Effect of 3,4-diaminopyridine on the survival of mice injected with botulinum neurotoxin type A, B, E, or F.
To determine the efficacy of 3,4-diaminopyridine (3,4-DAP) as a potential treatment for botulism, its effect on the survival times of mice injected with type A, B, E, or F botulinum toxin (Bo Tx) was examined. Mice were injected ip with 10, 20, or 40 LD50 of Bo Tx. Three hours later, when the mice displayed signs of botulism, half of each group of mice was treated with 3,4-DAP, an agent which increases nerve-evoked transmitter release. At each dose of type A Bo Tx tested, 3,4-DAP definitely prolonged survival. In contrast, treatment with the drug did not significantly increase the survival time of mice injected with type B, E, or F Bo Tx. The differences in efficacy of 3,4-DAP against the four serotypes of Bo Tx together with previously reported variations in specific toxicity and duration of paralysis may reflect differences in the pharmacological activity of these neurotoxins.
D015761:4-Aminopyridine / Q000031:analogs & derivatives*; D000077770:Amifampridine; D000631:Aminopyridines / Q000627:therapeutic use*; D000818:Animals; D001905:Botulinum Toxins / Q000037:antagonists & inhibitors; D001906:Botulism / Q000188:drug therapy*; D007274:Injections, Intraperitoneal; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D012703:Serotyping; D013997:Time Factors
D000631:Aminopyridines; D015761:4-Aminopyridine; D001905:Botulinum Toxins; D000077770:Amifampridine