The pharmacology of a new short-acting, non-depolarising muscle relaxant steroid (RGH-4201).
The actions of a new steroid 3alpha-pyrrolidino-17alpha-methyl-17alpha-aza-D-homo-5alpha-androstane-dimethobromide (RGH-4201) have been studied on the skeletal muscle, autonomic and cardiovascular systems in the conscious dog and in the anaesthetized cat and dog. In the cat and dog RGH-4201 exhibited a potent, non-depolarizing neuromuscular blocking action that was rapid in onset and of short duration. RGH-4201 was equipotent with suxamethonium and chandonium as a neuromuscular blocking agent in the conscious dog but was 2-3 times less active in the anaesthetized cat. Paralysis in the conscious dog was rapid in onset and of shorter duration than that of suxamethonium and chandonium. In the anaesthetized cat onset and duration of action was shorter than that of suxamethonium and chandonium. The neuromuscular block produced by RGH-4201 was rapidly and completely reversed by neostigmine releasing actions were observed. RGH-4201 has a cardiovagolytic activity similar to that of chandonium and diadonium. In open-chest dog, neuromuscular paralysing dose of RGH-4201 did not cause haemodynamic changes. Duration of action of a medium-term neuromuscular blocking agent (pipecurium bromide) was not affected by a preliminary dose of RGH-4201. Pathological alterations were not found in conscious beagle dogs treated daily for 14 days with 100 and 500 microgram . kg-1 of RGH-4201, however, a transient elevation on heart rate occurred during the paralysis.
D015113:Androstane-3,17-diol / Q000031:analogs & derivatives / Q000494:pharmacology; D000731:Androstanes / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D002415:Cats; D004285:Dogs; D004347:Drug Interactions; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006636:Histamine Release / Q000187:drug effects; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009469:Neuromuscular Junction / Q000187:drug effects; D003473:Neuromuscular Nondepolarizing Agents / Q000494:pharmacology* / Q000633:toxicity; D017300:Pipecuronium; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D009435:Synaptic Transmission / Q000187:drug effects
D000731:Androstanes; D003473:Neuromuscular Nondepolarizing Agents; D010879:Piperazines; D017300:Pipecuronium; D015113:Androstane-3,17-diol; C021177:dihydrochandonium