Time interval between repeated injections conditions the duration of motor improvement to apomorphine in Parkinson's disease

Behavioral hyposensitivity to repeated apomorphine administration occurs in fluctuating parkinsonian patients. To determine to what extent the interval between doses influences the response, we administered equal paired apomorphine injections to 10 fluctuating parkinsonian patients. Subjects received two apomorphine injections at 2-hour and at 4-hour intervals on different days after a 10- to 12-hour overnight period without levodopa. Following apomorphine doses at 2-hour intervals, the duration of response was reduced by 40 (61 versus 42 minutes, p< 0.001) but was of equal duration when the doses were given at 4-hour intervals. These findings indicate that the interval between doses is a critical determinant of motor response. We postulate a time-dependent period of partial hyposensitivity to pulsatile DA stimulation.