Synthesis and structure-activity relationships of neuromuscular blocking agents.
The first use of neuromuscular blocking agents (muscle relaxants) in clinical practice (1942) revolutionised the practice of anaesthesia and started the modern era of surgery. Since 1942 introduction of tubocurarine (18) neuromuscular blocking agents have been used routinely to provide skeletal muscle relaxation during surgical procedures allowing access to body cavities without hindrance from voluntary or reflex muscle movement. After the introduction of tubocurarine and the depolarizing suxamethonium chloride (4) (1949) several nondepolarizing steroidal and nonsteroidal neuromuscular blocking agents with different onset time and duration of effect were introduced e.g. gallamine triethiodide (1) (1949), methocurine (2) (1949), alcuronium chloride (3) (1963), pancuronium bromide (9) (1968), vecuronium bromide (11) (1982), pipecuronium bromide (10) (1982), atracurium besylate (5) (1982), doxacurium chloride (6) (1991), mivacurium chloride (8) (1992), rocuronium bromide (12) (1994) cisatracurium besylate (7) (1996), and rapacuronium bromide (13) (2000). SZ 1677 (14) a steroid type nondepolarizing neuromuscular blocking agent under development (preclinical phase). This review article deals with a comprehensive survey of the progress in chemical, pharmacological and, in some respects, of clinical studies of neuromuscular blocking agents used in the clinical practice and under development, including the synthesis, structure elucidation, pharmacological actions, structure activity relationships studies of steroidal and nonsteroidal derivatives.
Tuba
Zoltan
Z
Steroid Research Section, Chemical Works of Gedeon Richter Ltd.,10, POB 27, Budapest, H-1475, Hungary. s.maho@richter.hu
Maho
Sandor
S
Vizi
E Sylvester
ES
D000731:Androstanes / Q000737:chemistry / Q000494:pharmacology; D000732:Androstanols / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D001965:Bromides / Q000737:chemistry / Q000494:pharmacology; D003472:Curare / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology; D004355:Drug Stability; D007546:Isoquinolines / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D009466:Neuromuscular Blocking Agents / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D000077489:Piperazine; D010879:Piperazines / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013390:Succinylcholine / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology
C458501:1-(3-hydroxy-17-acetyloxy)-2-(1.4-dioxa-8-azaspiro-(4,5)-dec-8-yl)-(5alpha-androstane-16-yl)-1-(2-propenyl) pyrrolidine; D000731:Androstanes; D000732:Androstanols; D001965:Bromides; D007546:Isoquinolines; D009466:Neuromuscular Blocking Agents; D010879:Piperazines; D000077489:Piperazine; C062424:petaline; D003472:Curare; D013390:Succinylcholine