | nM | CHEMBL_ACT_7671329 |
| HTR1D | 8.66 | Ki | 2.2 | nM | CHEMBL_ACT_13876538 |
| HTR2B | 8.66 | Ki | 2.2 | nM | CHEMBL_ACT_7673529 |
| HTR1D | 8.58 | Ki | 2.63 | nM | CHEMBL_ACT_13876503 |
| HTR1B | 8.52 | Ki | 3.02 | nM | CHEMBL_ACT_13876504 |
| HTR1B | 8.51 | Ki | 3.1 | nM | CHEMBL_ACT_13876722 |
| P43140 | 8.49 | Ki | 3.26 | nM | CHEMBL_ACT_7669315 |
| HTR2B | 8.46 | IC50 | 3.46 | nM | CHEMBL_ACT_7673528 |
| ADRA2B | 8.41 | IC50 | 3.84 | nM | CHEMBL_ACT_7671331 |
| DRD2 | 8.37 | IC50 | 4.3 | nM | CHEMBL_ACT_7671399 |
| DRD3 | 8.37 | IC50 | 4.31 | nM | CHEMBL_ACT_7671401 |
| HTR1D | 8.37 | Ki | 4.3 | nM | CHEMBL_ACT_7844615 |
| P15823 | 8.34 | Ki | 4.55 | nM | CHEMBL_ACT_7669317 |
| HTR1D | 8.22 | Ki | 6 | nM | CHEMBL_ACT_6356098 |
| HTR2A | 8.19 | IC50 | 6.49 | nM | CHEMBL_ACT_7673526 |
| HTR2A | 8.14 | EC50 | 7.3 | nM | CHEMBL_ACT_25553096 |
Target pathways
Aggregated over 9 target gene(s): HTR5A, HTR6, HTR7, HTR1D, HTR1E, HTR1F, HTR2A, HTR2B, HTR2C.
Top Reactome pathways
11 total, by targets touching each:
| Pathway | Targets | Genes |
|---|---|---|
| Signal Transduction | 9 | HTR1D, HTR1E, HTR1F, HTR2A, HTR2B, HTR2C, HTR5A, HTR6, HTR7 |
| Signaling by GPCR | 9 | HTR1D, HTR1E, HTR1F, HTR2A, HTR2B, HTR2C, HTR5A, HTR6, HTR7 |
| Class A/1 (Rhodopsin-like receptors) | 9 | HTR1D, HTR1E, HTR1F, HTR2A, HTR2B, HTR2C, HTR5A, HTR6, HTR7 |
| Amine ligand-binding receptors | 9 | HTR1D, HTR1E, HTR1F, HTR2A, HTR2B, HTR2C, HTR5A, HTR6, HTR7 |
| GPCR downstream signalling | 9 | HTR1D, HTR1E, HTR1F, HTR2A, HTR2B, HTR2C, HTR5A, HTR6, HTR7 |
| Serotonin receptors | 9 | HTR1D, HTR1E, HTR1F, HTR2A, HTR2B, HTR2C, HTR5A, HTR6, HTR7 |
| GPCR ligand binding | 9 | HTR1D, HTR1E, HTR1F, HTR2A, HTR2B, HTR2C, HTR5A, HTR6, HTR7 |
| G alpha (i) signalling events | 4 | HTR1D, HTR1E, HTR1F, HTR5A |
| G alpha (q) signalling events | 3 | HTR2A, HTR2B, HTR2C |
| G alpha (s) signalling events | 2 | HTR6, HTR7 |
| RHOBTB3 ATPase cycle | 1 | HTR7 |
Dominant GO biological processes
| GO term | Targets |
|---|---|
| G protein-coupled receptor signaling pathway | 9 |
| G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger | 9 |
| chemical synaptic transmission | 9 |
| signal transduction | 9 |
| G protein-coupled serotonin receptor signaling pathway | 6 |
| adenylate cyclase-activating G protein-coupled receptor signaling pathway | 4 |
| adenylate cyclase-inhibiting serotonin receptor signaling pathway | 4 |
| smooth muscle contraction | 3 |
| vasoconstriction | 3 |
| adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway | 3 |
| intracellular calcium ion homeostasis | 3 |
| phospholipase C-activating serotonin receptor signaling pathway | 3 |
| serotonin receptor signaling pathway | 3 |
| positive regulation of phosphatidylinositol biosynthetic process | 3 |
| release of sequestered calcium ion into cytosol | 3 |
Indications & clinical
Indications
2 indications (1 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).
| Indication | Trial phase | MONDO | EFO |
|---|---|---|---|
| migraine disorder | 4 | MONDO:0005277 | MONDO:0005277 |
| orthostatic hypotension | 1 | MONDO:0005469 | EFO:0005252 |
Clinical trials
Total trials: 1.
