Bradanicline tosylate

Bradanicline (TC-5619) tosylate is an oral agonist of the α7nAChR with moderate penetration of the blood-brain barrier. It demonstrates high affinity and subtype selectivity for the human α7nAChR. This compound exhibits antitussive activity, dependent on sustained receptor binding and activation. Systemic administration of Bradanicline tosylate enables dose-dependent inhibition of cough induced by citric acid, bradykinin, and inhaled nicotine. In preclinical studies, Bradanicline tosylate has shown good tolerance and is commonly used in research related to chronic refractory cough.

Bradanicline tosylate potently and selectively activates human α7 nAChRs in vitro, with an EC50 of 17 nM. It does not induce desensitization of α7 nAChRs in vitro.

Bradanicline tosylate, administered orally at doses ranging from 3 to 100 mg/kg, 60 minutes prior to induction, demonstrates a dose-dependent suppression of citric acid-induced cough in male Hartley guinea pigs, with statistically significant effects at 10, 30, and 100 mg/kg. Additionally, when injected intraperitoneally at 30 mg/kg, 30 minutes before induction, it effectively inhibits citric acid-induced cough in the same model, though no effect is observed when the compound is delivered to the airways via aerosol at a concentration of 3 mg/mL alongside citric acid. Furthermore, bradanicline tosylate at a dose of 30 mg/kg, administered via intraperitoneal injection 30 minutes before exposure, effectively reduces bradykinin-induced cough in male Hartley guinea pigs. Similarly, the compound at the same dosage and administration method suppresses nicotine-induced cough in this animal model.