INTRACEREBRALLY INJECTED TREMORIGENIC INDOLE ALKALOIDS

Summary-The indole alkaloids harmane, harmtne. ibogrine, iboxygaine and ibogahne. Recently we have shown that the tremor-producing power of some harmala and iboga alkaloids is much more influenced by chemical structure than by lipid solubility, which points to specific receptors for indole compounds in tremorigenic brain structures (ZETLER, SINOBARTL and SCHLOSSER, 1972; SINGBARTL,~ETLER and SCHLOSSER, 1972). Tremorigenic activity was considerably enhanced by the introduction of a methoxy group into the indole ’ nucleus. In the same study, harmalol caused tremor in mice only after intracerebral but not after intravenous application. The reason for this discrepancy is the very low lipid solubility which prevented this compound, after iv. injection, from reaching brain concentra-: overcoming imnortant Dharmacokinetic obstacles which perhaps prevented the indole rom causing tremor in mice after subcutaneous injection (ZETLER, 1964). This inactivity is in strong contrast to the tremori-genie activity of the closely related alkaloids ibogaine, iboxygaine, and ibogaline. It was therefore necessary to elucidate, with the aid of intracerebral application, whether (a) the alkaloids just mentioned are in fact devoid of tremorigenic power, and (b) the importance it, too. These points are obviously ltors for the indole structures in 6 METHODS a Animals a Male albino mice, 22-27 g in weight and of the NMRI-strain, were bought from R. BIumler (Wolfratshausen) and kept in groups of 25 at an ambient temperature of 23°C. The experiments were performed in the same room at the same temperature. Each animal was used only once and had free access to food (Altromin pellets) and tap water