The effectiveness of different isomers of octanol as blockers of harmaline-induced tremor

Abstract

Intracellular recording in the guinea-pig brainstem slice has demonstrated that high molecular weight alcohols block the low threshold calcium channel (LTCC) in the inferior olive (IO). These alcohols thus provide a tool for understanding the function of the pacemaking cellular networks of the olivo-cerebellar system, since the LTCC has been implicated in the oscillatory behavior of these neurons. Aspects of normal and pathological tremor are also believed to be mediated by these circuits, and thus development of effective ways of blocking the LTCC in vivo may eventually lead to novel treatments for essential tremor. The present experiments evaluated the effectiveness of the isomers of octanol in decreasing harmaline-induced tremor in vivo in the rat. Harmaline was used in this study because its tremorgenic action is mediated at the level of IO; octanol was found to be a potent antagonist of harmaline-induced tremor. Significant differences between the isomers further suggested conformational differences. This, taken in conjunction with the lack of effect of octanol in both IO lesioned rats and oxotremorine-induced tremor, implied that the action of the alcohol may be mediated at a specific binding site. These findings thus support the conclusions that the antagonism of harmaline-induced tremor by octanol occurs in the IO, and, in view of the previously reported in vitro data, that octanol may be an effective blocker of the LTCC in vivo.