Long-acting neuromuscular blocks followed by rapid reversal may provide prolonged surgeries with improved conditions by omitting repetitive or continuous administration of the neuromuscular blocking agent (NMBA), eliminating residual neuromuscular block and minimizing postoperative recovery, which, however, is not clinically available. Here, we demonstrate that imidazolium-based macrocycles (IMCs) and acyclic cucurbit-[n]urils (ACBs) can form such partners by functioning as longacting NMBAs and rapid reversal agents through a pseudo[2]catenation mechanism based on stable complexation with K a values of over 10 9 M −1 . In vivo experiments with rats reveal that, at the dose of 2-and 3-fold ED 90 , one IMC attains a duration of action corresponding to 158 or 442 min for human adults, covering most of prolonged surgeries. The block can be reversed by one ACB with recovery time significantly shorter than that achieved by sugammadex for reversing the block of rocuronium, the clinically most widely used intermediate-acting NMBA.