Distribution of a somatostatin analog after continuous intraventricular administration

Abstract

Decreased somatostatin in the brains of patients with Alzheimer's disease has led to an investigation of the efficacy of neurotransmitter replacement therapy. The distribution of a somatostatin analog, octreotide, was determined after 2 to 6 days of continuous intraventricular infusion at 40 micrograms/h in dogs. The tissue concentration was greater than 100 ng/g wet weight in all parts of the brain, which is greater than the normal concentration of native somatostatin. There was no reduction in native somatostatin production because of the infusion of the analog. The cerebrospinal fluid octreotide concentration was 1000 times greater than the plasma concentration. The results demonstrate that neurotransmitter replacement for somatostatin can be achieved by chronic intraventricular infusion of a metabolically stable analog.