Abstract
To evaluate acute toxic effect of ibogaine and noribogaine on the survival of mice and determine median lethal doses of the substances mentioned. White laboratory mice were used for the experiments. Ibogaine and noribogaine were administered intragastrically to mice via a stomach tube. Control animals received the same volume of saline. The median lethal dose was calculated with the help of a standard formula. To determine the median lethal dose of ibogaine, the doses of 100, 300, 400, and 500 mg/kg were administered intragastrically to mice. The survival time of mice after the drug administration was recorded, as well as the number of survived mice in each group. Upon administration of ibogaine at a dose of 500 mg/kg, all mice in this dose group died. Three out of four mice died in the group, which received 300 mg/kg of ibogaine. No mouse deaths were observed in the group, which received 100 mg/kg of ibogaine. The determined LD(50) value of ibogaine equals to 263 mg/kg of body mass. In order to determine the median lethal dose of noribogaine, the doses of 300, 500, 700, and 900 mg/kg were administered to mice intragastrically. Noribogaine given at a dose of 500 mg/kg had no impact on the mouse survival. The increase of noribogaine dose to 700 mg/kg of mouse body mass led to the death of three out of four mice in the group. Upon administration of noribogaine at a dose of 900 mg/kg, all mice in this group died. The LD(50) value of noribogaine in mice determined on the basis of the number of dead mice and the size of the doses used equals to 630 mg/kg of mouse body mass. The behavior of mice was observed upon administration of ibogaine or noribogaine. Low doses of ibogaine and noribogaine had no impact on the mouse behavior. External effects (convulsions, nervous behaviour, limb paralysis) were observed only when substances were administrated at higher doses. It has been determined that the median lethal dose of ibogaine and noribogaine equals to 263 mg and 630 mg/kg of mouse body mass, respectively. The toxicity of ibogaine is 2.4 times higher than that of noribogaine.
Highlights
Looking for new medications for the treatment of drug and alcohol dependence encourages us to focus more attention on and investigate an indole alkaloid ibogaine
In order to determine the median lethal dose of noribogaine, the doses of 300, 500, 700, and 900 mg/kg were administered to mice intragastrically
Noribogaine given at a dose of 500 mg/kg had no impact on the mouse survival
Summary
Looking for new medications for the treatment of drug and alcohol dependence encourages us to focus more attention on and investigate an indole alkaloid ibogaine. There are findings demonstrating its capability to attenuate craving for alcohol [1]. An active metabolite of ibogaine, noribogaine, has been identified and is currently being analyzed. Occurring ibogaine is a psychoactive alkaloid extracted from the Tabernanthe iboga shrub. Preclinical studies have demonstrated that ibogaine reduces craving for cocaine and morphine, attenuates morphine withdrawal symptoms [3]. Based on the clinical studies, a conclusion can be made that ibogaine has a certain antiaddictive action [4]. The identified antagonistic activity of ibogaine on Nmethyl-D-aspartate receptors as well as its agonist activity on opioid receptors can be regarded as a possible mechanism of antiaddictive action [5]. Some of ibogaine actions can be attributed to its long-lasting metabolite, O-desmethyli-
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