Narrative Review of the Role of Nondepolarizing Neuromuscular Blocking Agents in Anesthesia: Perspective 2026.

In this narrative review, we summarize the current state of knowledge on novel isoquinolinium chlorofumarate diesters and pinnatoxins as potential neuromuscular blocking agents for modern anesthesia. Isoquinolinium derivatives gantacurium, CW002, CW011, and CW1759-50 are discussed due to promising initial findings, with animal and human studies presented to assess which agent may have the greatest potential for future clinical use. The approval process for gantacurium has reached Phase III clinical trials, but further trials are no longer ongoing. CW002 has undergone animal and human testing, and early results suggest fewer cardiovascular and pulmonary adverse effects; however, CW002 produces a longer neuromuscular block and is more difficult to antagonize than gantacurium. CW011 and CW1759-50 have been tested only in animal models. We also describe agents used to reverse neuromuscular block. L-cysteine is an amino acid that reverses the described fumarate-based neuromuscular blocking agents by reacting with the carbon-carbon double bond to form a stable thioether adduct that cannot bind to acetylcholine receptors. This adduct then slowly hydrolyses into inactive fragments, enabling rapid and complete reversal. Calabadion binds aminosteroid and benzylisoquinoline neuromuscular blockers by forming "host-guest" complexes, rapidly binding free relaxant molecules in plasma and acting faster than sugammadex, making it a potentially promising reversal agent. This article aims to review the role of nondepolarizing neuromuscular blocking agents in anesthesia.