Rizatriptan

Summary

Rizatriptan (CHEMBL905) is an approved small-molecule serotonergic agonist (ATC N02CC04) targeting HTR1A, HTR1B, and HTR1D; indicated across 3 conditions including migraine disorder and migraine with aura.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: N02CC04
• Targets: 5 (HTR1A, HTR1B, HTR1D…)
• Indications: 3 conditions
• Clinical trials: 12
• Chemistry: 269.34 Da · C15H19N5

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL905
Name	Rizatriptan
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	5078
ChEBI	CHEBI:48273
ATC	N02CC04
Molecular formula	C15H19N5
Molecular weight	269.34
InChIKey	ULFRLSNUDGIQQP-UHFFFAOYSA-N

SMILES: CN(C)CCC1=CNC2=C1C=C(C=C2)CN3C=NC=N3

IUPAC name: N,N-dimethyl-2-[5-(1,2,4-triazol-1-ylmethyl)-1H-indol-3-yl]ethanamine

Pharmacological roles (ChEBI): serotonergic agonist, vasoconstrictor agent, anti-inflammatory drug.

Also known as: L-705126, Maxalt, MK-462 FREE BASE, Rizatriptan, rizatriptan, SID174007052, SID144205087, RIZATRIPTAN, Rizatriptan Benzoate (Maxalt)

Parent form; salt/anhydrous children: CHEMBL1201032, CHEMBL3989629

Patent coverage: 3,335 distinct patent families (13,722 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 13,717 (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
HTR1A	5-HT1A receptor	Full agonist	6.4	0%	P08908
HTR1B	5-HT1B receptor	Partial agonist	6.9	0.2%	P28222
HTR1D	5-HT1D receptor	Full agonist	7.9	0%	P28221
HTR1E	5-ht1e receptor	Full agonist	6.8	0%	P28566
HTR1F	5-HT1F receptor	Full agonist	6.8	0.1%	P30939

Broader ChEMBL bioactivity targets: 11 (assay-derived). Sample: 5-hydroxytryptamine receptor 2B, 5-hydroxytryptamine receptor 1B, Alpha-2C adrenergic receptor, 5-hydroxytryptamine receptor 1D, Serotonin 3 (5-HT3) receptor, 5-hydroxytryptamine receptor 1A, 5-hydroxytryptamine receptor 2A, 5-hydroxytryptamine receptor 2C, Histamine H1 receptor, 5-hydroxytryptamine receptor 2A.

Bioactivity

ChEMBL activities: 24 potent at pChembl ≥ 5 of 28 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
HTR1B	8.52	Ki	3	nM	CHEMBL_ACT_25553869
HTR1D	8.52	Ki	3	nM	CHEMBL_ACT_25553874
HTR1D	8.52	EC50	3	nM	CHEMBL_ACT_786215
HTR1D	8.37	Ki	4.3	nM	CHEMBL_ACT_786212
HTR1D	8.08	EC50	8.4	nM	CHEMBL_ACT_773047
HTR1B	8	Ki	10.1	nM	CHEMBL_ACT_786214
HTR1D	7.96	IC50	11	nM	CHEMBL_ACT_773045
HTR1D	7.87	Ki	13.5	nM	CHEMBL_ACT_463418
HTR1D	7.4	Ki	40	nM	CHEMBL_ACT_463419
HTR1B	7.39	IC50	41	nM	CHEMBL_ACT_773046
P79400	7.3	IC50	50.12	nM	CHEMBL_ACT_89500
HTR1D	7.1	IC50	79.43	nM	CHEMBL_ACT_89508
HTR1A	6.85	Ki	140	nM	CHEMBL_ACT_786213
HTR1A	6.53	Ki	293	nM	CHEMBL_ACT_463420
HTR1A	6.5	IC50	316.2	nM	CHEMBL_ACT_89502
HTR1A	6.4	IC50	398.1	nM	CHEMBL_ACT_89509
HTR1A	5.75	AC50	1776	nM	CHEMBL_ACT_25164341
HTR1A	5.5	AC50	3200	nM	CHEMBL_ACT_25216515
P35563	5.4	IC50	3981	nM	CHEMBL_ACT_89505
HRH1	5.24	AC50	5795	nM	CHEMBL_ACT_25211977
P14842	5.2	IC50	6310	nM	CHEMBL_ACT_89504
HTR2A	5.11	AC50	7746	nM	CHEMBL_ACT_25225831
HTR2C	5.1	IC50	7943	nM	CHEMBL_ACT_89503
HTR2A	5.1	IC50	7943	nM	CHEMBL_ACT_89511

