Efficacy of 3,4-Diaminopyridine as a Therapy for Type C Botulism
ARMY MEDICAL RESEARCH INST OF INFECTIOUS DISEASES FORT DETRICK MD PATHOLOGY DIV
Pagination or Media Count:
Botulism is caused solely by the protein neurotoxins produced by Clostridium botulinum. These toxins act by inhibiting acetylcholine release at neuromuscular junctions. Agents which stimulate the efflux of neutrotransmitter, such as 3,4-diaminopyridine 93,4-DAP, could be useful in the treatment of botulism. Type C botulism affects a variety of species, but is especially severe in waterfowl, causing massive die-offs each year. To evaluate 3,4-DAP as a potential therapy for type C botulism, mice were injected i.p. with 10, 20 or 40 LD50 of type C toxin. After 3 hr, when symptoms of botulism were apparent, therapy with 3,4-DAP was begun for half of each group of mice. Mice were injected i.p. with 8 mgkg of the drug hourly. This treatment with 3,4-DAP did not significantly increase the survival times of mice receiving type C toxin. However, therapy with 3,4-DAP, administered at the same concentration and according to the same dosage schedule, significantly prolonged the survival times of mice that had received 20 LD50 of type A botulinum neurotoxin. This difference in the effectiveness of 3,4-DAP against type A and C botulinum toxins may be due to variations in the mechanism of action of these neurotoxins at the molecular level.
- Medicine and Medical Research