Continuous dopaminergic stimulation reduces risk of motor complications in parkinsonian primates.
Levodopa or short-acting dopamine (DA) agonist treatment of advanced parkinsonian patients exposes striatal DA receptors to non-physiologic intermittent stimulation that contributes to the development of dyskinesias and other motor complications. To determine whether continuous dopaminergic stimulation can delay or prevent onset of motor complications, four MPTP-lesioned, levodopa-naive cynomolgus monkeys were implanted subcutaneously with apomorphine containing ethylene vinyl acetate rods. Three other MPTP-lesioned monkeys received daily injections of apomorphine. Animals receiving apomorphine rods showed improved motor function ('ON' state) within 1 day of implantation, and remained continually 'ON' for the duration of treatment (up to 6 months) without developing dyskinesias. Injected animals also showed similar improvement in motor function after each apomorphine injection. However, these primates remained 'ON' for only 90 min and within 7-10 days all developed severe dyskinesias. Implanted monkeys evidenced local irritation, which was alleviated by steroid co-therapy.
Bibbiani
Francesco
F
Experimental Therapeutic Branch, Building 10, Room 5C103, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD 20892-1406, USA.
Costantini
Lauren C
LC
Patel
Raj
R
Chase
Thomas N
TN
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D000978:Antiparkinson Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001058:Apomorphine / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D004195:Disease Models, Animal; D018491:Dopamine Agonists / Q000008:administration & dosage* / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004343:Drug Implants; D020820:Dyskinesias / Q000209:etiology / Q000517:prevention & control*; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy; D007279:Injections, Subcutaneous; D008252:Macaca fascicularis; D008297:Male; D009068:Movement / Q000187:drug effects; D020734:Parkinsonian Disorders / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D011145:Polyvinyls / Q000008:administration & dosage / Q000009:adverse effects; D020127:Recovery of Function / Q000187:drug effects; D013256:Steroids / Q000627:therapeutic use
D000978:Antiparkinson Agents; D018491:Dopamine Agonists; D004343:Drug Implants; D011145:Polyvinyls; D013256:Steroids; C016438:ethylenevinylacetate copolymer; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D001058:Apomorphine