Parkinson's disease (PD) is t he second most common form of neurodegenerative disorders
that results from the progressive loss of dopaminergic neurons in the midbrain substantia nigra pars
compacta (SNpc) triggering profound motor perturbation, as well as cognitive, sensory and mood
deficits. Although these symptoms can be improved using currently available dopamine replacement
strategies, they are not able to slow the neurodegenerative process that underlies PD progression. Following
the discovery of the D3 receptor from molecular cloning, it has gained much attention as a potential
therapeutic target for the treatment of PD due to their localization in the limbic regions of the
brain as well as pharmacologic similarity to the D2 receptor subtype. Of particular interest, D3 receptor-
selective agonists appear to have neuroprotective effects apart from their ability to relieve PD symptoms. Owing to the
distinct significance of D3 receptor in mediating diverse neurological effects, it represents a unique target for therapeutic
intervention in PD with much less undesirable side effects. Herein, we review progress in the development of D3 receptorselective
agonist molecules having a broad spectrum of affinities, selectivities as well as unique pharmacological properties
directed at slowing the neurodegeneration process.
Keywords: Dopamine agonist, D3 receptor, Levodopa, Neuroprotection, Parkinson’s disease.
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