Rovatirelin (S-0373) is a novel, synthetic and non-peptide mimetic of thyrotropin-releasing hormone (TRH) being developed by Kissei Pharmaceutical for the treatment of spinocerebellar degeneration. Rovatirelin binds to the human TRH receptor with higher affinity (Ki=702nM) than taltirelin (Ki=3877nM). Rovatirelin increased the spontaneous firing of action potentials in the acutely isolated noradrenergic neurons of rat locus coeruleus (LC). Rovatirelin increased locomotor activity. Rovatirelin may have an orally effective therapeutic potential in patients with SCD.