Pharmacology of BOTOX(R) (Botulinum toxin type A) purified neurotoxin complex: Local versus systemic muscle activity measurements in mice

The local pharmacological effect of BOTOX(R) (Botulinum toxin type A) purified neurotoxin complex was evaluated after a single intramuscular injection in mice. Varying doses of BOTOX(R) were injected into the right gastrocnemius muscle. Repeated measures of muscle activity were used to determine the local and systemic effects of BOTOX(R) At the conclusion of each study, leg weights were recorded to collect data on the dose-response and time course of BOTOX(R)-induced muscle atrophy. A single intramuscular injection of BOTOX(R) reduced muscle strength in mice, measured as power of movement by the tail-suspension test (TST-power) and muscle atrophy in a dose-related manner. TST-power was reduced by 15 +/- 14 (3), 40 +/- 11 (3), 77 +/- 12 (4), 93 (2); mean +/- SEM (n) percent inhibition for doses 1, 10, 30 and 50 units/kg, respectively. Local effects were measured as a reduction in TST-power without any measurable effect on the immobility time (TST-immobility) or activity meter. Systemic muscle weakness was observed at doses greater than 30 units/kg with the TST-immobility. The activity meter counts were reduced with BOTOX(R) doses starting at 10 units/kg. Thus, these studies in mice have demonstrated a dose-related separation of a local muscle weakness from systemic muscle weakness of a single intramuscular injection of BOTOX(R).