[Investigation of neuromuscular blocking agents at Richter Ltd].
Investigation of new neuromuscular blocking agents was started 30 years ago in Richter Ltd. This paper presents the results obtained by Richter's scientists. 2 compounds out of 100 bisquaternary ammonio steroid having androstane skeleton were selected for further pharmacological study. One of these agents, pipecuronium bromide (Arduan) elicited long-lasting block of neuromuscular transmission without cardiovascular side effects in both animal experiments and clinical studies. Arduan is a powerful competitive antagonist of acetylcholine, since it can bind pre- and postsynaptic (N1) receptors of the transmitters. It has no remarkable cumulative effect. Neostigmine rapidly and completely antagonized the neuromuscular blockade caused by pipecuronium. Arduan was introduced into clinical practice. The second compound, RGH-4201 (Duador) evoked a neuromuscular block of short duration. It showed slight atropin-like cardio-vagolytic effect in animal experiments. In the clinical studies, however, the cardiovascular side effects were found to be too strong. Therefore, it was not introduced in clinical practice.
Kárpáti
Egon
E
Richter Gedeon Vegyészeti Gyár Rt., Budapest.
Bíró
Katalin
K
Kukorelli
Tibor
T
D000731:Androstanes / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D004345:Drug Industry; D006801:Humans; D006814:Hungary; D009466:Neuromuscular Blocking Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D017300:Pipecuronium / Q000494:pharmacology / Q000627:therapeutic use; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology / Q000627:therapeutic use; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D000731:Androstanes; D009466:Neuromuscular Blocking Agents; D000644:Quaternary Ammonium Compounds; D017300:Pipecuronium; C021177:dihydrochandonium