EXTERNAL AND IMPLANTED PUMPS FOR APOMORPHINE INFUSION IN PARKINSONISM

Continuous delivery of dopaminergic agents to the striatum is a major challenge to improve the treatment of Parkinson's discase. Apomorphine is one of the best candidates because of its solubility and its D1 an d D2 receptor agonist properties. Seventeen Parkinsonian patients suff ering from severe L-dopa-induced on-off effects were treated by contin uous subcutaneous (SC) infusion with a portable minipump. Administrati on of intracerebroventricular (ICV) apomorphine was carried out in 7 m acaca fascicularis monkeys using implanted programmable pumps. Four of the monkeys were made Parkinsonian by MPTP injections. In patients re ceiving apomorphine, the mean duration of daily off periods was reduce d by 61%. Psychiatric side effects were rare but SC nodules occured in all patients and the external infusion method was therefore difficult to implement. In monkeys, the implanted system was well tolerated. IC V apomorphine infusion led to CSF apomorphine concentrations higher th an the same apomorphine dose infused i.m. Motor function was considera bly improved in two MPTP monkeys during the time of ICV infusion and 3 0 min after its arrest. Long-term ICV administration could not be carr ied out because of catheter blockage and/or apomorphine toxicity. SC a nd ICV apomorphine infusions are efficient for controlling motor activ ity in Parkinsonism but long-term toxicity remains to be studied furth er.