Suitability of the adenosine antagonist istradefylline for the treatment of Parkinson's disease: pharmacokinetic and clinical considerations.

Abstract

INTRODUCTION:

Recent experimental and clinical research has shown that A2A adenosine receptor antagonism can bring about an improvement in the motor behavior of patients with Parkinson's disease. Istradefylline , a xanthine derivative, has the longest half-life of all the currently available A2A adenosine receptor antagonists; it can successfully permeate through the blood-brain barrier and has a high human A2A adenosine receptor affinity.

AREAS COVERED:

In this article, the author discusses the potential role of A2A adenosine receptor antagonists in the treatment of Parkinson's disease through the evaluation of istradefylline. Specifically, the article reviews the clinical and pharmacokinetic information available to elucidate its therapeutic potential.

EXPERT OPINION:

A2A adenosine receptor antagonists are efficacious in combination with l-dopa. l-dopa has a complex pharmacokinetic behavior and causes long-term behavioral and metabolic side effects. Future research on A2A adenosine receptor antagonism should consider compounds like istradefylline as l-dopa and/or dopamine agonist-sparing treatment alternatives, since their clinical handling, safety and side-effect profile are superior to l-dopa and/or dopamine agonists. The current focus to demonstrate a specific dyskinesia-ameliorating efficacy of A2A adenosine receptor antagonism in clinical trials is risky, since the presentation of dyskinesia varies on a day-to-day basis and is considerably influenced by peripheral l-dopa metabolism. The demonstration of an antidyskinetic effect may convince authorities, but this is far less relevant in clinical practice as patients generally better tolerate dyskinesia than other phenomena and dopaminergic side effects.

• Authors: Thomas Müller
• Journal: Expert opinion on drug metabolism & toxicology (Expert Opin Drug Metab Toxicol) Vol. 9 Issue 8 Pg. 1015-24 (Aug 2013) ISSN: 1744-7607 [Electronic] England
• PMID: 23642267 (Publication Type: Journal Article, Review)

Chemical References

• Adenosine A2 Receptor Antagonists
• Dopamine Agonists
• Purines
• istradefylline
• Levodopa
• Adenosine

Topics

• Adenosine (antagonists & inhibitors, metabolism)
• Adenosine A2 Receptor Antagonists (administration & dosage, adverse effects, pharmacokinetics)
• Animals
• Blood-Brain Barrier (metabolism)
• Disease Models, Animal
• Dopamine Agonists (pharmacology)
• Dyskinesias (drug therapy)
• Half-Life
• Humans
• Levodopa (administration & dosage, adverse effects, pharmacokinetics)
• Parkinson Disease (drug therapy)
• Purines (administration & dosage, adverse effects, pharmacokinetics)
• Treatment Outcome