The symptomatic treatment of Parkinson’s disease (PD) has been dominated by the use of
dopaminergic medication, but significant unmet need remains, much of which is related to
non-motor symptoms and the involvement of non-dopaminergic transmitter systems. As such,
little has changed in the past decades that has led to milestone advances in therapy and
significantly improved treatment paradigms and patient outcomes, particularly in relation to
symptoms unresponsive to levodopa. This review has looked at how pharmacological
approaches to treatment are likely to develop in the near and distant future and will focus on
two areas: 1) novel non-dopaminergic pharmacological strategies to control motor symptoms;
and 2) novel non-dopaminergic approaches for the treatment of non-motor symptoms. The
overall objective of this review is to use a ‘crystal ball’ approach to the future of drug
discovery in PD and move away from the more traditional dopamine-based treatments. Here,
we discuss promising non-dopaminergic and ‘dirty drugs’ that have the potential to become
new key players in the field of Parkinson’s disease treatment.