Pardoprunox Hydrochloride

This review summarizes currently available treatment options and treatment strategies, investigational treatments, and the importance of exercise for early Parkinson's disease.

The available treatment options for early Parkinson's disease have changed little in the past decade and include carbidopa/levodopa, dopamine agonists, and monoamine oxidase type B (MAO-B) inhibitors. However, we discuss changes in treatment strategies, including dosing and the use of combination therapy used in an attempt to reduce or delay the appearance of motor complications and other adverse events. We will also review several investigational treatments that have shown promise for the treatment of early Parkinson's disease, including a new extended release formulation of carbidopa/levodopa (IPX066), safinamide which inhibits MAO-B, dopamine uptake and glutamate and pardoprunox which is a 5HT-1A agonist and a partial dopamine agonist. Finally, we discuss recent studies focusing on exercise as an important component in the management of early Parkinson's disease.

Advances in the management of early Parkinson's disease include evolving treatment strategies, new investigational treatments, and earlier implementation of various forms of exercise.

Psychiatric disorders like schizophrenia and neurodegenerative diseases like Parkinson's disease are associated with poly-factorial pathogenic mechanisms, with several neurotransmitter systems closely involved. In addition to the cerebral dopaminergic (DA) system, the serotoninergic (5-HT) system also plays a crucial role in regulating psychoemotional, cognitive and motor functions in the central nervous system (CNS). Among the large 5-HT receptor family, accumulating data have revealed new insights into the therapeutic benefit of the 5-HT1A receptor in treating various CNS disorders, especially schizophrenia and Parkinson's disease. The present review discusses the advance of dual agents with mixed actions at the dopamine D2 and serotonin 5-HT1A receptors in the treatment of these diseases. Aripiprazole was the only marketed drug with dual D2 and 5-HT1A profile. It is a partial D2 and 5-HT1A receptor agonist and has been prescribed as an atypical antipsychotical drug. Two other drugs Cariprazine and Pardoprunox are being investigated in clinic. Most of the other candidate compounds, including Bifeprunox, Sarizotan, Mazapertine succinate, PF-217830, and Adoprazine were discontinued due to either non-optimal pharmacokinetic properties or insufficient therapeutical efficacy. Although much effort has been done to highlight the advantages of the 5-HT1A and D2 dual approach, it has to be pointed out that many of these drugs showed poly-pharmacological profile by targeting many other receptors and/or transporters besides the D2 and 5-HT1A receptors. In this regard, 'pure' compounds exclusively acting on the D2 and 5-HT1A receptors are highly needed to further validate this approach. Meanwhile, safety concerns and in vivo pharmacokinetic alerts should also be implanted to the drug design art early.