U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C20H19ClFNO4
Molecular Weight 391.821
Optical Activity UNSPECIFIED
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of TONABERSAT

SMILES

CC(=O)C1=CC2=C(OC(C)(C)[C@@H](O)[C@H]2NC(=O)C3=CC=C(F)C(Cl)=C3)C=C1

InChI

InChIKey=XLIIRNOPGJTBJD-ROUUACIJSA-N
InChI=1S/C20H19ClFNO4/c1-10(24)11-5-7-16-13(8-11)17(18(25)20(2,3)27-16)23-19(26)12-4-6-15(22)14(21)9-12/h4-9,17-18,25H,1-3H3,(H,23,26)/t17-,18-/m0/s1

HIDE SMILES / InChI

Description
Curator's Comment: description was created on several sources, including https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3142555/

Tonabersat is a unique compound with demonstrated activity as a gap-junction inhibitor in animal studies. In preclinical and clinical trials, tonabersat was well tolerated, with no cardiovascular effects; the pharmacokinetic profile suggested its usefulness in the prophylaxis of migraine. The basis of its high efficacy is inhibiting neuronal hyperexcitability and trigeminal nerve stimulated neurogenic inflammation in rodent models. Tonabersat inhibits the CSD (cortical spreading depression) that is believed to underlie the aura of migraine.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: map04540
Sources: www.ncbi.nlm.nih.gov/pubmed/24611055
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Preventing
Unknown

Approved Use

Unknown
Preventing
Unknown

Approved Use

Unknown
Doses

Doses

DosePopulationAdverse events​
80 mg single, oral (unknown)
Highest studied dose
Dose: 80 mg
Route: oral
Route: single
Dose: 80 mg
Sources:
unhealthy
n = 109
Health Status: unhealthy
Condition: migraine
Sex: M+F
Food Status: UNKNOWN
Population Size: 109
Sources:
Other AEs: Dizziness, Nausea...
Other AEs:
Dizziness (5.5%)
Nausea (4.6%)
Vertigo (4.6%)
Somnolence (0.9%)
Abdominal pain (0.9%)
Sources:
40 mg 1 times / day multiple, oral (total daily dose)
Dose: 40 mg, 1 times / day
Route: oral
Route: multiple
Dose: 40 mg, 1 times / day
Sources:
unhealthy
n = 58
Health Status: unhealthy
Condition: migraine
Sex: M+F
Food Status: UNKNOWN
Population Size: 58
Sources:
Disc. AE: dizziness, nausea...
AEs leading to
discontinuation/dose reduction:
dizziness (1 pt)
nausea (2 patients)
nausea (1 pt)
Drowsiness (severe, 1 pt)
headache (1 pt)
Sources:
AEs

AEs

AESignificanceDosePopulation
Abdominal pain 0.9%
80 mg single, oral (unknown)
Highest studied dose
Dose: 80 mg
Route: oral
Route: single
Dose: 80 mg
Sources:
unhealthy
n = 109
Health Status: unhealthy
Condition: migraine
Sex: M+F
Food Status: UNKNOWN
Population Size: 109
Sources:
Somnolence 0.9%
80 mg single, oral (unknown)
Highest studied dose
Dose: 80 mg
Route: oral
Route: single
Dose: 80 mg
Sources:
unhealthy
n = 109
Health Status: unhealthy
Condition: migraine
Sex: M+F
Food Status: UNKNOWN
Population Size: 109
Sources:
Nausea 4.6%
80 mg single, oral (unknown)
Highest studied dose
Dose: 80 mg
Route: oral
Route: single
Dose: 80 mg
Sources:
unhealthy
n = 109
Health Status: unhealthy
Condition: migraine
Sex: M+F
Food Status: UNKNOWN
Population Size: 109
Sources:
Vertigo 4.6%
80 mg single, oral (unknown)
Highest studied dose
Dose: 80 mg
Route: oral
Route: single
Dose: 80 mg
Sources:
unhealthy
n = 109
Health Status: unhealthy
Condition: migraine
Sex: M+F
Food Status: UNKNOWN
Population Size: 109
Sources:
Dizziness 5.5%
80 mg single, oral (unknown)
Highest studied dose
Dose: 80 mg
Route: oral
Route: single
Dose: 80 mg
Sources:
unhealthy
n = 109
Health Status: unhealthy
Condition: migraine
Sex: M+F
Food Status: UNKNOWN
Population Size: 109
Sources:
dizziness 1 pt
Disc. AE
40 mg 1 times / day multiple, oral (total daily dose)
Dose: 40 mg, 1 times / day
Route: oral
Route: multiple
Dose: 40 mg, 1 times / day
Sources:
unhealthy
n = 58
Health Status: unhealthy
Condition: migraine
Sex: M+F
Food Status: UNKNOWN
Population Size: 58
Sources:
headache 1 pt
Disc. AE
40 mg 1 times / day multiple, oral (total daily dose)
Dose: 40 mg, 1 times / day
Route: oral
Route: multiple
Dose: 40 mg, 1 times / day
Sources:
unhealthy
n = 58
Health Status: unhealthy
Condition: migraine
Sex: M+F
Food Status: UNKNOWN
Population Size: 58
Sources:
nausea 1 pt
Disc. AE
40 mg 1 times / day multiple, oral (total daily dose)
Dose: 40 mg, 1 times / day
Route: oral
Route: multiple
Dose: 40 mg, 1 times / day
Sources:
unhealthy
n = 58
Health Status: unhealthy
Condition: migraine
Sex: M+F
Food Status: UNKNOWN
Population Size: 58
Sources:
nausea 2 patients
Disc. AE
40 mg 1 times / day multiple, oral (total daily dose)
Dose: 40 mg, 1 times / day
Route: oral
Route: multiple
Dose: 40 mg, 1 times / day
Sources:
unhealthy
n = 58
Health Status: unhealthy
Condition: migraine
Sex: M+F
Food Status: UNKNOWN
Population Size: 58
Sources:
Drowsiness severe, 1 pt
Disc. AE
40 mg 1 times / day multiple, oral (total daily dose)
Dose: 40 mg, 1 times / day
Route: oral
Route: multiple
Dose: 40 mg, 1 times / day
Sources:
unhealthy
n = 58
Health Status: unhealthy
Condition: migraine
Sex: M+F
Food Status: UNKNOWN
Population Size: 58
Sources:
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Identification of (-)-cis-6-acetyl-4S-(3-chloro-4-fluoro-benzoylamino)- 3,4-dihydro-2,2-dimethyl-2H-benzo[b]pyran-3S-ol as a potential antimigraine agent.
1999 Jan 18
The potential anti-migraine compound SB-220453 does not contract human isolated blood vessels or myocardium; a comparison with sumatriptan.
2000 Jul
Repetitive cortical spreading depression in a gyrencephalic feline brain: inhibition by the novel benzoylamino-benzopyran SB-220453.
2000 Jul
SB-220453, a potential novel antimigraine agent, inhibits nitric oxide release following induction of cortical spreading depression in the anaesthetized cat.
2000 Mar
Tonabersat (SB-220453) a novel benzopyran with anticonvulsant properties attenuates trigeminal nerve-induced neurovascular reflexes.
2001 Apr
A double-blind study of SB-220453 (Tonerbasat) in the glyceryltrinitrate (GTN) model of migraine.
2004 Oct
Tonabersat inhibits trigeminal ganglion neuronal-satellite glial cell signaling.
2009 Jan
Patents

