Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

N-(4-Acetyl-1-piperazinyl)-4-fluorobenzenesulfonamide (FR121196), a newly introduced putative cognitive enhancer of a derivative of piperazine, was investigated for its effects on long-term potentiation in guinea-pig hippocampal slices. The magnitude of long-term potentiation of population spikes recorded in CA3 pyramidal neurons was significantly augmented by perfusing FR121196 (10(-9)-10(-6) M) for 25 min before and during tetanic stimulation of the mossy fibers; the basal amplitude of population spikes before tetanus was hardly affected by the drug. The dose-response curve was bell-shaped with a maximal augmentation at 10(-7) M. Similar activity and bell-shaped dose-response curve were observed with methamphetamine (10(-8)-10(-6) M). Physostigmine (10(-8)-10(-6) M) also facilitated long-term potentiation of this pathway and the magnitude of augmentation was concentration-dependent. Scopolamine (10(-6) M) per se had little effect on the magnitude of long-term potentiation in the mossy fiber-CA3 pathway, but significantly attenuated its enhancement by FR121196 (10(-7) M) and physostigmine (10(-6) M), although it failed to influence that by methamphetamine (10(-7) M). In hippocampal slices from animals treated with cysteamine, which was shown to deplete hippocampal somatostatin, FR121196 (10(-7) M) hardly affected long-term potentiation generation, whereas physostigmine (10(-6) M) and methamphetamine (10(-7) M) augmented it significantly. These results suggest that FR121196 enhances the development of long-term potentiation in the mossy fiber-CA3 pathway through activation of somatostatinergic neurons in the hippocampal formation.
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PMID:Role of somatostatin in the augmentation of hippocampal long-term potentiation by FR121196, a putative cognitive enhancer. 790 Oct 36

A 58-year-old man developed progressive difficulty with comprehension and verbal output with dementia. Positron emission tomography with 18F 2-fluoro-2-deoxy-D-glucose demonstrated asymmetrical frontal and anterior temporal lobe loss of glucose use. Scopolamine infusion (0.3 mg) did not influence memory. Postmortem studies revealed evidence of Pick's disease, with Pick bodies, loss of somatostatin, preservation of choline acetyltransferase and immunostaining with neurofilament antibodies. Pharmacological challenge and positron imaging offer valuable means for the noninvasive assessment of dementing illness. The contributions of functional imaging to our knowledge of frontal involvement in dementing illness are reviewed.
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PMID:Functional imaging, the frontal lobes, and dementia. 840 92

With passive avoidance (PA), Morris water maze (WM) and eight-arm radial maze tasks, we evaluated the memory-enhancing action of FK960 [N-(4-acetyl-1-piperazinyl)-p-fluorobenzamide monohydrate], a compound which we have found through rational drug screening based on our hypothesis that penile erection is a valid predictor of central cholinergic activation. Memory performance in the tasks was impaired in aged (24- to 26-months-old) rats as well as in rats with nucleus basalis magnocellularis lesions. Scopolamine (1 mg/kg i.p.) treatment induced memory impairment in PA and WM; treatment with cysteamine (200 mg/kg s.c.) induced memory impairment in PA but not in WM, whereas fimbria fornix lesioning affected the rats in the opposite manner. FK960 (0.1-10 mg/kg i.p.) ameliorated all the memory impairments except those induced by cysteamine or fimbria fornix lesion, and the dose-response curves were bell shaped with maximal response at 1 to 3.2 mg/kg. The effects of FK960 on the scopolamine-induced memory impairment in the PA and/or WM were abolished by cysteamine (200 mg/kg s.c.), dl-p-chlorophenylalanine methyl ester hydrochloride (150 mg/kg i.p. for 3 days) or raphe lesioning, but not by neonatal 6-hydroxydopamine (35 micrograms/head) treatment. Neurochemical analysis revealed that cysteamine and raphe lesions reduced brain somatostatin and serotonin contents, respectively. The treatment with FK960 (0.32-320 mg/kg p.o.) dose-dependently increased both serotonin and 5-hydroxyindoleacetic acid levels in the brain areas examined and significantly increased hippocampal somatostatin contents at the smaller doses. From these results, we conclude that FK960 ameliorates cognitive dysfunction through an activation of the somatostatinergic-serotonergic link.
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PMID:FK960 N-(4-acetyl-1-piperazinyl)-p-fluorobenzamide monohydrate ameliorates the memory deficits in rats through a novel mechanism of action. 896 37

Our previous studies have demonstrated that FK960 (FR59960; N-(4-acetyl-1-piperazinyl)-p-fluorobenzamide monohydrate), a novel antidementia piperazine derivative, exerts beneficial effects on memory deficits in various animal models of amnesia in rats [M. Yamazaki, N. Matsuoka, N. Maeda, Y. Ohkubo, I. Yamaguchi, FK960 N-(4-acetyl-1-piperazinyl)-p-fluorobenzamide monohydrate ameliorates the memory deficits in rats through a novel mechanism of action, J. Pharmacol. Exp. Ther., 279 (1996) 1157-1173.] and in rhesus monkeys [N. Matsuoka, T.G. Aigner, FK960 [N-(4-acetyl-1-piperazinyl)-p-fluorobenzamide monohydrate], a novel potential antidementia drug, improves visual recognition memory in rhesus monkeys: comparison with physostigmine, J. Pharmacol. Exp. Ther., 280 (1997) 1201-1209]. To clarify the synaptic mechanisms of its antiamnesic action, FK960 was investigated for its effects on the development of long-term potentiation (LTP) in guinea-pig hippocampal slices. The magnitude of LTP of population spike recorded in CA3 pyramidal neurons was significantly augmented by perfusing FK960 (10-9-10-6 M) for 25 min before and during tetanic stimulation of the mossy fibers, whereas the basal amplitude of population spikes before tetanus was hardly affected by the drug. The dose-response curve was bell-shaped with a maximal augmentation at 10-7 M. Scopolamine (10-6 M) per se had little effect on the magnitude of LTP in the mossy fiber-CA3 pathway, but significantly attenuated its enhancement by FK960 (10-7 M). In hippocampal slices from animals treated with cysteamine (200 mg/kg, s.c.), which was shown to deplete the hippocampal somatostatin, FK960 (10-7 M) hardly affected the LTP. These results suggest that FK960 enhances the magnitude of LTP in the mossy fiber-CA3 pathway through an activation of the cholinergic-somatostatinergic link in the hippocampal formation. Furthermore, it can be postulated that the drug regulates the cognitive function by modulating directly synaptic plasticity in the hippocampal neuronal network.
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PMID:FK960, a novel potential anti-dementia drug, augments long-term potentiation in mossy fiber-CA3 pathway of guinea-pig hippocampal slices. 962 44