Phase distribution
| Phase | Trials |
|---|---|
| PHASE1 | 1 |
Top trials by phase / activity
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT00223691 | PHASE1 | COMPLETED | Treatment of Orthostatic Hypotension in Autonomic Failure |
Clinical evidence (CIViC)
No CIViC predictive evidence (expected for non-precision-medicine drugs).
Pharmacology
Pharmacogenomics
No CPIC/DPWG dosing guideline or drug-level clinical/variant annotations in PharmGKB for this molecule.
Related molecules
Related molecules
Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.
598 molecules share ≥1 primary target. Top 60 by shared-target count:
| Molecule | Source | Status | Shared targets |
|---|---|---|---|
| DIHYDROERGOTAMINE | ChEMBL + PubChem | Phase 4 (approved) | HTR1D, HTR1E, HTR1F, HTR2A, HTR2B, HTR2C, HTR5A, HTR6, HTR7 |
| IMIPRAMINE | ChEMBL + PubChem | Phase 4 (approved) | HTR1D, HTR1E, HTR1F, HTR2A, HTR2B, HTR2C, HTR5A, HTR6, HTR7 |
| RISPERIDONE | ChEMBL + PubChem | Phase 4 (approved) | HTR1D, HTR1E, HTR1F, HTR2A, HTR2B, HTR2C, HTR5A, HTR6, HTR7 |
| SEROTONIN | ChEMBL + PubChem | Phase 3 (approved) | HTR1D, HTR1E, HTR1F, HTR2A, HTR2B, HTR2C, HTR5A, HTR6, HTR7 |
| MEBUFOTENIN | ChEMBL | Phase 2 | HTR1D, HTR1E, HTR1F, HTR2A, HTR2B, HTR2C, HTR5A, HTR6, HTR7 |
| BREXPIPRAZOLE | ChEMBL + PubChem | Phase 4 (approved) | HTR1D, HTR1E, HTR2A, HTR2B, HTR2C, HTR5A, HTR6, HTR7 |
| CLOZAPINE | ChEMBL + PubChem | Phase 4 (approved) | HTR1E, HTR1F, HTR2A, HTR2B, HTR2C, HTR5A, HTR6, HTR7 |
| Cyproheptadine | ChEMBL + PubChem | Phase 4 (approved) | HTR1E, HTR1F, HTR2A, HTR2B, HTR2C, HTR5A, HTR6, HTR7 |
| OLANZAPINE | ChEMBL + PubChem | Phase 4 (approved) | HTR1E, HTR1F, HTR2A, HTR2B, HTR2C, HTR5A, HTR6, HTR7 |
| SORAFENIB | ChEMBL + PubChem | Phase 4 (approved) | HTR1E, HTR1F, HTR2A, HTR2B, HTR2C, HTR5A, HTR6, HTR7 |
| SUMATRIPTAN | ChEMBL + PubChem | Phase 4 (approved) | HTR1D, HTR1E, HTR1F, HTR2A, HTR2B, HTR2C, HTR5A, HTR7 |
| LATREPIRDINE | ChEMBL | Phase 3 | HTR1D, HTR1E, HTR2A, HTR2B, HTR2C, HTR5A, HTR6, HTR7 |
| LYSERGIDE | ChEMBL | Phase 2 | HTR1D, HTR1E, HTR2A, HTR2B, HTR2C, HTR5A, HTR6, HTR7 |
| PSILOCIN | ChEMBL | Phase 2 | HTR1D, HTR1E, HTR2A, HTR2B, HTR2C, HTR5A, HTR6, HTR7 |
| QUETIAPINE | ChEMBL + PubChem | Phase 4 (approved) | HTR1E, HTR1F, HTR2A, HTR2B, HTR2C, HTR6, HTR7 |
