Influence of repeated doses on accumulation of ibogaine and noribogaine in organs of mice

Abstract

Extracts of Tabernanthe Iboga (Apocynaceae) have been used as CNS stimulants at low doses or as hallucinogens at high doses. Ibogaine reduces craving for cocaine and morphine, attenuates morphine withdrawal symptoms [1]. Ibogaines metabolite noribogaine is pharmacologically active and produces effects that mimic those of ibogaine [2]. We evaluated the influence of repeated doses on the accumulation of ibogaine and noribogaine in organs of mice. Material and methods. Ibogaine and noribogaine were administered intragastrically to white laboratory mice via a stomach tube. 0.5 LD50 concentration of ibogaine (131 mg/kg) and noribogaine (315 mg/kg) [4] were used for determination of concentrations in organs of mice 24 h after single dose, and 0.05 LD50 ibogaine (13.15 mg/kg) and 0.05 LD50 noribogaine (31.5 mg/kg) - to determine the influence of repeated doses on accumulation in organs of mice. Control animals received the same volume of saline. Concentrations of ibogaine and noribogaine were determined by HPLC. Results. After 24 hours the maximum ibogaine concentration was determined in the spleen, kidney and heart tissue. After 14 days of repeated ibogaine doses, the same tendency of ibogaine concentrations in mice organs was observed. However, after 14 days, the maximum ibogaine concentration was established in the heart (Fig.1). It allows for the confirmation of the statement found in literature sources that ibogaine has an impact on cardiovascular system [3,5]. 24 hours after single noribogaine dose, the maximum concentrations were determined in mice spleen, heart and kidney samples. After 14 days of repeated noribogaine doses, the maximum concentration was also established in spleen samples. However, a different tendency was observed in other tested organs (Fig.2). The tendency of increase of noribogaine concentrations in brain tissues allows for the assumption that the repeated usage of noribogaine can lead...[...].