TONABERSAT Property

Boiling point:

554.5±50.0 °C(Predicted)

Density 

1.38

storage temp. 

2-8°C

solubility 

Soluble in DMSO

pka

11.86±0.60(Predicted)

form 

powder

color 

white to beige

optical activity

[α]/D -100 to -110°, c = 1 in methanol

Safety

RIDADR 

UN 3077 9 / PGIII

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H315Causes skin irritation

H319Causes serious eye irritation

H400Very toxic to aquatic life

Precautionary statements

P273Avoid release to the environment.

P280Wear protective gloves/protective clothing/eye protection/face protection.

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

P337+P313IF eye irritation persists: Get medical advice/attention.

P391Collect spillage. Hazardous to the aquatic environment

TONABERSAT Chemical Properties,Usage,Production

Uses

It is a cholinesterase inhibitor for treating and preventing migraine. An antimigraine agent.

Biological Activity

migraine is a common, recurrent and primary headache disorder. optimisation of novel cis- and trans-4-(substituted-anfido)benzopyran-3-ol derivatives has led to the identification of tonabersat (sb-220453) with potential antimigraine activity.

Biochem/physiol Actions

Tonabersat (SB-220453) exhibits anticonvulsant property. It is a member of the family of novel benzoylamino-benzopyran compounds. Tonabersat is used as a therapeutic for trigeminal nerve-induced neurovascular reflexes. In addition, it acts as a putative migraine prophylactic agent containing an unique stereospecific binding site in the brain.

in vitro

topiramate targets multiple cortical and subcortical loci, altering voltage-gated ion channels and chemical transmission to decrease abnormal brain excitability. preclinical studies have identified four properties that may account for the drug’s efficacy in epilepsy and migraine prophylaxis: (i) blockage of voltage-dependent sodium channels; (ii) augmentation of the activity of the neurotransmitter g-aminobutyric acid (gaba) at some subtypes of the gaba-a receptor; (iii) antagonism of the ampa/kainate subtype of the glutamate receptor; and (iv) inhibition of the carbonic anhydrase enzymes, particularly isozymes ii and iv [1].

in vivo

tonabersat binds selectively to a unique site in the brain. moreover, tonabersat could markedly reduce cortical spreading depression (csd) and csd-associated events and inhibite gap-junction communication between neurons and satellite glial cells in the trigeminal ganglion. together, these findings indicate that tonabersat should have clinical application in preventing migraine attacks [2].

References

[1] silberstein sd. tonabersat, a novel gap-junction modulator for the prevention of migraine. cephalalgia. 2009;29 suppl 2:28-35.
[2] durham pl, garrett fg. neurological mechanisms of migraine: potential of the gap-junction modulator tonabersat in prevention of migraine. cephalalgia. 2009;29 suppl 2:1-6.
[3] hauge aw, asghar ms, schytz hw, christensen k, olesen j. effects of tonabersat on migraine with aura: a randomised, double-blind, placebo-controlled crossover study. lancet neurol. 2009;8(8):718-23.