Parkinson's disease monotherapy with controlled-release MK-458 (PHNO): double-blind study and comparison to carbidopa/levodopa.
The potent and selective dopamine D-2 agonist, MK-458 [PHNO; (+)-4-propyl-9-hydroxynaphthoxazine] was administered as monotherapy to nine patients with Parkinson's disease in a double-blind, placebo-controlled 12-week investigation; ten other patients were randomized to placebo. MK-458 was formulated as a controlled-release preparation, using a hydroxypropyl methylcellulose-lactase (HPMC) matrix. Patients receiving MK-458/HPMC improved on a variety of measures of parkinsonism, compared to their baseline scores; in contrast, only trivial improvement was seen within the placebo group. We subsequently compared the anti-Parkinson response to MK-458/HPMC with the response to chronic carbidopa/levodopa monotherapy in an open label trial. Carbidopa/levodopa improved parkinsonism to a significantly greater degree than MK-458/HPMC. Doses of MK-458 used in these studies (up to 60 mg per day) were substantially higher than those in previously reported preliminary studies of this medication. We conclude that monotherapy with MK-458/HPMC results in a significant anti-Parkinson effect; however, the response falls short of that seen with carbidopa/levodopa.
Department of Neurology, Mayo Clinic, Rochester, Minnesota 55905.
J E
JE
Ahlskog
M D
MD
Muenter
P A
PA
Bailey
P M
PM
Miller
D000328:Adult; D000368:Aged; D002230:Carbidopa / Q000627:therapeutic use*; D003692:Delayed-Action Preparations; D015259:Dopamine Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010078:Oxazines / Q000008:administration & dosage / Q000627:therapeutic use*; D010300:Parkinson Disease / Q000188:drug therapy* / Q000523:psychology
D003692:Delayed-Action Preparations; D015259:Dopamine Agents; D010078:Oxazines; C042631:naxagolide; D007980:Levodopa; D002230:Carbidopa