Tonabersat

Tonabersat is a gap-junction modulator.

Signaling Pathways >> Cytoskeleton >> Gap Junction Protein

Research Areas >> Neurological Disease

Gap-junction[1]

Tonabersat, a novel benzopyran derivative, inhibits cortical spreading depression (CSD) and therefore might be able to inhibit the early migraine mechanisms[1].

Treatment with either Tonabersat (10 mg/kg) or Meclofenamate (20 mg/kg) as single agents significantly inhibit progression of metastatic lesions. Addition of carboplatin to either agent profoundly inhibits brain metastasis[2].

Mice[2] Athymic NCR nu/nu mice, Cr:NIH bg-nu-xid mice, B6129SF1/J, C57BL/6J-Tmem173gt/J 'golden ticket', and C57/Bl/6J mice are used at 5-6 weeks of age. For inducible knockdown experiments, mice are given doxycycline hyclate in the drinking water (2 mg/mL) and the diet 14 days after injection of cancer cells. For drug treatment experiments, mice are intraperitoneally injected with Carboplatin (5 mg/kg per 5 days), Tonabersat (MedChem Express) (10 mg/kg per day), or meclofenamic acid sodium salt (20 mg/kg per day). Vehicle (10% DMSO in polyethylene glycol 400) is used in control mice. Quantification of tumour burden is by Bio-luminescent imaging (BLI), performed using an IVIS Spectrum Xenogen instrument and analysed using Living Image software v.2.50.

[1]. Silberstein SD, et al. Tonabersat, a gap-junction modulator: efficacy and safety in two randomized, placebo-controlled, dose-ranging studies of acute migraine. Cephalalgia. 2009 Nov;29 Suppl 2:17-27.

[2]. Chen Q, et al. Carcinoma-astrocyte gap junctions promote brain metastasis by cGAMP transfer. Nature. 2016 May 18;533(7604):493-8.

[3]. Kim Y, et al. Tonabersat Prevents Inflammatory Damage in the Central Nervous System by Blocking Connexin43 Hemichannels. Neurotherapeutics. 2017 May 30.

GAP-134 (Hydrochloride) | GAP 27 acetate salt | GAP 26 trifluoroacetate salt