Technological prospection: patents mapping involving compounds for the treatment of L-DOPA-induced dyskinesias

ABSTRACT

Introduction: Parkinson’s disease (PD), is a disorder debilitant characterized by the reduction of nigrostriatal dopaminergic neurons within the midbrain, specifically in the substantia nigra pars compacta, which results for the dopamine (DA) depletion in the striatum. Dopamine replacement therapies with the 3,4-dihydroxy-L-phenylalanine (Levodopa or L-DOPA) represent the most common strategy to treat PD. However, chronic administration of L-DOPA results in abnormal involuntary movement (AIMs). Thus, the present study aimed to prospect patents of alternative treatment strategies for L-DOPA-induced dyskinesias.

Areas covered: This review covers the therapeutic patents published over the 2001–2019 period in the WIPO, INPI, and ESPACENET, which report treatment strategies for L-DOPA induced dyskinesias (LIDs).

Expert opinion: In recent years, several pharmaceutical companies, as well as universities and researchers have tested effective compounds for LIDs treatment, showing substances that act on central pathways as antagonists and agonists of the serotonergic system, which may result in the key to onset of LIDs in animal models of PD. Future works aiming to elucidate the L-DOPA, Flibanserin, Eltoprazine, and Pridopidina mechanisms of action on the receptors of the serotonergic system and D₂ receptors of the indirect pathway, will allow the development of effective therapies for LIDs.

KEYWORDS:

• Patents
• dyskinesias
• technological prospection
• abnormal involuntary movement

Article highlights

• Parkinson’s disease (PD) therapy is centered to replace the loss of striatal dopamine

• L-DOPA-induced dyskinesias are common and serious complications of long‐term treatment with L-dopa

• L-DOPA-induced dyskinesias are common and serious complications of long‐term treatment with L-dopa

• The etiopathogenesis mechanisms underlying of the LID and involuntary movements are still largely unclear, though pulsatile stimulation of post-synaptic striatal receptors appears to be important in their genesis

• The pharmacological effect of these compounds was evaluated in pre-clinical studies and the exact mechanism of action and safety should be further evaluated

• There is hope that new drugs for the L-dopa-induce dyskinesia are presented and launched in the market in the next years

Author contributions

The authors S da Silva Barroso and LE Sena Lopes contributed to conceptualization; investigation and validation phases; S da Silva Barroso, K Silva Santos, and M Zanardo Gomes designed the study, supervised the work, analysis of the data, drafted the paper and contributed to critical reading of the manuscript.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Supplementary material

Supplemental data for this article can be accessed here.

Additional information

Funding

This paper was not funded.