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 disease. Apomorphine is one of the best candidates because of its solubility and its D1 and D2 receptor agonist properties. Seventeen Parkinsonian patients suffering from severe L-dopa-induced on-off effects were treated by continuous subcutaneous (SC) infusion with a portable minipump. Administration of intracerebroventricular (ICV) apomorphine was carried out in 7 macaca fascicularis monkeys using implanted programmable pumps. Four of the monkeys were made Parkinsonian by MPTP injections. In patients receiving apomorphine, the mean duration of daily off periods was reduced by 61%. Psychiatric side effects were rare but SC nodules occurred in all patients and the external infusion method was therefore difficult to implement. In monkeys, the implanted system was well tolerated. ICV apomorphine infusion led to CSF apomorphine concentrations higher than the same apomorphine dose infused i.m. Motor function was considerably improved in two MPTP monkeys during the time of ICV infusion and 30 min after its arrest. Long-term ICV administration could not be carried out because of catheter blockage and/or apomorphine toxicity. SC and ICV apomorphine infusions are efficient for controlling motor activity in Parkinsonism but long-term toxicity remains to be studied further.
Pollak
P
P
Department of Clinical and Biological Neurosciences, INSERM U-318, Joseph Fourier University of Grenoble, France.
Benabid
A L
AL
Limousin
P
P
Gervason
C L
CL
Jeanneau-Nicolle
E
E
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000818:Animals; D001058:Apomorphine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D015918:Infusion Pumps, Implantable; D008252:Macaca fascicularis; D008297:Male; D008875:Middle Aged; D009043:Motor Activity / Q000187:drug effects; D010300:Parkinson Disease / Q000188:drug therapy*; D011954:Receptors, Dopamine / Q000187:drug effects
D011954:Receptors, Dopamine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D001058:Apomorphine