Atracurium Besylate

Atracurium besylate was administered by continuous intravenous infusion to ten children following orthotopic liver transplantation, with a mean duration of 36.9 hours and maximum infusion rate of 1.44 mg kg⁻¹ h⁻¹. Neuromuscular block was monitored using train-of-four accelerometry. The mean terminal half-life of atracurium was 18.8 minutes, steady-state plasma clearance was 13.9 ml min⁻¹ kg⁻¹, and volume of distribution was 390 ml kg⁻¹, all higher than values reported in adults after successful liver transplantation. Mean recovery time to a train-of-four ratio greater than 0.75 after stopping the infusion was 23.6 minutes. The study concluded that atracurium is an effective and safe neuromuscular blocking agent in critically ill children after liver transplantation, relying on organ-independent Hofmann elimination, and laudanosine concentrations remain within non-toxic limits when graft function is satisfactory.

Fig. 1 Plasma concentrations of Atracurium for a typical patient. (Chow B.; et al. 2000)

Atracurium besylate was identified as a small molecule that effectively induces astroglial differentiation of patient-derived glioblastoma stem cells without affecting neuronal differentiation. The mechanism involves antagonism of nicotinic acetylcholine receptors, as the nAChR agonist DMPP significantly blocked its pro-differentiation activity. Atracurium treatment significantly reduced the clonogenic capacity of GSC neurosphere lines in a largely irreversible manner. Ex vivo pre-treatment of GSCs expressing CHRNA1 and CHRNA9 with atracurium increased the survival of xenotransplanted mice, suggesting depletion of tumor-initiating subpopulations. This study revealed a previously unrecognized anti-cancer mechanism of atracurium besylate.

Fig. 2 Atracurium Besylate inhibits tumor engraftment in vivo. (Spina R.; et al. 2015)