Target pathways

Aggregated over 5 target gene(s): HTR1A, HTR1B, HTR1D, HTR1E, HTR1F.

Top Reactome pathways

8 total, by targets touching each:

Pathway	Targets	Genes
Signal Transduction	5	HTR1A, HTR1B, HTR1D, HTR1E, HTR1F
Signaling by GPCR	5	HTR1A, HTR1B, HTR1D, HTR1E, HTR1F
Class A/1 (Rhodopsin-like receptors)	5	HTR1A, HTR1B, HTR1D, HTR1E, HTR1F
Amine ligand-binding receptors	5	HTR1A, HTR1B, HTR1D, HTR1E, HTR1F
Serotonin receptors	5	HTR1A, HTR1B, HTR1D, HTR1E, HTR1F
GPCR ligand binding	5	HTR1A, HTR1B, HTR1D, HTR1E, HTR1F
GPCR downstream signalling	4	HTR1B, HTR1D, HTR1E, HTR1F
G alpha (i) signalling events	4	HTR1B, HTR1D, HTR1E, HTR1F

Dominant GO biological processes

GO term	Targets
G protein-coupled receptor signaling pathway	5
G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger	5
adenylate cyclase-inhibiting serotonin receptor signaling pathway	5
chemical synaptic transmission	5
signal transduction	5
adenylate cyclase-activating G protein-coupled receptor signaling pathway	4
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	4
regulation of behavior	3
vasoconstriction	2
behavioral fear response	1
serotonin receptor signaling pathway	1
gamma-aminobutyric acid signaling pathway	1
positive regulation of cell population proliferation	1
regulation of serotonin secretion	1
regulation of vasoconstriction	1

Indications & clinical

Indications

3 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
migraine with aura	3	MONDO:0005475	MONDO:0005475
migraine without aura	3	MONDO:0100431	MONDO:0100431

Clinical trials

Total trials: 12.

Phase distribution

Phase	Trials
PHASE3	5
PHASE4	3
Not specified	2
PHASE2/PHASE3	1
PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00397254	PHASE4	COMPLETED	Two Rizatriptan Prescribing Portions for Treatment of Migraine
NCT00719134	PHASE4	COMPLETED	The Effects of Expectation and Knowledge on Rizatriptan and Placebo Treatment of Acute Migraine Headache
NCT01057160	PHASE4	COMPLETED	Rizatriptan 10 MG RPD in the Treatment of Acute Migraine
NCT00250458	PHASE3	COMPLETED	Study to Test a Marketed Product in the Treatment of Migraine-associated Nausea
NCT00894556	PHASE3	COMPLETED	A Study to Evaluate the Efficacy and Tolerability of Rizatriptan for Treatment of Acute Migraine (0462-087)
NCT01001234	PHASE3	COMPLETED	A Study to Evaluate the Efficacy and Tolerability of Rizatriptan for Treatment of Acute Migraine in Children and Adolescents (MK-0462-082 AM7)
NCT01286207	PHASE3	COMPLETED	Long-Term Exposure to Rizatriptan 5-mg and 10-mg Oral Tablet (Combined Extension Protocols MK-0462-022, MK-0462-025, MK-0462-029)
NCT02447991	PHASE2/PHASE3	COMPLETED	Rizatriptan for Episodic Dizziness in Vestibular Migraine
NCT03896009	PHASE3	COMPLETED	Maximizing Outcomes in Treating Acute Migraine
NCT00246337	PHASE2	COMPLETED	A Dose-Finding Study of MK0974 in Acute Migraine (MK0974-004)
NCT00360282	Not specified	COMPLETED	Does a Migraine Medication Decrease Rotational Motion Sickness in People Suffering From Migraines?
NCT01306266	Not specified	WITHDRAWN	Study of Rizatriptan in the Treatment of Acute Attacks of Post-traumatic Headache in U.S. Military Troops

