A large body of evidence using experimental animal models shows that the nicotinic
cholinergic system is involved in the control of movement under physiological conditions. This work raised the question whether dysregulation of this system may contribute to motor dysfunction and whether drugs targeting
nicotinic acetylcholine receptors (nAChRs) may be of therapeutic benefit in
movement disorders. Accumulating preclinical studies now show that drugs acting at nAChRs improve
drug-induced dyskinesias. The general nAChR agonist
nicotine, as well as several nAChR agonists (
varenicline,
ABT-089 and ABT-894), reduces
l-dopa-induced abnormal
involuntary movements or
dyskinesias up to 60% in parkinsonian nonhuman primates and rodents. These
dyskinesias are potentially debilitating abnormal
involuntary movements that arise as a complication of
l-dopa therapy for
Parkinson's disease. In addition,
nicotine and
varenicline decrease
antipsychotic-induced abnormal
involuntary movements in rodent models of
tardive dyskinesia.
Antipsychotic-induced
dyskinesias frequently arise as a side effect of chronic
drug treatment for
schizophrenia,
psychosis and other
psychiatric disorders. Preclinical and clinical studies also show that the nAChR agonist
varenicline improves balance and coordination in various
ataxias. Lastly,
nicotine has been reported to attenuate the dyskinetic symptoms of
Tourette's disorder. Several nAChR subtypes appear to be involved in these beneficial effects of
nicotine and nAChR drugs including α4β2*, α6β2* and α7 nAChRs (the asterisk indicates the possible presence of other subunits in the receptor). Overall, the above findings, coupled with
nicotine's
neuroprotective effects, suggest that nAChR drugs have potential for future
drug development for
movement disorders.