The Toxic Study Of Harmine In Mice

Objective:To evaluate the in vivo toxicity of harmine,as well as to explore potential intervention strategies against harmine toxicity in intact mice.Methods:The in vivo toxicity of harmine was assessed from the aspects of clinical manifestations,biochemical indices,and cardiovascular effects in intact mice,whereas the intervention experiments were performed using a series of neurological drugs including anesthetics,central drugs,and peripheral anticholinergics.Results:The in vivo acute toxicity of harmine is significantly dose-dependent,where the LD₅₀ is 26.9 mg/kg,i.v.,and the typical symptoms include convulsions,tremors,jumps,restlessness,ataxia,opisthotonos,and death.Harmine also increases the myocardial enzymes,causes the collapse of blood pressure,decreases the heart rate and changes the ECG waves.Three different types of anesthetics,urethane,chloral hydrate and isoflurane uniformly improved the survival rate as well as abolished the neurological symptoms after harmine poisoning;in contrast,they had a much weaker effect on DDVP poisoning.Two central inhibitors,benzhexol hydrochloride and phenytoin sodium,uniformly improved the survival rates of mice poisoned with harmine and DDVP.The M-type anticholinergic agent atropine,the N-type agent atracurium and the ACh E reactivator drug pralidoxime chloride did not show any effect on either the survival rate or the neurological symptoms of harmine poisoning.Conclusion:Harmine leads to acute central neurological symptoms,cardiovascular effects and death in intact mice,which may be related to the influence of harmine on central ACh E activity.Central inhibition prevents against the acute toxicity of harmine whereas anesthetics,especially the rapid gaseous anesthetics such as isoflurane,might have potential applications in the treatment of harmine poisoning.