Dopamine agonist treatment of fluctuating parkinsonism. D-2 (controlled-release MK-458) vs combined D-1 and D-2 (pergolide)
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.
Ahlskog
J E
JE
Department of Neurology, Mayo Clinic, Rochester, MN 55905.
Muenter
M D
MD
Bailey
P A
PA
Stevens
P M
PM
D000328:Adult; D000368:Aged; D000978:Antiparkinson Agents / Q000627:therapeutic use; D002230:Carbidopa / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005260:Female; D006801:Humans; D007785:Lactose / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D007980:Levodopa / Q000627:therapeutic use; D008297:Male; D008747:Methylcellulose / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008875:Middle Aged; D010078:Oxazines; D010300:Parkinson Disease / Q000188:drug therapy*; D010479:Pergolide / Q000008:administration & dosage / Q000627:therapeutic use*
D000978:Antiparkinson Agents; D004338:Drug Combinations; D010078:Oxazines; C009265:carbidopa, levodopa drug combination; D010479:Pergolide; D007980:Levodopa; D008747:Methylcellulose; C071191:MK 458; D007785:Lactose; D002230:Carbidopa