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 12 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.

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

Molecule	Source	Status	Shared targets
DIHYDROERGOTAMINE	ChEMBL + PubChem	Phase 4 (approved)	HTR1A, HTR1B, HTR1D, HTR1E, HTR1F
ERGOTAMINE	ChEMBL + PubChem	Phase 4 (approved)	HTR1A, HTR1B, HTR1D, HTR1E, HTR1F
IMIPRAMINE	ChEMBL + PubChem	Phase 4 (approved)	HTR1A, HTR1B, HTR1D, HTR1E, HTR1F
NARATRIPTAN	ChEMBL + PubChem	Phase 4 (approved)	HTR1A, HTR1B, HTR1D, HTR1E, HTR1F
RISPERIDONE	ChEMBL + PubChem	Phase 4 (approved)	HTR1A, HTR1B, HTR1D, HTR1E, HTR1F
SUMATRIPTAN	ChEMBL + PubChem	Phase 4 (approved)	HTR1A, HTR1B, HTR1D, HTR1E, HTR1F
ZOLMITRIPTAN	ChEMBL + PubChem	Phase 4 (approved)	HTR1A, HTR1B, HTR1D, HTR1E, HTR1F
SEROTONIN	ChEMBL + PubChem	Phase 3 (approved)	HTR1A, HTR1B, HTR1D, HTR1E, HTR1F
YOHIMBINE	ChEMBL + PubChem	Phase 3 (approved)	HTR1A, HTR1B, HTR1D, HTR1E, HTR1F
MEBUFOTENIN	ChEMBL	Phase 2	HTR1A, HTR1B, HTR1D, HTR1E, HTR1F
CLOZAPINE	ChEMBL + PubChem	Phase 4 (approved)	HTR1A, HTR1B, HTR1E, HTR1F
ELETRIPTAN	ChEMBL + PubChem	Phase 4 (approved)	HTR1A, HTR1B, HTR1E, HTR1F
OLANZAPINE	ChEMBL + PubChem	Phase 4 (approved)	HTR1A, HTR1B, HTR1E, HTR1F
BREXPIPRAZOLE	ChEMBL	Phase 4 (approved)	HTR1A, HTR1B, HTR1D, HTR1E
FROVATRIPTAN	ChEMBL	Phase 4 (approved)	HTR1A, HTR1B, HTR1D, HTR1E
PSILOCIN	ChEMBL	Phase 2	HTR1A, HTR1B, HTR1D, HTR1E
CYPROHEPTADINE	ChEMBL + PubChem	Phase 4 (approved)	HTR1A, HTR1E, HTR1F
LASMIDITAN	ChEMBL + PubChem	Phase 4 (approved)	HTR1D, HTR1E, HTR1F
METHYLERGONOVINE	ChEMBL + PubChem	Phase 4 (approved)	HTR1A, HTR1E, HTR1F
PRAMIPEXOLE	ChEMBL + PubChem	Phase 4 (approved)	HTR1A, HTR1B, HTR1E
QUETIAPINE	ChEMBL + PubChem	Phase 4 (approved)	HTR1A, HTR1E, HTR1F
SORAFENIB	ChEMBL + PubChem	Phase 4 (approved)	HTR1A, HTR1E, HTR1F
ARIPIPRAZOLE	ChEMBL	Phase 4 (approved)	HTR1A, HTR1B, HTR1D
