[Curare and its successors. A 50-year's evolution]

Area of Science:

• Anesthesiology and Pharmacology
• Drug Development and Discovery

Background:

• The introduction of curare in 1942 transformed anesthesia by enabling lighter general anesthesia levels and improving patient safety.
• Shortages and variability of curare spurred the development of synthetic analogues, focusing on bisquaternary ammonium compounds.

Discussion:

• Early synthetic agents like gallamine exhibited undesirable vagolytic effects, while succinylbischoline's depolarizing mechanism presented long-term disadvantages.
• Research focused on eliminating side effects such as histamine release, vagal, and ganglionic blockade seen with curare and other relaxants.

Key Insights:

• Improved understanding of structure-activity relationships, coupled with advanced analytical and electrophysiological methods, was crucial for developing safer muscle relaxants.
• Alcuronium and pancuronium emerged as non-depolarizing agents with reduced side effects compared to curare.
• The evolution of anesthesia techniques, including routine intubation and mechanical ventilation, highlighted the need for muscle relaxants with predictable pharmacokinetics and rapid recovery.

Outlook:

• Future muscle relaxant design should prioritize larger volumes of distribution and faster biodegradation.
• Development of adequate monitoring techniques is essential to manage and appreciate the recovery profiles of neuromuscular blocking agents.