Striatal dynorphin system function may be altered in Parkinson's disease. To evaluate whether treatment with a selective dynorphin agonist improves motor symptoms, four parkinsonian patients received single daily injections of spiradoline under controlled conditions. Doses ranging from 1 to 4 micrograms/kg had no discernible effect on motor performance when given alone or in combination with levodopa-carbidopa. Three patients developed dose-limiting adverse effects, especially behavioral alterations. These results suggest that dynorphin replacement strategies, using spiradoline-like kappa-1 agonists, may have limited value in the therapy of patients with Parkinson's disease.

Adult↗

PubMed1991

Somatostatin replacement therapy for Alzheimer dementia.

Somatostatin is consistently diminished in brains of patients with Alzheimer's disease. To evaluate whether pharmacological restoration of this transmitter deficit has therapeutic value, the synthetic analogue octreotide was administered intravenously to 14 Alzheimer patients under double-blind, placebo-controlled conditions. At the highest dose administered, spinal fluid concentrations approximated those found in brains of experimental animals receiving behaviorally effective amounts of the drug. Neuropsychological testing, however, showed no clinically significant improvement. Coadministration of octreotide and physostigmine to 1 patient also failed to improve cognition. Positron emission tomographic studies in 6 patients revealed a generalized decrease in glucose metabolism as a result of octreotide infusion. These findings suggest that stimulation of the somatostatin system has no value in the symptomatic treatment of Alzheimer dementia.

Aged↗