Sample Use Guides

Take 40 mg daily for 12 weeks.
Route of Administration: Oral
In Vitro Use Guide
Unknown
Name Type Language
TONABERSAT
INN   WHO-DD  
INN  
Official Name English
tonabersat [INN]
Common Name English
Tonabersat [WHO-DD]
Common Name English
SB-220453
Code English
Classification Tree Code System Code
NCI_THESAURUS C264
Created by admin on Thu Jul 06 22:17:27 UTC 2023 , Edited by admin on Thu Jul 06 22:17:27 UTC 2023
Code System Code Type Description
DRUG BANK
DB06578
Created by admin on Thu Jul 06 22:17:27 UTC 2023 , Edited by admin on Thu Jul 06 22:17:27 UTC 2023
PRIMARY
FDA UNII
2XD9773ZMN
Created by admin on Thu Jul 06 22:17:27 UTC 2023 , Edited by admin on Thu Jul 06 22:17:27 UTC 2023
PRIMARY
EPA CompTox
DTXSID40169923
Created by admin on Thu Jul 06 22:17:27 UTC 2023 , Edited by admin on Thu Jul 06 22:17:27 UTC 2023
PRIMARY
NCI_THESAURUS
C97277
Created by admin on Thu Jul 06 22:17:27 UTC 2023 , Edited by admin on Thu Jul 06 22:17:27 UTC 2023
PRIMARY
INN
7765
Created by admin on Thu Jul 06 22:17:27 UTC 2023 , Edited by admin on Thu Jul 06 22:17:27 UTC 2023
PRIMARY
CAS
175013-84-0
Created by admin on Thu Jul 06 22:17:27 UTC 2023 , Edited by admin on Thu Jul 06 22:17:27 UTC 2023
PRIMARY
EVMPD
SUB79261
Created by admin on Thu Jul 06 22:17:27 UTC 2023 , Edited by admin on Thu Jul 06 22:17:27 UTC 2023
PRIMARY
PUBCHEM
6918324
Created by admin on Thu Jul 06 22:17:27 UTC 2023 , Edited by admin on Thu Jul 06 22:17:27 UTC 2023
PRIMARY
MESH
C118706
Created by admin on Thu Jul 06 22:17:27 UTC 2023 , Edited by admin on Thu Jul 06 22:17:27 UTC 2023
PRIMARY
ChEMBL
CHEMBL318191
Created by admin on Thu Jul 06 22:17:27 UTC 2023 , Edited by admin on Thu Jul 06 22:17:27 UTC 2023
PRIMARY
SMS_ID
100000138878
Created by admin on Thu Jul 06 22:17:27 UTC 2023 , Edited by admin on Thu Jul 06 22:17:27 UTC 2023
PRIMARY