Dopamine agonist treatment of fluctuating parkinsonism. D-2 (controlled-release MK-458) vs combined D-1 and D-2 (pergolide)

Arch Neurol. 1992 May;49(5):560-8. doi: 10.1001/archneur.1992.00530290152026.

Abstract

Adjunctive treatment with the very potent and selective dopamine D-2 agonist MK-458 (controlled-release formulation) improved the control of parkinsonism in patients with fluctuating responses to levodopa therapy (with carbidopa). We subsequently switched patients to adjunctive treatment with pergolide, a less potent D-2 agonist. Pergolide therapy controlled parkinsonism more effectively than controlled-release MK-458. Unlike MK-458, pergolide mesylate also has D-1 agonist properties, apparently accounting for its greater antiparkinsonism efficacy. Adjunctive treatment with controlled-release MK-458 elicited less choreiform dyskinesias than either pergolide adjunctive therapy or therapy with carbidopa-levodopa alone; this finding suggests that D-1 receptor stimulation contributes to the elicitation of medication-induced chorea. The highest doses of controlled-release MK-458 resulted in paradoxical freezing of gait in almost one third of patients. This finding suggests that gait freezing, common in untreated parkinsonism, can also be elicited by excessive D-2 stimulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antiparkinson Agents / therapeutic use
  • Carbidopa / therapeutic use
  • Dose-Response Relationship, Drug
  • Drug Combinations
  • Female
  • Humans
  • Lactose / administration & dosage
  • Lactose / adverse effects
  • Lactose / analogs & derivatives*
  • Lactose / therapeutic use
  • Levodopa / therapeutic use
  • Male
  • Methylcellulose / administration & dosage
  • Methylcellulose / adverse effects
  • Methylcellulose / analogs & derivatives*
  • Methylcellulose / therapeutic use
  • Middle Aged
  • Oxazines
  • Parkinson Disease / drug therapy*
  • Pergolide / administration & dosage
  • Pergolide / therapeutic use*

Substances

  • Antiparkinson Agents
  • Drug Combinations
  • Oxazines
  • carbidopa, levodopa drug combination
  • Pergolide
  • Levodopa
  • Methylcellulose
  • MK 458
  • Lactose
  • Carbidopa