| TEGASEROD | ChEMBL + PubChem | Phase 4 (approved) | HTR1D, HTR2A, HTR2B, HTR2C, HTR5A, HTR6, HTR7 |
| ARIPIPRAZOLE | ChEMBL | Phase 4 (approved) | HTR1D, HTR2A, HTR2B, HTR2C, HTR5A, HTR6, HTR7 |
| AZELASTINE | ChEMBL | Phase 4 (approved) | HTR1D, HTR1E, HTR2A, HTR2B, HTR2C, HTR6, HTR7 |
| CARIPRAZINE | ChEMBL | Phase 4 (approved) | HTR1D, HTR2A, HTR2B, HTR2C, HTR5A, HTR6, HTR7 |
| CINACALCET | ChEMBL | Phase 4 (approved) | HTR1D, HTR2A, HTR2B, HTR2C, HTR5A, HTR6, HTR7 |
| KETANSERIN | ChEMBL | Phase 4 (approved) | HTR1D, HTR2A, HTR2B, HTR2C, HTR5A, HTR6, HTR7 |
| NEFAZODONE | ChEMBL | Phase 4 (approved) | HTR1D, HTR2A, HTR2B, HTR2C, HTR5A, HTR6, HTR7 |
| PENFLURIDOL | ChEMBL | Phase 2 | HTR1D, HTR2A, HTR2B, HTR2C, HTR5A, HTR6, HTR7 |
| AMOXAPINE | ChEMBL + PubChem | Phase 4 (approved) | HTR2A, HTR2B, HTR2C, HTR5A, HTR6, HTR7 |
| CHLORPROMAZINE | ChEMBL + PubChem | Phase 4 (approved) | HTR2A, HTR2B, HTR2C, HTR5A, HTR6, HTR7 |
| DOXEPIN | ChEMBL + PubChem | Phase 4 (approved) | HTR2A, HTR2B, HTR2C, HTR5A, HTR6, HTR7 |
| HALOPERIDOL | ChEMBL + PubChem | Phase 4 (approved) | HTR2A, HTR2B, HTR2C, HTR5A, HTR6, HTR7 |
| Lasmiditan | ChEMBL + PubChem | Phase 4 (approved) | HTR1D, HTR1E, HTR1F, HTR2B, HTR5A, HTR7 |
| LOXAPINE | ChEMBL + PubChem | Phase 4 (approved) | HTR2A, HTR2B, HTR2C, HTR5A, HTR6, HTR7 |
| METHYLERGONOVINE | ChEMBL + PubChem | Phase 4 (approved) | HTR1E, HTR1F, HTR2A, HTR2B, HTR2C, HTR6 |
| RIZATRIPTAN | ChEMBL + PubChem | Phase 4 (approved) | HTR1D, HTR1E, HTR1F, HTR2A, HTR2B, HTR2C |
| ZIPRASIDONE | ChEMBL + PubChem | Phase 4 (approved) | HTR1E, HTR2A, HTR2B, HTR2C, HTR6, HTR7 |
| ASTEMIZOLE | ChEMBL | Phase 4 (approved) | HTR2A, HTR2B, HTR2C, HTR5A, HTR6, HTR7 |
| MIANSERIN | ChEMBL | Phase 4 (approved) | HTR1D, HTR2A, HTR2B, HTR2C, HTR6, HTR7 |
| PROMAZINE | ChEMBL | Phase 4 (approved) | HTR2A, HTR2B, HTR2C, HTR5A, HTR6, HTR7 |
| YOHIMBINE | ChEMBL + PubChem | Phase 3 (approved) | HTR1D, HTR1E, HTR1F, HTR2A, HTR2B, HTR6 |
| RITANSERIN | ChEMBL | Phase 2 | HTR1E, HTR2A, HTR2C, HTR5A, HTR6, HTR7 |
| SPIPERONE | ChEMBL | Phase 2 | HTR2A, HTR2B, HTR2C, HTR5A, HTR6, HTR7 |
| ASENAPINE | ChEMBL + PubChem | Phase 4 (approved) | HTR1E, HTR2A, HTR2B, HTR2C, HTR6 |
| DIPHENHYDRAMINE | ChEMBL + PubChem | Phase 4 (approved) | HTR2A, HTR2B, HTR2C, HTR5A, HTR6 |
