Some New Neuromuscular Blocking Agents

Development of ultra short‐acting muscle relaxant agents: History, research strategies, and challenges

“…Bis (N,N 0 -dimethyl piperidinium) 1-12 dodecamethane represented one of the first, better explored bis-piperidinium derivatives; 2 and the elongated 1-16 diammonium agent: prestonal, which underwent clinical trial has been one of the first short acting depolarizingnondepolarizing agent, 26 but it did not survive beyond that stage. Subsequently Bovet (1972) 25 reviewed other short acting NMB agents and listed: (a) oxalolaudonium 27 (Table I) closely related to laudexium, one of the first successful synthetic tetrahydroisoquinoline-type agents, although with a long duration of action. In oxalolaudonium the decamethylene linker has been replaced by an ''equidistant'' dipropyl oxalate linker, resulting in short duration action profile.…”

“…The role of rapid ester hydrolysis in the pharmacokinetics of NMB agents was explored first by Bovet et al (1949) 1 and Brücke (1956) 33 with different choline diesters. Hydrolysis of diester linkers has been applied by Nador (1953, 1957) 6,7 and Haining et al (1960) 34 in the development of bis tropinium diesters and by Collier et al (1958) 27 who described the first diester type tetrahydroisoquinolines. Agents with the above listed structural elements, found first in the fifties and sixties and exploited later as lead compounds, were recognized up to recently, as the ''mainstream'' lead compounds for the design of new, short acting NMB agents.…”

The Quest for a Short‐Acting Nondepolarizing Neuromuscular Blocking Agent

“…A series of laudanosinium esters reported by COLLIER et al (1958) and BRITTAIN et al (1961) is represented by y-oxalolaudonium bromide ( Fig. l), whose duration of action in the cat was half that of succinylcholine.…”