The potential of activation of somatostatinergic neurotransmission with FK960 in Alzheimer's disease.
Somatostatin levels are reduced in post mortem brains of patients with Alzheimer's disease (AD). FK960 is a somatostatin-releasing agent. After oral administration to rhesus monkeys, FK960 is distributed to the entire brain. In patients with AD, regional cerebral blood flow and regional cerebral metabolic rate of glucose correlate with cognitive decline and the appearance of pathological changes. Aged rhesus monkeys are a good animal model of AD as they develop age-associated cognitive impairment. FK960 (1 mg/kg) caused modest increases in regional cerebral blood flow and regional cerebral metabolic rate of glucose in aged monkeys, suggesting that FK960 will improve cognition. Thus, the activation of somatostatinergic neurotransmission, with FK960 or a similar drug, has considerable potential in the treatment of cognitive impairment.
Doggrell
Sheila A
SA
Doggrell Biomedical Communications, 47 Caronia Crescent, Lynfield, Auckland, New Zealand. s_doggrell@yahoo.com
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D001549:Benzamides / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000098:blood supply / Q000378:metabolism; D002560:Cerebrovascular Circulation / Q000187:drug effects; D004195:Disease Models, Animal; D005947:Glucose / Q000378:metabolism; D006801:Humans; D008253:Macaca mulatta; D018377:Neurotransmitter Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D010879:Piperazines / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013004:Somatostatin / Q000378:metabolism
D001549:Benzamides; C102991:N-(4-acetyl-1-piperazinyl) -4-fluorobenzamide monohydrate; D018377:Neurotransmitter Agents; D010879:Piperazines; D013004:Somatostatin; D005947:Glucose