ABSTRACT
I. Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 373 A. Characteristics of Botulinum Neurotoxin (BoNT) Intoxication . . . . . . . . 375 B. Symptomology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 375 C. Functional Domains of BoNT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 376
II. Manifestations of Botulism. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 377 A. Foodborne Botulism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 377 B. Wound Botulism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 378 C. Infant Botulism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 378
III. Treatment Options. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 379 A. Pharmacological Intervention . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 380
1. Potassium Channel Blockers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 380 2. Specific Strategies for Therapeutic Intervention . . . . . . . . . . . . . . . . . 382
a. Inhibitors of Binding . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 382 b. Inhibitors of Internalization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 383 c. Inhibitors of Metalloprotease Activity. . . . . . . . . . . . . . . . . . . . . . . 384
IV. Conclusions and Future Research. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 386 Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 387 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 387
The botulinum neurotoxins (BoNTs)** comprise a family of seven distinct neurotoxic proteins (A-G) produced by immunologically discrete strains of the anaerobic bacterium, Clostridium botulinum.1,2 These toxins act on peripheral cholinergic
synapses to inhibit spontaneous and impulse-dependent release of acetycholine (ACh).3,4 Intoxication by BoNT results in muscle weakness, which can be fatal when the diaphragm and intercostal muscles become sufficiently compromised to impair ventilation.5 BoNTs are the most potent substances in nature and ingestion of as little as 1 ng/kg is sufficient to cause human lethality.6
