Biomarker & Intervention Discovery

Tension Headache / Chronic Daily Headache

Pharmacologically actionable gene targets, therapeutic agents ranked by evidence tier, and active clinical trials.

Research Tracker / Chronic Disease Interventions / Tension Headache / Chronic Daily Headache

Disease Overview

Spontaneous remission
Not established
Best-intervention remission
—
Gap size
—
Primary barrier
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Biomarker Targets & Therapeutic Agents

Gene targets queried against DGIdb, Open Targets, ChEMBL, PubMed, and Europe PMC. Agents ranked: ● Clinical > ● Mechanistic > ● Correlative.

GRIN2B 238PTGS2 299SCN9A 271TRPV1 160

GRIN2B

UniProt Ensembl DGIdb Open Targets
Therapeutic Agent Effect Direction Evidence Tier Potency Source
DIMIRACETAM ? unclear Mechanistic DGIdb
KETAMINE HYDROCHLORIDE ↓ inhibits Mechanistic DGIdb
PERZINFOTEL ↓ inhibits Mechanistic DGIdb
[3H]CGP39653 ↓ inhibits Mechanistic DGIdb
PHENCYCLIDINE ↓ inhibits Mechanistic DGIdb
DEXANABINOL ? unclear Mechanistic DGIdb
RAPASTINEL ↑ activates Mechanistic DGIdb
DELUCEMINE ↓ inhibits Mechanistic DGIdb
AMANTADINE HYDROCHLORIDE ↓ inhibits Mechanistic DGIdb
RISLENEMDAZ ↓ inhibits Mechanistic DGIdb
ORPHENADRINE CITRATE ↓ inhibits Mechanistic DGIdb
ELIPRODIL ? unclear Mechanistic 13.0 nM (Ki) DGIdb
INDANTADOL ? unclear Mechanistic DGIdb
SEVOFLURANE ? unclear Mechanistic DGIdb
SAGE-718 ~ modulates Mechanistic DGIdb
L689560 ↓ inhibits Mechanistic DGIdb
ONFASPRODIL ~ modulates Mechanistic DGIdb
HOMOQUINOLINIC ACID ↑ activates Mechanistic DGIdb
NEBOGLAMINE ~ modulates Mechanistic DGIdb
DIZOCILPINE ↓ inhibits Mechanistic DGIdb
LY233053 ↓ inhibits Mechanistic DGIdb
GLYCINE ↑ activates Mechanistic DGIdb
ESKETAMINE ~ modulates Mechanistic DGIdb
[3H]CGP61594 ↓ inhibits Mechanistic DGIdb
ORPHENADRINE HYDROCHLORIDE ↓ inhibits Mechanistic DGIdb
[3H]MDL105519 ↓ inhibits Mechanistic DGIdb
RADIPRODIL ? unclear Mechanistic DGIdb
NBQX ? unclear Mechanistic DGIdb
SEMAPIMOD ↓ inhibits Mechanistic DGIdb
SELFOTEL ↓ inhibits Mechanistic DGIdb
SERINE, D- ↑ activates Mechanistic DGIdb
COMPOUND 18C [PMID: 25901531] ↓ inhibits Mechanistic DGIdb
AZD8108 ↓ inhibits Mechanistic DGIdb
[3H]L689560 ↓ inhibits Mechanistic DGIdb
TRAXOPRODIL ↓ inhibits Mechanistic 74.0 nM (IC50) DGIdb
HALOPERIDOL DECANOATE ? unclear Mechanistic DGIdb
N1-DANSYL-SPERMINE ↓ inhibits Mechanistic DGIdb
[3H]D-ASPARTIC ACID ↑ activates Mechanistic DGIdb
NERAMEXANE ? unclear Mechanistic DGIdb
NVP-AAM077 ↓ inhibits Mechanistic DGIdb

Showing top 40 of 238 agents ranked by evidence tier.