| Fluoxetine | ChEMBL + PubChem | Phase 4 (approved) | HTR2A, HTR2B, HTR2C, HTR5A, HTR6 |
| HYDROXYZINE | ChEMBL + PubChem | Phase 4 (approved) | HTR2A, HTR2B, HTR5A, HTR6, HTR7 |
| Pramipexole | ChEMBL + PubChem | Phase 4 (approved) | HTR1E, HTR2A, HTR2B, HTR5A, HTR7 |
| CARVEDILOL | ChEMBL | Phase 4 (approved) | HTR2A, HTR2B, HTR2C, HTR6, HTR7 |
| FLUPHENAZINE | ChEMBL | Phase 4 (approved) | HTR2A, HTR2B, HTR2C, HTR6, HTR7 |
| IPRINDOLE | ChEMBL | Phase 4 (approved) | HTR2A, HTR2B, HTR2C, HTR5A, HTR6 |
| KETOTIFEN | ChEMBL | Phase 4 (approved) | HTR2A, HTR2B, HTR2C, HTR6, HTR7 |
| METHYSERGIDE | ChEMBL | Phase 4 (approved) | HTR2A, HTR2B, HTR2C, HTR6, HTR7 |
| OXYMETAZOLINE | ChEMBL | Phase 4 (approved) | HTR1D, HTR2A, HTR2B, HTR2C, HTR6 |
| SALMETEROL | ChEMBL | Phase 4 (approved) | HTR1D, HTR2A, HTR2B, HTR2C, HTR7 |
| SUNITINIB | ChEMBL | Phase 4 (approved) | HTR2A, HTR2B, HTR2C, HTR5A, HTR6 |
| THIORIDAZINE | ChEMBL | Phase 4 (approved) | HTR2A, HTR2B, HTR2C, HTR6, HTR7 |
| THIOTHIXENE | ChEMBL | Phase 4 (approved) | HTR2A, HTR2B, HTR2C, HTR6, HTR7 |
| CHLOROPHENYLPIPERAZINE | ChEMBL | Phase 2 | HTR2A, HTR2B, HTR2C, HTR6, HTR7 |
| FANANSERIN | ChEMBL | Phase 2 | HTR2A, HTR2C, HTR5A, HTR6, HTR7 |
| GSK163090 | ChEMBL | Phase 2 | HTR1D, HTR2A, HTR2B, HTR2C, HTR7 |
| MESULERGINE | ChEMBL | Phase 2 | HTR2A, HTR2B, HTR2C, HTR6, HTR7 |
| METERGOLINE | ChEMBL | Phase 2 | HTR2A, HTR2B, HTR2C, HTR6, HTR7 |
| METITEPINE | ChEMBL | Phase 2 | HTR2A, HTR2C, HTR5A, HTR6, HTR7 |
| PRUVANSERIN | ChEMBL | Phase 2 | HTR1D, HTR2A, HTR2B, HTR2C, HTR7 |
Related Atlas pages
- Genes: HTR5A, HTR6, HTR7, HTR1D, HTR1E, HTR1F, HTR2A, HTR2B, HTR2C
- Diseases: migraine disorder
- Drugs: Dihydroergotamine, Imipramine, Risperidone, Serotonin, Brexpiprazole, Clozapine, Cyproheptadine, Olanzapine, Sorafenib, Sumatriptan, Latrepirdine, Quetiapine, Tegaserod, Aripiprazole, Azelastine, Cariprazine, Cinacalcet, Ketanserin, Nefazodone, Amoxapine, Chlorpromazine, Doxepin, Haloperidol, Lasmiditan, Loxapine, Methylergonovine, Rizatriptan, Ziprasidone, Astemizole, Mianserin, Promazine, Yohimbine, Asenapine, Diphenhydramine, Fluoxetine, Hydroxyzine, Pramipexole, Carvedilol, Fluphenazine, Iprindole, Ketotifen, Methysergide, Oxymetazoline, Salmeterol, Sunitinib, Thioridazine, Thiothixene