The treatment of
dyskinesia in Parkinson׳s disease remains poor but
H3 receptor agonists have been suggested as a novel pharmacological approach. We examined the effects of the
H3 agonist,
immepip, in 6-OHDA-lesioned rats exhibiting AIMs (abnormal
involuntary movements), a rat analogue of
dyskinesia, in response to
l-dopa compared to the known anti-dyskinetic agents
amantadine,
MK-801 and 8-OHDPAT. We then attempted to extend these studies in to dyskinetic
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (
MPTP) treated common marmosets.
Amantadine,
MK-801 and 8-OHDPAT all dose-dependently reduced
l-dopa-induced axial, lingual and oral (ALO) AIMs in 6-OHDA-lesioned animals accompanied by a reduction in contralateral rotation with higher doses of
amantadine and
MK-801. By contrast,
immepip had no effect on AIMs expression or contralateral rotation. In the
MPTP-treated common marmoset exhibiting
dyskinesia to
l-dopa,
immepip alone induced retching and in combination with
l-dopa administered subcutaneously or orally induced the rapid onset of retching and
vomiting which was not controlled by pretreatment with
domperidone. Administration of the unrelated
H3 agonist,
imetit had the same effect. Despite causing negative side-effects, it appears that both agonists reduced the antiparkinsonian response to
l-dopa resulting in reduced
dyskinesia.
H3 agonists appear unlikely candidates for the treatment of
dyskinesia in PD based on lack of evidence of efficacy and potential adverse effects.