Methysergide

Summary

Methysergide (CHEMBL1065) is an approved small molecule (ATC N02CA04) targeting HTR5A, HTR6, and HTR7; indicated across 1 condition including migraine disorder.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: N02CA04
• Targets: 10 (HTR5A, HTR6, HTR7…)
• Indications: 1 condition
• Chemistry: 353.5 Da · C21H27N3O2

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL1065
Name	Methysergide
Type	Small molecule
Max phase	4
FDA approved	no
PubChem CID	9681
ATC	N02CA04
Molecular formula	C21H27N3O2
Molecular weight	353.5
InChIKey	KPJZHOPZRAFDTN-ZRGWGRIASA-N

SMILES: CC[C@@H](CO)NC(=O)[C@H]1CN([C@@H]2CC3=CN(C4=CC=CC(=C34)C2=C1)C)C

IUPAC name: (6aR,9R)-N-[(2S)-1-hydroxybutan-2-yl]-4,7-dimethyl-6,6a,8,9-tetrahydroindolo[4,3-fg]quinoline-9-carboxamide

Also known as: Deseril, Methysergide, Metisergida, methysergide, SID26751590, SID90340563, METHYSERGIDE, SID144204446, SID170464684

Parent form; salt/anhydrous children: CHEMBL1200938

Patent coverage: 2,269 distinct patent families (8,455 SureChEMBL compound mentions), from 1 matched compound structure(s). 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	7	0%	P47898
HTR6	5-HT6 receptor	Antagonist	6.8	0.2%	P50406
HTR7	5-HT7 receptor	Antagonist	7.8	0.8%	P34969
HTR1B	5-HT1B receptor	Antagonist	7.6	0.2%	P28222
HTR1D	5-HT1D receptor	Antagonist	8.9	0%	P28221
HTR1E	5-ht1e receptor	Antagonist	6.8	0%	P28566
HTR1F	5-HT1F receptor	Antagonist	8.2	0.1%	P30939
HTR2A	5-HT2A receptor	Antagonist	8.4	0%	P28223
HTR2B	5-HT2B receptor	Partial agonist	9.4	0.4%	P41595
HTR2C	5-HT2C receptor	Antagonist	9.1	0%	P28335

Broader ChEMBL bioactivity targets: 31 (assay-derived). Sample: ATP-dependent DNA helicase Q1, Histone-lysine N-methyltransferase 2A, 5-hydroxytryptamine receptor 2B, Alpha-2A adrenergic receptor, Alpha-2C adrenergic receptor, Histamine H2 receptor, Alpha-2B adrenergic receptor, D(1A) dopamine receptor, Thromboxane A2 receptor, Progesterone receptor.

Bioactivity

ChEMBL activities: 58 potent at pChembl ≥ 5 of 68 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
HTR2B	9.45	Ki	0.36	nM	CHEMBL_ACT_7749630
HTR2B	9.25	IC50	0.56	nM	CHEMBL_ACT_7749629
HTR2C	8.96	Ki	1.09	nM	CHEMBL_ACT_7749632
P14842	8.84	Ki	1.45	nM	CHEMBL_ACT_1204044
P08909	8.84	Ki	1.45	nM	CHEMBL_ACT_1229698
HTR2A	8.8	Ki	1.58	nM	CHEMBL_ACT_12164416
P14842	8.8	Ki	1.6	nM	CHEMBL_ACT_559975
P14842	8.7	Ki	2	nM	CHEMBL_ACT_92656
HTR2C	8.68	IC50	2.09	nM	CHEMBL_ACT_7749631
HTR2C	8.6	Ki	2.5	nM	CHEMBL_ACT_2536483
HTR2B	8.55	AC50	2.8	nM	CHEMBL_ACT_25164300
HTR2A	8.42	Ki	3.83	nM	CHEMBL_ACT_7749628
HTR2B	8.36	AC50	4.4	nM	CHEMBL_ACT_25164234
HTR2B	8.36	AC50	4.4	nM	CHEMBL_ACT_25227965
P08909	8.3	IC50	5.01	nM	CHEMBL_ACT_857047
P08909	8.28	Ki	5.3	nM	CHEMBL_ACT_687547
HTR2B	8.12	Ki	7.59	nM	CHEMBL_ACT_13876499
HTR2B	8.12	Ki	7.6	nM	CHEMBL_ACT_13876534
HTR2A	8.11	AC50	7.7	nM	CHEMBL_ACT_25173766
HTR2C	8.09	AC50	8.2	nM	CHEMBL_ACT_25132257
HTR2A	8	Ki	10	nM	CHEMBL_ACT_2536482
P32305	7.9	Ki	12.59	nM	CHEMBL_ACT_1186870
HTR7	7.9	Ki	12.59	nM	CHEMBL_ACT_196934
HTR2A	7.89	IC50	13	nM	CHEMBL_ACT_7749627
P19327	7.51	Ki	31	nM	CHEMBL_ACT_7749624
P19327	7.5	IC50	31.62	nM	CHEMBL_ACT_857046
P19327	7.27	IC50	54	nM	CHEMBL_ACT_7749623
DRD3	7.23	Ki	59	nM	CHEMBL_ACT_7747487
HTR6	7.12	Ki	75	nM	CHEMBL_ACT_7749638
HTR7	7.1	Ki	79.43	nM	CHEMBL_ACT_18999758

Target pathways

Aggregated over 10 target gene(s): HTR5A, HTR6, HTR7, HTR1B, HTR1D, HTR1E, HTR1F, HTR2A, HTR2B, HTR2C.

