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

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.

• Authors: J E Ahlskog, M D Muenter, P A Bailey, P M Stevens
• Journal: Archives of neurology (Arch Neurol) Vol. 49 Issue 5 Pg. 560-8 (May 1992) ISSN: 0003-9942 [Print] United States
• PMID: 1580821 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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