Apomorphine a dopamine receptor agonist was given subcutaneously to 57 levodopa treated parkinsonian patients with refractory off-period disabilities for a median period of 16 months. In 30 given intermittent suprathreshold injections the mean number of hours spent in a disabling off state fell from 6-9 to 2-9. Similar benefit was observed in 21 patients receiving continuous infusions with additional boluses on demand by mini-pump (mean reduction of hours off from 9-9 to 4-5). Twelve patients have been treated for over two years without tachyphylaxis or loss of response. The incidence of neuropsychiatric sideeffects has been low (7%). Six patients failed to show a sustained worthwhile response; severe disabilities during "on"9 periods being the major problem. Subcutaneous apomorphine is proposed as an effective treatment for patients with incapacitating "off" period disabilities refractory to oral medication and should be considered before experimental implantation procedures.The incidence of disabling "on-oft" fluctuations increases with the duration of levodopa treatment and after ten years of sustained therapy most patients are affected.' For the majority treatment is difficult. The use of selegiline,23 partial substitution of levodopa by orally administered dopamine agonists4 and controlled-release levodopa preparations56 may temporarily extend "on" periods in some patients. Subcutaneous apomorphine, a directly acting dopamine agonist with affinity for both D 1 and D2 receptors, rapidly and consistently reverses the "off" period motor deficit.78We have previously described our initial experience with either continuous subcutaneous infusion or intermittent parenteral injection of apomorphine in 19 patients with severe "on-off" fluctuations.9 Eleven patients treated with subcutaneous infusion showed marked and sustained improvement; mean "off' hours per day were reduced from 10-1 to 3-8 and during the remaining "off" periods the mean disability score fell. Comparable results were obtained in eight patients with less severe disabilities given intermittent injections. Other reports have supported these observations. 112 We report our further experience in 57 patients with disabling levodopa related motor oscillations treated with subcutaneous apomorphine for periods up to 32 months.The effects of apomorphine in patients with additional disabilities including biphasic dyskinesias, urinary dysfunction and "oft" period pain, dystonia, dyspnoea, anismus and belching have also been studied. Patients and methodsFifty seven levodopa treated patients with idiopathic Parkinson's disease were treated with apomorphine. In all cases disabling "onoff" fluctuations in motor performance remained despite attempts to improve control by redistribution of levodopa doses, concurrent use of dopamine agonists (57%) or selegiline (91 %), controlled release levodopa preparations (10%), and dietary protein restriction.Their mean age was 58-9 years and disease duration 15 9 years. All patients were admitted to hospital for pre-...

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The magnitude and pattern of motor responses to single doses of subcutaneous apomorphine and oral levodopa were compared in 14 patients with Parkinson's disease. Although apomorphine produced much shorter motor responses than levodopa, the quality of response to the two drugs was virtually indistinguishable. These clinical observations support the notion that integrity of striatal post-synaptic dopamine receptors is a key determinant of responsiveness to dopaminergic treatment in Parkinson's disease.