Top Reactome pathways

11 total, by targets touching each:

Pathway	Targets	Genes
Signal Transduction	10	HTR1B, HTR1D, HTR1E, HTR1F, HTR2A, HTR2B, HTR2C, HTR5A, HTR6, HTR7
Signaling by GPCR	10	HTR1B, HTR1D, HTR1E, HTR1F, HTR2A, HTR2B, HTR2C, HTR5A, HTR6, HTR7
Class A/1 (Rhodopsin-like receptors)	10	HTR1B, HTR1D, HTR1E, HTR1F, HTR2A, HTR2B, HTR2C, HTR5A, HTR6, HTR7
Amine ligand-binding receptors	10	HTR1B, HTR1D, HTR1E, HTR1F, HTR2A, HTR2B, HTR2C, HTR5A, HTR6, HTR7
GPCR downstream signalling	10	HTR1B, HTR1D, HTR1E, HTR1F, HTR2A, HTR2B, HTR2C, HTR5A, HTR6, HTR7
Serotonin receptors	10	HTR1B, HTR1D, HTR1E, HTR1F, HTR2A, HTR2B, HTR2C, HTR5A, HTR6, HTR7
GPCR ligand binding	10	HTR1B, HTR1D, HTR1E, HTR1F, HTR2A, HTR2B, HTR2C, HTR5A, HTR6, HTR7
G alpha (i) signalling events	5	HTR1B, 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	10
G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger	10
chemical synaptic transmission	10
signal transduction	10
G protein-coupled serotonin receptor signaling pathway	6
adenylate cyclase-inhibiting serotonin receptor signaling pathway	5
adenylate cyclase-activating G protein-coupled receptor signaling pathway	4
vasoconstriction	4
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	4
phospholipase C-activating serotonin receptor signaling pathway	4
smooth muscle contraction	3
regulation of behavior	3
intracellular calcium ion homeostasis	3
serotonin receptor signaling pathway	3
positive regulation of phosphatidylinositol biosynthetic process	3

Indications & clinical

Indications

1 indication (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

Clinical trials

Total trials: 0.

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline, but PharmGKB curates 1 clinical and 1 variant annotation(s) for this drug (gene-keyed; see PharmGKB).

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.

600 molecules share ≥1 primary target. Top 60 by shared-target count:

