Central inhibition prevents the in vivo acute toxicity of harmine in mice

Abstract

Background: Harmine is a β-carboline alkaloid that displays antidepressant, antitumor and other pharmacological effects. However, the strong toxic effects limit its clinical application, and should be first considered. Purpose: To evaluate the in vivo toxicity of harmine and explore intervention strategies against its toxicity. Methods: The in vivo toxicity of harmine was assessed from the symptoms, biochemical indices, and cardiovascular effects in mice. The intervention experiments were performed by using anesthetics, central drugs, and peripheral anticholinergics. Results: The acute toxicity of harmine is significantly dose-dependent and the median lethal dose is 26.9 mg/kg in vivo. The typical symptoms include convulsion, tremor, jumping, restlessness, ataxia, opisthotonos, and death; it also changes cardiovascular function. The anesthetics improved the survival rate and abolished the symptoms after harmine poisoning. Two central inhibitors, benzhexol and phenytoin sodium, uniformly improved the survival rates of mice poisoned with harmine. The peripheral anticholinergics didn’t show any effects. Conclusion: Harmine exposure leads to central neurological symptoms, cardiovascular effects and even death through direct inhibition of the central AChE activity, where the death primarily comes from central neurological symptoms and is cooperated by the secondary cardiovascular collapse. Central inhibition prevents the acute toxicity of harmine, and especially rapid gaseous anesthetics such as isoflurane, might have potential application in the treatment of harmine poisoning.