title: Investigation of acute cardiovascular and respiratory toxicity of HLö 7 dimethanesulfonate and HI 6 dichloride in anaesthetized guinea-pigs.
abstract: The bis-pyridinium dioxime HLö 7 is considered to possess promising therapeutic properties in the treatment of organophosphate poisoning. Acute circulatory and respiratory effects of HLö 7 and HI 6 were therefore compared in anaesthetized guinea-pigs. Female Pirbright white guinea-pigs were anaesthetized with urethane and the carotid artery, jugular vein and trachea were cannulated. Saline or atropine, 10 mg/kg, or HLö 7 or HI 6 (30 or 100 mumol/kg, each) or atropine plus oxime were injected intravenously after base line measurements. Respiratory and circulatory parameters were recorded for 60 min., then blood was drawn for AChE measurement. Injection of HLö 7 or HI 6 alone resulted in a temporary, dose-dependent hypotension, an almost unchanged heart rate and a slight respiratory stimulation. A more severe hypotension appeared after the administration of atropine plus HLö 7 or HI 6. In these groups heart rate and respiration were markedly stimulated. Measurement of AChE activity in blood samples revealed no impairment by HLö 7 or HI 6 with or without atropine. These results suggest that HLö 7 has only transient effects on the cardiorespiratory system after intravenous administration and its safety regarding acute circulatory and respiratory toxicity is comparable to HI 6.
authors.affiliation: Institute of Pharmacology and Toxicology, Federal Armed Forces Medical Academy, Garching, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Worek
authors.forename: L
authors.initials: L
authors.lastname: Szinicz
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000758:Anesthesia; D000818:Animals; D001285:Atropine / Q000633:toxicity; D001794:Blood Pressure / Q000187:drug effects; D002318:Cardiovascular Diseases / Q000139:chemically induced*; D002319:Cardiovascular System / Q000187:drug effects; D002801:Cholinesterase Reactivators / Q000633:toxicity*; D005260:Female; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D010091:Oximes; D011725:Pyridines / Q000633:toxicity*; D011726:Pyridinium Compounds / Q000633:toxicity*; D012120:Respiration Disorders / Q000139:chemically induced*; D012137:Respiratory System / Q000187:drug effects
chemical_list: D002801:Cholinesterase Reactivators; D010091:Oximes; D011725:Pyridines; D011726:Pyridinium Compounds; C058577:HLo 7; D001285:Atropine; D000110:Acetylcholinesterase; C022870:asoxime chloride