Modulation of monomethylhydrazine-induced seizures by ivermectin

Exposure to monomethylhydrazine (MMH), a common rocket propellant, can cause dose-related central nervous system (CNS) disturbances ranging from tremors to tonic-clonic convulsions to death. MMH inhibits gamma-aminobutyric acid (GABA) synthesis in the CNS. Diazepam (BZ) acts at the GABA receptor site, and it is also here that ivermectin (AVM) is pharmacologically active. Mice were injected with 30 mg/kg MMH. Groups of 12 mice each were then given varying doses of AVM (5, 10 and 15 mg/kg), or AVM + BZ combinations (5 mg/kg AVM with 5 mg/kg BZ, 10 mg/kg AVM with 5 mg/kg BZ). Time to first convulsion and time to death were recorded over the next 7 h and all groups were monitored over the next 7 days. Times to convulsion were not altered with AVM alone, but death was significantly prevented with AVM dosages. A treatment of 10 mg/kg AVM with 5 mg/kg BZ resulted in no seizures or deaths.