Study of the Acute Toxic Effects, Metabolssm and Pharmacological Activity of the Organic NF Compounds Designated NFPA, TVOPA, PEG, and R

摘要

This investigation was conducted to explore the acute toxic and pharmacological properties of certain organic NF compounds designated as NFPA, TVOPA, R, and PFG. Toxicity was evaluated in rats and mice by the inhalation, intraperitoneal, and intragastric routes of administration. The intraperitoneal LD50's in rats were 25, 215, 140, 155 mg/kg for NFPA, TVOPA, R, and PFG respectively. There was little interspecies difference in toxicity. However, intragastric administration was uniformly less toxic except for compound PFG, which demonstrated approximately the same level of toxicity by both intraperitoneal and intragastric route. Excretion of fluoride after administration of NFPA, TVOPA, or sodium fluoride accounted for approximately 15-30% of the administered compound. Pharmacological studies in anesthetized dogs demonstrated respiratory, cardiovascular, and hemodynamic changes after NFPA and TVOPA. Hypertension, tachycardia, and hyperpnea were observed immediately after administration followed by hypotension, increased hematocrit, and continued tachycardia and hyperpnea. Pretreatment with phenoxybenzamine blocked the pressor response; bilateral vagotomy eliminated the respiratory effects.