Tiapride for the Treatment of REM Sleep Behaviour Disorder in Dementia with Lewy Bodies: A Case Series

Objective: REM sleep Behaviour Disorder (RBD) in Dementia with Lewy bodies (DLB) may be attributed to a decrease in dopaminergic neurotransmission. Thus, we studied the therapeutic efficacy of the pre and postsynaptic D2 and D3 receptor antagonist tiapride, which at a low dosage preferentially blocks presynaptic dopamine receptors and consequently leads to feedback activation of dopamine synthesis and to increased extracellular levels of dopamine. Methods: Six consecutive patients presenting at our memory clinic with RBD in DLB, in whom melatonin had been ineffective and clonazepam was found inappropriate for clinical reasons, were treated with triapride at dosages between 50 and 150 mg for twelve weeks. Results: Tiapride was well tolerated by all patients. Five of the six patients, reported was a decrease of the self-perceived frequency of bad dreams and the intensity and severity of motor and vocal enactments during sleep. In four of these six patients, this was also the case in the view of the patients’ bed partners. Conclusion: Tiapride may by an effective and well-tolerated treatment for RBD in patients with DLB.

Dopamine action in the nucleus accumbens

The action of dopamine was studied in the nucleus accumbens of acutely prepared rabbits. Dopamine was applied iontophoretically to those cells and cell populations that responded in a monosynaptic excitatory manner to ipsilateral fimbrial stimulation. This strategy was adopted to isolate the effects of dopamine on postsynaptic receptors thus avoiding the bias resulting from activation of presynaptic dopamine receptors on dopaminergic afferents. Dopamine was found to have a suppressive effect on the excitatory (N) component of the field response and on driven extracellular unitary discharges. The specificity of dopamine's effect with receptors was indicated by the facts that fluphenazine effectively antagonized dopamine's effect, whereas bicuculline did not. The effect of dopamine was dependent on the rate of fimbrial stimulation. Dopamine has a marked suppressive effect on the fimbria-induced response at 0.5 Hz of stimulation but not at 6.0 Hz. This frequency specificity could not be linked directly to a cyclic adenosine 3',5'-cyclic monophosphate (cyclic AMP) mechanism because the iontophoresis cyclic AMP and dibutyryl cyclic AMP had suppressive effects at both 0.5 and 6.0 Hz rates of stimulation. It is suggested that dopamine acts in the nucleus accumbens to increase the "signal-to-noise" ratio. This might be a form of "contrast enhancement" of an incoming hippocampal message.