AZELASTINE	ChEMBL	Phase 4 (approved)	HTR1B, HTR1D, HTR1E
CARIPRAZINE	ChEMBL	Phase 4 (approved)	HTR1A, HTR1B, HTR1D
KETANSERIN	ChEMBL	Phase 4 (approved)	HTR1A, HTR1B, HTR1D
NEFAZODONE	ChEMBL	Phase 4 (approved)	HTR1A, HTR1B, HTR1D
OXYMETAZOLINE	ChEMBL	Phase 4 (approved)	HTR1A, HTR1B, HTR1D
SALMETEROL	ChEMBL	Phase 4 (approved)	HTR1A, HTR1B, HTR1D
SILODOSIN	ChEMBL	Phase 4 (approved)	HTR1A, HTR1B, HTR1D
VILAZODONE	ChEMBL	Phase 4 (approved)	HTR1A, HTR1B, HTR1D
XYLOMETAZOLINE	ChEMBL	Phase 4 (approved)	HTR1A, HTR1B, HTR1D
ACETRYPTINE	ChEMBL	Phase 2	HTR1A, HTR1B, HTR1D
GSK163090	ChEMBL	Phase 2	HTR1A, HTR1B, HTR1D
LYSERGIDE	ChEMBL	Phase 2	HTR1A, HTR1D, HTR1E
RITANSERIN	ChEMBL	Phase 2	HTR1A, HTR1B, HTR1E
ASENAPINE	ChEMBL + PubChem	Phase 4 (approved)	HTR1A, HTR1E
CANNABIDIOL	ChEMBL + PubChem	Phase 4 (approved)	HTR1A, HTR1E
PALIPERIDONE	ChEMBL + PubChem	Phase 4 (approved)	HTR1B, HTR1D
ZIPRASIDONE	ChEMBL + PubChem	Phase 4 (approved)	HTR1A, HTR1E
CINACALCET	ChEMBL	Phase 4 (approved)	HTR1A, HTR1D
LOPERAMIDE	ChEMBL	Phase 4 (approved)	HTR1A, HTR1D
MIANSERIN	ChEMBL	Phase 4 (approved)	HTR1A, HTR1D
PINDOLOL	ChEMBL	Phase 4 (approved)	HTR1A, HTR1B
PRAZOSIN	ChEMBL	Phase 4 (approved)	HTR1A, HTR1D
SERTINDOLE	ChEMBL	Phase 4 (approved)	HTR1A, HTR1B
TEGASEROD	ChEMBL	Phase 4 (approved)	HTR1A, HTR1D
LATREPIRDINE	ChEMBL	Phase 3	HTR1D, HTR1E
ALNIDITAN	ChEMBL	Phase 2	HTR1A, HTR1D
MAZAPERTINE	ChEMBL	Phase 2	HTR1A, HTR1B
NIGULDIPINE	ChEMBL	Phase 2	HTR1A, HTR1B
PENFLURIDOL	ChEMBL	Phase 2	HTR1A, HTR1D
SPIRAMIDE	ChEMBL	Phase 2	HTR1A, HTR1D
ACEMETACIN	ChEMBL	Phase 4 (approved)	HTR1A
ACETOPHENAZINE	ChEMBL	Phase 4 (approved)	HTR1A
ACETYLCHOLINE	ChEMBL	Phase 4 (approved)	HTR1A
ALMOTRIPTAN	ChEMBL	Phase 4 (approved)	HTR1A
AMILORIDE	ChEMBL	Phase 4 (approved)	HTR1A
AMITRIPTYLINE	ChEMBL	Phase 4 (approved)	HTR1A
AMLODIPINE	ChEMBL	Phase 4 (approved)	HTR1A