Conformation, action, and mechanism of action of neuromuscular blocking muscle relaxants

Goodbye Suxamethonium!

“…In other words, each half-molecule of suxamethonium acts like one acetylcholine, and each molecule of suxamethonium uses only one of its two half-molecules at a time [10,11]. This contradicts the traditional belief that suxamethonium works like decamethonium, with a bisquaternary mechanism of action.…”

“…The monoquaternary mechanism of action of suxamethonium is interesting from the viewpoint of modern receptor theory and molecular conformation-action relationship [11]. First, vecuronium proves that monoquaternary muscle relaxants could be better than their bisquaternary analogues [8].…”

“…First, vecuronium proves that monoquaternary muscle relaxants could be better than their bisquaternary analogues [8]. Then, basic thermodynamic calculations show that suxamethonium cannot exist as a straight molecule [11]. The negatively charged oxygen atoms are strongly attracted to the positively charged ammonium heads, and the energy penalty in existing as a straight molecule is too high.…”

“…The negatively charged oxygen atoms are strongly attracted to the positively charged ammonium heads, and the energy penalty in existing as a straight molecule is too high. In other words, suxamethonium is too short to reach both receptive sites simultaneously [11] (Fig. 1).…”

“…Lee [11] recently proposed a general mechanism of action of the NMBs based on their molecular conformation. As a molecule constantly vibrates around each rotatable bond to seek the lowest possible total energy, it preferentially populates the lowest energy conformations.…”