Molecule	Source	Status	Shared targets
DIHYDROERGOTAMINE	ChEMBL + PubChem	Phase 4 (approved)	HTR1B, HTR1D, HTR1E, HTR1F, HTR2A, HTR2B, HTR2C, HTR5A, HTR6, HTR7
IMIPRAMINE	ChEMBL + PubChem	Phase 4 (approved)	HTR1B, HTR1D, HTR1E, HTR1F, HTR2A, HTR2B, HTR2C, HTR5A, HTR6, HTR7
RISPERIDONE	ChEMBL + PubChem	Phase 4 (approved)	HTR1B, HTR1D, HTR1E, HTR1F, HTR2A, HTR2B, HTR2C, HTR5A, HTR6, HTR7
SEROTONIN	ChEMBL + PubChem	Phase 3 (approved)	HTR1B, HTR1D, HTR1E, HTR1F, HTR2A, HTR2B, HTR2C, HTR5A, HTR6, HTR7
MEBUFOTENIN	ChEMBL	Phase 2	HTR1B, HTR1D, HTR1E, HTR1F, HTR2A, HTR2B, HTR2C, HTR5A, HTR6, HTR7
BREXPIPRAZOLE	ChEMBL + PubChem	Phase 4 (approved)	HTR1B, HTR1D, HTR1E, HTR2A, HTR2B, HTR2C, HTR5A, HTR6, HTR7
CLOZAPINE	ChEMBL + PubChem	Phase 4 (approved)	HTR1B, HTR1E, HTR1F, HTR2A, HTR2B, HTR2C, HTR5A, HTR6, HTR7
ERGOTAMINE	ChEMBL + PubChem	Phase 4 (approved)	HTR1B, HTR1D, HTR1E, HTR1F, HTR2A, HTR2B, HTR2C, HTR5A, HTR6
OLANZAPINE	ChEMBL + PubChem	Phase 4 (approved)	HTR1B, HTR1E, HTR1F, HTR2A, HTR2B, HTR2C, HTR5A, HTR6, HTR7
SUMATRIPTAN	ChEMBL + PubChem	Phase 4 (approved)	HTR1B, HTR1D, HTR1E, HTR1F, HTR2A, HTR2B, HTR2C, HTR5A, HTR7
PSILOCIN	ChEMBL	Phase 2	HTR1B, HTR1D, HTR1E, HTR2A, HTR2B, HTR2C, HTR5A, HTR6, HTR7
Cyproheptadine	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
ARIPIPRAZOLE	ChEMBL	Phase 4 (approved)	HTR1B, HTR1D, HTR2A, HTR2B, HTR2C, HTR5A, HTR6, HTR7
AZELASTINE	ChEMBL	Phase 4 (approved)	HTR1B, HTR1D, HTR1E, HTR2A, HTR2B, HTR2C, HTR6, HTR7
CARIPRAZINE	ChEMBL	Phase 4 (approved)	HTR1B, HTR1D, HTR2A, HTR2B, HTR2C, HTR5A, HTR6, HTR7
KETANSERIN	ChEMBL	Phase 4 (approved)	HTR1B, HTR1D, HTR2A, HTR2B, HTR2C, HTR5A, HTR6, HTR7
NEFAZODONE	ChEMBL	Phase 4 (approved)	HTR1B, HTR1D, HTR2A, HTR2B, HTR2C, HTR5A, HTR6, 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
QUETIAPINE	ChEMBL + PubChem	Phase 4 (approved)	HTR1E, HTR1F, HTR2A, HTR2B, HTR2C, HTR6, HTR7
RIZATRIPTAN	ChEMBL + PubChem	Phase 4 (approved)	HTR1B, HTR1D, HTR1E, HTR1F, HTR2A, HTR2B, HTR2C
TEGASEROD	ChEMBL + PubChem	Phase 4 (approved)	HTR1D, HTR2A, HTR2B, HTR2C, HTR5A, HTR6, HTR7
CINACALCET	ChEMBL	Phase 4 (approved)	HTR1D, HTR2A, HTR2B, HTR2C, HTR5A, HTR6, HTR7
YOHIMBINE	ChEMBL + PubChem	Phase 3 (approved)	HTR1B, HTR1D, HTR1E, HTR1F, HTR2A, HTR2B, HTR6
PENFLURIDOL	ChEMBL	Phase 2	HTR1D, HTR2A, HTR2B, HTR2C, HTR5A, HTR6, HTR7
RITANSERIN	ChEMBL	Phase 2	HTR1B, HTR1E, HTR2A, 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
Pramipexole	ChEMBL + PubChem	Phase 4 (approved)	HTR1B, HTR1E, HTR2A, HTR2B, HTR5A, HTR7
ZIPRASIDONE	ChEMBL + PubChem	Phase 4 (approved)	HTR1E, HTR2A, HTR2B, HTR2C, HTR6, HTR7
ASTEMIZOLE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C, HTR5A, HTR6, HTR7
KETOTIFEN	ChEMBL	Phase 4 (approved)	HTR1B, HTR2A, HTR2B, HTR2C, HTR6, HTR7
MIANSERIN	ChEMBL	Phase 4 (approved)	HTR1D, HTR2A, HTR2B, HTR2C, HTR6, HTR7
OXYMETAZOLINE	ChEMBL	Phase 4 (approved)	HTR1B, HTR1D, HTR2A, HTR2B, HTR2C, HTR6
PROMAZINE	ChEMBL	Phase 4 (approved)	HTR2A, HTR2B, HTR2C, HTR5A, HTR6, HTR7
SALMETEROL	ChEMBL	Phase 4 (approved)	HTR1B, HTR1D, HTR2A, HTR2B, HTR2C, HTR7
GSK163090	ChEMBL	Phase 2	HTR1B, HTR1D, HTR2A, HTR2B, HTR2C, 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
PALIPERIDONE	ChEMBL + PubChem	Phase 4 (approved)	HTR1B, HTR1D, HTR2A, HTR2C, HTR7
ZOLMITRIPTAN	ChEMBL + PubChem	Phase 4 (approved)	HTR1B, HTR1D, HTR1E, HTR1F, HTR2A
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
SERTINDOLE	ChEMBL	Phase 4 (approved)	HTR1B, HTR2A, HTR2B, HTR2C, HTR6
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
VILAZODONE	ChEMBL	Phase 4 (approved)	HTR1B, HTR1D, HTR2B, HTR6, HTR7
XYLOMETAZOLINE	ChEMBL	Phase 4 (approved)	HTR1B, HTR1D, HTR2A, HTR2B, HTR2C
CHLOROPHENYLPIPERAZINE	ChEMBL	Phase 2	HTR2A, HTR2B, HTR2C, HTR6, HTR7