Combined administration of anisodamine and neostigmine produces anti-shock effects: involvement of α7 nicotinic acetylcholine receptors

Aim: To evaluate the anti-effects of anisodamine and neostigmine in animal models of endotoxic and hemorrhagic shock. Methods: Kunming mice were injected with lipopolysaccharide (LPS 30 mg/kg, ip) to induce endotoxic shock. Anisodamine (12.5, 25, and 50 mg/kg, ip) and neostigmine (12.5, 25, and 50 mu g/kg, ip) were administered immediately after LPS injection. Survival rate was monitored, and the serum levels of TNF-alpha and IL-1 beta were analyzed using ELISA assays. The effects of anisodamine and neostigmine were also examined in alpha 7 nicotinic acetylcholine receptor (alpha 7 nAChR) knockout mice with endotoxic shock and in Beagle dogs with hemorrhagic shock. Results: In mice with experimental endotoxemia, combined administration of anisodamine and neostigmine significantly increased the survival rate and decreased the serum levels of inflammatory cytokines, as compared to those produced by either drug alone. The anti-shock effect of combined anisodamine and neostigmine was abolished in alpha 7 nAChR knockout mice. On the other,hand, intravenous injection of the combined anisodamine and neostigmine, or the selective alpha 7 nAChR agonist PNU282987 exerted similar anti-shock effects in dogs with hemorrhagic shock. Conclusion: The results demonstrate that combined administration of anisodamine and neostigmine produces significant anti-shock effects, which involves activation of alpha 7 nAChRs.