Abstract

This article reviews the role of the D1-like dopamine receptors in Parkinson's disease (PD), an idea supported by the location of D1 receptors in key aspects of basal ganglia circuitry. The initial disappointing results with available partial D1 agonists have been replaced by optimism as newer full D1 agonists have been shown to be the only class of drugs that can decrease parkinsonism in primates to a degree comparable to levodopa. Most of the available D1 agonists, however, have been plagued by several problems, including poor bioavailability due, at least in part, to the necessity of a catechol function. Three other development issues that have hampered some members of this class are tolerance, hypotension and seizures, although some of the newer drugs entering early development may have escaped these problems. Finally, scientific advances have suggested that therapeutic profiles may be improved either by targeting only one of the two D1-like receptors or by developing drugs that can activate selectively only some D1-mediated functions. These examples suggest that it is highly likely that the immense therapeutic potential of D1 agonists will be realized in PD and several other important CNS disorders before the end of the decade.

Original languageEnglish (US)
Pages (from-to)1582-1591
Number of pages10
JournalCurrent Opinion in Investigational Drugs
Volume2
Issue number11
StatePublished - Dec 4 2001

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Dopamine D1 Receptors
Parkinson Disease
Pharmaceutical Preparations
Parkinsonian Disorders
Levodopa
Basal Ganglia
Hypotension
Primates
Biological Availability
Seizures
Therapeutics

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Drug Discovery

Cite this

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title = "Parkinson's disease and D1 dopamine receptors",
abstract = "This article reviews the role of the D1-like dopamine receptors in Parkinson's disease (PD), an idea supported by the location of D1 receptors in key aspects of basal ganglia circuitry. The initial disappointing results with available partial D1 agonists have been replaced by optimism as newer full D1 agonists have been shown to be the only class of drugs that can decrease parkinsonism in primates to a degree comparable to levodopa. Most of the available D1 agonists, however, have been plagued by several problems, including poor bioavailability due, at least in part, to the necessity of a catechol function. Three other development issues that have hampered some members of this class are tolerance, hypotension and seizures, although some of the newer drugs entering early development may have escaped these problems. Finally, scientific advances have suggested that therapeutic profiles may be improved either by targeting only one of the two D1-like receptors or by developing drugs that can activate selectively only some D1-mediated functions. These examples suggest that it is highly likely that the immense therapeutic potential of D1 agonists will be realized in PD and several other important CNS disorders before the end of the decade.",
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Parkinson's disease and D1 dopamine receptors. / Mailman, Richard; Huang, Xuemei; Nichols, D. E.

In: Current Opinion in Investigational Drugs, Vol. 2, No. 11, 04.12.2001, p. 1582-1591.

Research output: Contribution to journalReview article

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AU - Nichols, D. E.

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