PTGS2

UniProt Ensembl DGIdb Open Targets
Therapeutic Agent Effect Direction Evidence Tier Potency Source
CARPROFEN ↓ inhibits Mechanistic 102.0 nM (IC50) DGIdb
INDOMETHACIN SODIUM ↓ inhibits Mechanistic DGIdb
DARBUFELONE ? unclear Mechanistic DGIdb
MEFENAMIC ACID ↓ inhibits Mechanistic DGIdb
MECLOFENAMATE SODIUM ↓ inhibits Mechanistic DGIdb
DICLOFENAC SODIUM ↓ inhibits Mechanistic DGIdb
CAPECITABINE ? unclear Mechanistic DGIdb
PIRPROFEN ↓ inhibits Mechanistic DGIdb
ESFLURBIPROFEN ↓ inhibits Mechanistic DGIdb
SULFASALAZINE ↓ inhibits Mechanistic DGIdb
BROMFENAC ? unclear Mechanistic DGIdb
IBUPROFEN, SODIUM SALT ↓ inhibits Mechanistic DGIdb
ALOXIPRIN ↓ inhibits Mechanistic DGIdb
TENOXICAM ? unclear Mechanistic DGIdb
FLURBIPROFEN ↓ inhibits Mechanistic DGIdb
SALICYLIC ACID ? unclear Mechanistic DGIdb
ATENOLOL ? unclear Mechanistic DGIdb
DEXKETOPROFEN ↓ inhibits Mechanistic DGIdb
ETORICOXIB ↓ inhibits Mechanistic DGIdb
LUMIRACOXIB ↓ inhibits Mechanistic DGIdb
SUPROFEN ↓ inhibits Mechanistic DGIdb
NS-398 ? unclear Mechanistic DGIdb
NABUMETONE ↓ inhibits Mechanistic DGIdb
URSOLIC ACID ? unclear Mechanistic DGIdb
IBUPROFEN LYSINE ↓ inhibits Mechanistic DGIdb
ACECLOFENAC ↓ inhibits Mechanistic DGIdb
IBUFENAC ↓ inhibits Mechanistic DGIdb
BALSALAZIDE ? unclear Mechanistic DGIdb
DIFLUNISAL ↓ inhibits Mechanistic DGIdb
BALSALAZIDE DISODIUM ↓ inhibits Mechanistic DGIdb
VACCINE ? unclear Mechanistic DGIdb
KETOROLAC TROMETHAMINE ↓ inhibits Mechanistic DGIdb
BENZYDAMINE HYDROCHLORIDE ↓ inhibits Mechanistic DGIdb
TIAPROFENIC ACID ? unclear Mechanistic DGIdb
RALOXIFENE HYDROCHLORIDE ? unclear Mechanistic DGIdb
NAPROXCINOD ↓ inhibits Mechanistic DGIdb
IGURATIMOD ↓ inhibits Mechanistic DGIdb
ETODOLAC ↓ inhibits Mechanistic DGIdb
DICLOFENAC ETALHYALURONATE SODIUM ↓ inhibits Mechanistic DGIdb
ROFECOXIB ↓ inhibits Mechanistic 530.0 nM (IC50) DGIdb

Showing top 40 of 299 agents ranked by evidence tier.

SCN9A

UniProt Ensembl DGIdb Open Targets
Therapeutic Agent Effect Direction Evidence Tier Potency Source
MERETHOXYLLINE PROCAINE ↓ inhibits Mechanistic DGIdb
ETIDOCAINE HYDROCHLORIDE ↓ inhibits Mechanistic DGIdb
FOSPHENYTOIN ↓ inhibits Mechanistic DGIdb
VERATRIDINE ↑ activates Mechanistic DGIdb
ORPHENADRINE CITRATE ↓ inhibits Mechanistic DGIdb
PHENACEMIDE ↓ inhibits Mechanistic DGIdb
LACOSAMIDE ↓ inhibits Mechanistic DGIdb
VIXOTRIGINE ↓ inhibits Mechanistic DGIdb
DSP-2230 ↓ inhibits Mechanistic DGIdb
SAXITOXIN ↓ inhibits Mechanistic DGIdb
ESLICARBAZEPINE ACETATE ↓ inhibits Mechanistic DGIdb
SAFINAMIDE ? unclear Mechanistic DGIdb
LIDOCAINE ↓ inhibits Mechanistic DGIdb
RILUZOLE ↓ inhibits Mechanistic DGIdb
ROPIVACAINE HYDROCHLORIDE ↓ inhibits Mechanistic DGIdb
FUNAPIDE ↓ inhibits Mechanistic DGIdb
DYCLONINE HYDROCHLORIDE ↓ inhibits Mechanistic DGIdb
EVENAMIDE ↓ inhibits Mechanistic DGIdb
PROPOFOL ? unclear Mechanistic DGIdb
AM-6120 ↓ inhibits Mechanistic DGIdb
RG7893 ↓ inhibits Mechanistic DGIdb
RG6029 ↓ inhibits Mechanistic DGIdb
QUINIDINE SULFATE ↓ inhibits Mechanistic DGIdb
ZONISAMIDE ↓ inhibits Mechanistic DGIdb
NERISPIRDINE ↓ inhibits Mechanistic DGIdb
RALFINAMIDE ↓ inhibits Mechanistic DGIdb
DS-1971A ↓ inhibits Mechanistic DGIdb
HEXYLCAINE HYDROCHLORIDE ↓ inhibits Mechanistic DGIdb
MEPIVACAINE HYDROCHLORIDE ↓ inhibits Mechanistic DGIdb
PROCAINAMIDE HYDROCHLORIDE ↓ inhibits Mechanistic DGIdb
PROPAFENONE HYDROCHLORIDE ↓ inhibits Mechanistic DGIdb
LIDOCAINE HYDROCHLORIDE ↓ inhibits Mechanistic DGIdb
QUINIDINE GLUCONATE ↓ inhibits Mechanistic DGIdb
PRILOCAINE ↓ inhibits Mechanistic DGIdb
ETHOTOIN ↓ inhibits Mechanistic DGIdb
PF-05089771 ↓ inhibits Mechanistic DGIdb
DICHLOROBENZYL ALCOHOL ↓ inhibits Mechanistic DGIdb
RANOLAZINE ? unclear Mechanistic DGIdb
PRILOCAINE HYDROCHLORIDE ↓ inhibits Mechanistic DGIdb
ORPHENADRINE HYDROCHLORIDE ↓ inhibits Mechanistic DGIdb

Showing top 40 of 271 agents ranked by evidence tier.

