In vitro effects of acetyl-DL-leucine (tanganil (R)) on central vestibularneurons and vestibulo-ocular networks of the guinea-pig

For 40 years, the amino acid acetyl-DL-leucine (or isoleucine/Tanganil(R)) has been used in clinical practice to reduce the imbalance and autonomic si gns associated with acute vertigo crises. In animal models, acetyl-DL-leuci ne was shown to accelerate vestibular compensation following unilateral lab yrinthectomy, while having only minor effects on normal vestibular function . However, the underlying mechanisms are unknown. In this study, the effect of acetyl-DL-leucine on the activity of central vestibular neurons of the medial vestibular nucleus (MVN) and/or the overall activity of vestibular-r elated networks was electrophysiologically measured in brainstem slices and in the isolated, in vitro whole brain (IWB) of guinea-pig. Only moderate e ffects were obtained in normal animals, where both excitatory and inhibitor y actions of acetyl-DL-leucine were obtained. However, intracellular record ings from MVN neurons revealed that the nature of the response depended on the resting membrane potential. The neurons excited by acetyl-DL-leucine we re significantly hyperpolarized compared to nonsensitive cells, whereas the neurons inhibited by this compound tended to display higher than normal me mbrane potentials. In accordance with these data, acetyl-DL-leucine reduced the prominent asymmetry characterizing the vestibular-related networks of IWBs taken from previously labyrinthectomized animals, by decreasing the ac tivity of the abnormally depolarized neurons on the hyperactive side. Altog ether, our results suggest that acetyl-DL-leucine might act mainly on abnor mally hyperpolarized and/or depolarized MVN neurons, by bringing back their membrane potential towards a mean value of -65 to -60 mV. Since in animal models, acute vestibular disorders are associated with asymmetrical spontan eous activities of MVN neurons, this study suggests how acetyl-DL-leucine m ay reduce acute, vestibular-related imbalances in humans.