Reversing neuromuscular blocking agent decamethonium by carboxylatopillar[6]arene based on host-guest encapsulation

Neuromuscular blocking agents (NMBAs) are extensively used during anesthesia to improve surgical conditions by relaxing skeletal muscle movements. Rapid neuromuscular recovery after surgery is desirable to facilitate the recovery of muscle function and prevent residual blockade. Decamethonium (C10) is a classic NMBA, which has been restricted over the past decades ascribed to lack of a suitable antidote in clinic. Herein we used carboxylatopillar[6]arene (CP6A) to reverse neuromuscular blocker effect of C10 through direct host-guest encapsulation. NMR and isothermal titration calorimetry served to confirm the complexation between CP6A and C10 with robust affinity [(1.07 ± 0.14) × 107 L/mol]. The CP6A was further used as a reversal agent of C10, which facilitated to decrease C10 concentration in mice blood and excrete via urinary clearance, resulting in rapid recovery from muscle relaxation. These favorable outcomes might lead us to suggest that this supramolecular strategy could allow patients to regain lucidity much faster than spontaneous recovery from anesthesia. Reversal of neuromuscular blocker effect of decamethonium (C10), by carboxylatopillar[6]arene (CP6A) via direct host-guest encapsulation is reported. The efficient encapsulation by CP6A with a Ka value about 107 L/mol, facilitate to decrease C10 concentration in mice blood via urinary clearance, resulting in rapid recovery from muscle relaxation. [Display omitted]