Levodopa-induced dyskinesia is a common problem in Parkinson's disease (PD). In particular,
targeting non-dopaminergic systems may be an option for reducing dyskinesia without worsening
motor symptoms. One such target may be histamine. The central histaminergic system is
involved in diverse biological functions including thermoregulation, eating, and sleep; a
role in motor activity is suggested by strong histaminergic innervation of the basal ganglia.
Histamine H2 receptors are highly expressed in the striatum, particularly on the GABAergic
striatal-pallidal and striatal-nigral pathways Histamine H2 stimulation modulates
acetylcholine release. Previous studies have demonstrated that blocking acetylcholine with
anticholinergic agents can induce chorea. The investigators propose that histamine H2
receptor stimulation decreases acetylcholine in the striatum and increases activity of the
direct striatal output pathway, a key component of the neural mechanisms underlying
dyskinesia.
The investigators hypothesise that H2 antagonists would reduce activity of the direct
striatopallidal pathway and so potentially reduce levodopa-induced chorea
Famotidine has also been assessed in schizophrenia in a small cases series to treat
schizophrenia, with tolerability. Clinical experience thus suggests the suitability of using
this agent as a histamine H2 antagonist in clinical studies for PD.