agn-191659 and Hypoxia

Involvement of hormonal response (catecholamine release) to acute hypoxia induced by radioprotectors in modification of their radioprotective properties was studied in experiments on outbred mature female albino mice, female albino rats, and dogs of both sexes. The response intensity was evaluated by the reduction of radioprotective and toxic properties of indralin (a α1-adrenoceptor agonist and a radioprotector). The radioprotective effect of indralin was measured using lethal doses of whole-body γ-irradiation ((60)Co) and its acute toxicity was assessed by LD50. It was found that repeated administration of indralin with 30-60-min intervals was followed by weakening of its radioprotective effect. Similar sensitization effect of indralin was observed after pretreatment with cystamine and epinephrine. Comparison of the severity of sensitization after administration of epinephrine and cystamine in the dose providing radioprotective effect showed that the potential aminothiol-induced release of catecholamines can provide optimal long-term radioprotective effect of epinephrine.

Topics: 5-Methoxytryptamine; Adrenergic alpha-1 Receptor Agonists; Animals; Animals, Outbred Strains; Cystamine; Dogs; Drug Administration Schedule; Epinephrine; Female; Hypoxia; Injections, Intramuscular; Injections, Intraperitoneal; Lethal Dose 50; Male; Mice; Phenols; Radiation Injuries, Experimental; Radiation-Protective Agents; Rats; Receptors, Adrenergic, alpha-1; Survival Analysis; Whole-Body Irradiation