Irregularities in motor response after continuing levodopa therapy of Parkinson disease (the "on-off effect") were assessed with the addition of l-α-methydopa hydrazine (carbidopa) in a doubleblind study. Thirteen of 20 patients improved while receiving carbidopa and levodopa while only four of 17 patients improved while receiving placebo and levodopa. Twenty-three of 37 patients improved in a subsequent non-blind trial of carbidopa plus levodopa.
Improvement was not dependent on an increase in dose or frequency of levodopa administration. Adverse effects included dyskinesia, imbalance, and confusion; nausea was eliminated. One patient died of glomerulonephritis that predated the drug trial, but worsened progressively during and after it. Carbidopa's suppression of the "on-off effect" suggests that extracerebral factors may be important in this phenomenon.
Sweet RD, McDowell FH, Wasterlain CG, Stern PH. Treatment of "On-Off Effect" With A Dopa Decarboxylase Inhibitor. Arch Neurol. 1975;32(8):560–563. doi:10.1001/archneur.1975.00490500080010