title: Summary of safety tests with pipecurium bromide, a new neuromuscular blocking agent.
abstract: Acute toxicity studies with 2 beta,16 beta-bis(4'-dimethyl-1'-piperazino)-3 alpha,17 beta-diacetoxy-5 alpha-androstane dibromide (pipecurium bromide, RGH-1106, Arduan), a new neuromuscular blocking agent, revealed an order of sensitivity as follows: rabbits greater than mice greater than rats. Subchronic toxicity was tested on conscious dogs by 20 daily doses of 150 microgram/kg i.v. corresponding to 4-fold the planned clinical dose followed by daily intubation and artificial ventilation until recovery of spontaneous respiration. Dosage was limited by prolonged paralysis time requiring artificial ventilation. Apart from daily stress of paralysis preceding intubation no irreversible toxic changes were detected by laboratory and morphological tests. ECG changes were restricted to paralysis time, they were characterized by transitory arrhythmia and variation of the ST-segment. In additional studies on conscious and unconscious dogs no lethal ECG changes could be induced with cumulative dose totalling 10 mg/kg i.v. Short-term in vivo and in vitro mutagen tests did not reveal either mutagenic and clastogenic effects or increase of chromosomal aberrations. Intravenous local tolerance in rats was satisfactory.
mesh_terms: D015113:Androstane-3,17-diol / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000633:toxicity*; D000732:Androstanols / Q000633:toxicity*; D000818:Animals; D004285:Dogs; D004562:Electrocardiography; D005260:Female; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D009153:Mutagens; D009466:Neuromuscular Blocking Agents / Q000008:administration & dosage / Q000633:toxicity*; D017300:Pipecuronium; D010879:Piperazines / Q000008:administration & dosage / Q000633:toxicity*; D011247:Pregnancy; D011817:Rabbits; D051381:Rats; D012867:Skin / Q000187:drug effects; D013045:Species Specificity; D013997:Time Factors
chemical_list: D000732:Androstanols; D009153:Mutagens; D009466:Neuromuscular Blocking Agents; D010879:Piperazines; D017300:Pipecuronium; D015113:Androstane-3,17-diol