MECHANISMS AND ISSUES RELATING TO THE USE OF Dl-LIKE DOPAMINE RECEPTOR AGONISTS FOR AGE-RELATED ILLNESSES: PARKINSON'S DISEASE AND MEMORY AND COGNITION

摘要

Parkinson's disease is the second most common age related neurodegenerative disorder that, along with age-related declines in memory and cognition, represents an area of medicine in which there have not been major advances in decades. This paper will focus on the great potential that D_1-like dopamine agonists may have in these arenas. Although levodopa has been the most effective treatment for Parkinson's disease (PD), pharmacokinetic and bioconversion problems have led to efforts to develop direct acting "dopamine agonists for PD. Although the large majority of research and development has been focused on D2-like direct agonists, this talk will show data illustrating why D_1 agonists should be a high priority pharmacotherapeutic target for treatment of PD. This presentation will review the neurobiological and molecular pharmacological evidence that supports this hypothesis, some of the scientific hurdles, and the current state of the medicinal chemistry of D_1 agonist development. The concluding portion of the talk will review the experimental evidence suggesting that Di-like agonists can lead to improvements in memory and cognitive function, and review the current status of drug discovery and development for these uses.