Design, synthesis, and biological evaluation of new bis-benzylisoquinoline-based analogues as potential neuromuscular blocking agents.

Neuromuscular blocking agents (NMBAs) are widely used in anesthesia for intubation and surgical muscle relaxation. Novel atracurium and mivacurium derivatives were developed, with compounds 18c, 18d, and 29a showing mivacurium-like relaxation at 27.27 nmol/kg, and 15b, 15c, 15e, and 15h having a shorter duration at 272.7 nmol/kg. The structure-activity and configuration-activity relationships of these derivatives and 29a's binding to nicotinic acetylcholine receptors were analyzed through molecular docking. Rabbit trials showed 29a has a shorter duration compared to mivacurium. This suggests that linker properties, ammonium group substituents, and configuration are crucial for NMBA activity and duration, with compound 29a emerging as a potential ultra-short-acting NMBA.

Nuevos agentes relajantes musculares / New muscular relaxing agents

Desde los primeros extractos naturales curarinicos, hasta los analogos sinteticos aparecidos posteriormente, distintos farmacos han sido descritos como capaces de bloquear la transmision muscular. Aparte de la eficacia, todos estos farmacos presentan como denominador cumun efectos colaterales, generalmente como interferencia con el sistema nervioso autonomo, ademas de la desventaja de ser dependientes del higado y rinones para su metabolismo y eliminacion. Esto ha motivado a investigadores de la ultima decada, a realizar innovaciones en la estructura de los agentes bloqueadores no despolarizantes, tratando de obviar los inconvenientes que presentan los agentes ya conocidos, y poder brindar un manejo mas adecuado y seguro a los pacientes que requieren este tipo de medicacion..