TRPV1

UniProt Ensembl DGIdb Open Targets
Therapeutic Agent Effect Direction Evidence Tier Potency Source
STREPTOZOCIN ? unclear Mechanistic DGIdb
BENZYL ISOTHIOCYANATE ? unclear Mechanistic DGIdb
ACETAMINOPHEN ↑ activates Mechanistic DGIdb
POLYGODIAL ? unclear Mechanistic DGIdb
PROPOFOL ? unclear Mechanistic DGIdb
SAF312 ↓ inhibits Mechanistic DGIdb
GRC-15300 ? unclear Mechanistic DGIdb
AZD1386 ↓ inhibits Mechanistic DGIdb
TIVANISIRAN ↓ inhibits Mechanistic DGIdb
MAVATREP ↓ inhibits Mechanistic DGIdb
MR-1817 ↓ inhibits Mechanistic DGIdb
FERRUGINENE B ? unclear Mechanistic DGIdb
CAPSAICIN ↑ activates Mechanistic 19.95 nM (EC50) DGIdb
RECOMBINANT TUMOR NECROSIS FACTOR FAMILY PROTEIN ? unclear Mechanistic DGIdb
PHENETHYLISOTHIOCYANATE ? unclear Mechanistic DGIdb
VOACANGINE ? unclear Mechanistic DGIdb
RESINIFERATOXIN ↑ activates Mechanistic 23.1 nM (Ki) DGIdb
DWP05195 ↓ inhibits Mechanistic DGIdb
XEN-D0501 ↓ inhibits Mechanistic DGIdb
PAC-14028 ↓ inhibits Mechanistic DGIdb
SB-705498 ↓ inhibits Mechanistic DGIdb
MASOPROCOL ? unclear Mechanistic DGIdb
ALLYL ISOTHIOCYANATE ? unclear Mechanistic DGIdb
NGD-8243 ↓ inhibits Mechanistic DGIdb
GRC-6211 ↓ inhibits Mechanistic DGIdb
RESERPINE ? unclear Mechanistic DGIdb
NABIXIMOLS ? unclear Mechanistic DGIdb
A425619 ? unclear Mechanistic DGIdb
PHE377 ↓ inhibits Mechanistic DGIdb
ANTISENSE OLIGONUCLEOTIDES ? unclear Mechanistic DGIdb
WORTMANNIN ? unclear Mechanistic DGIdb
JTS-653 ↓ inhibits Mechanistic DGIdb
LEVODOPA ? unclear Mechanistic DGIdb
AMG517 ↓ inhibits Mechanistic DGIdb
CAPSAZEPINE ? unclear Mechanistic 120.0 nM (Ki) DGIdb
ZUCAPSAICIN ↑ activates Mechanistic DGIdb
INDOMETHACIN ? unclear Mechanistic DGIdb
CHEMBL:CHEMBL191534 ? unclear Mechanistic DGIdb
ABT-102 ↓ inhibits Mechanistic DGIdb
ISOPROPYL ISOTHIOCYANATE ? unclear Mechanistic DGIdb

Showing top 40 of 160 agents ranked by evidence tier.

Clinical Trials

Recruiting and recently completed trials from ClinicalTrials.gov. Data retrieved 2026-07-03.

Analysis of Headache Chronification With Imaging, Deep Phenotyping, and Proteomics Recruiting
NCT03231241 Phase: N/A Started: 2014-12-12

Study is aimed at determining why some patients with episodic headache proceed to chronic daily or near daily headaches. The Investigators seek to discover differences in brain anatomy and function, composition of cerebrospinal fluid, blood products, genetics, and patient phenotypes that might help ...

Headstrong Intervention for Pediatric Headache Completed
NCT00269581 Phase: PHASE3 Started: 2004-08

Purpose of this study is to determine if a CD-ROM computer program (called "Headstrong") is effective in helping children cope with chronic headaches.

Agents Found By Disease-Level Search

Searched directly from “Tension Headache / Chronic Daily Headache” via ClinicalTrials.gov interventions and Open Targets' disease→drug data — independent of the 4-gene target panel above. This surfaces agents whose mechanism doesn't route through a curated gene (combination therapies, standard-of-care drugs, targets outside the panel).

Not yet run. python -m biomarker_pipeline.run_disease_agent_discovery --disease "..."

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