The short‐duration response to apomorphine: Implications for the mechanism of dopaminergic effects in parkinsonism

Stephen T. Gancher, William R. Woodward, Perry Gliessman, Brian Boucher, John G. Nutt

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

The pharmacological basis of the short‐duration response to dopaminergic stimulation in parkinsonism is not completely understood. Whereas it is generally assumed that the response reflects concurrent dopamine receptor occupancy, it is also possible that receptor activation triggers events that outlast the time that receptors are occupied by agonist. To distinguish between these two possibilities, we administered apomorphine, a mixed D1‐D2 agonist with rapid equilibration between plasma and brain, to patients with parkinsonism. The clinical response to apomorphine injections lagged behind peak plasma concentrations and persisted beyond the time plasma apomorphine concentrations fell below threshold levels, which were estimated from peak plasma apomorphine concentrations following ineffective doses. We conclude that dopaminergic stimulation triggers effects that outlast the period of receptor occupancy by agonist. Understanding these steps may offer new pharmacological therapies for parkinsonism.

Original languageEnglish (US)
Pages (from-to)660-665
Number of pages6
JournalAnnals of Neurology
Volume27
Issue number6
DOIs
StatePublished - Jun 1990

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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