piperidines and ethylcholine-aziridinium

Topics: Animals; Aziridines; Choline; Colchicine; Folic Acid; Glutamates; Glutamic Acid; Ibotenic Acid; Kainic Acid; Lectins; Mitogens; Mustard Compounds; Nerve Degeneration; Nervous System; Neurons; Piperidines; Pyrrolidonecarboxylic Acid; Quinolinic Acid; Quinolinic Acids

Recently, numerous medicinal plants possessing profound central nervous system effects and antioxidant activity have received much attention as food supplement to improve cognitive function against cognitive deficit condition including in Alzheimer's disease condition. Based on this information, the effect of piperine, a main active alkaloid in fruit of Piper nigrum, on memory performance and neurodegeneration in animal model of Alzheimer's disease have been investigated. Adult male Wistar rats (180-220 g) were orally given piperine at various doses ranging from 5, 10 and 20mg/kg BW at a period of 2 weeks before and 1 week after the intracerebroventricular administration of ethylcholine aziridinium ion (AF64A) bilaterally. The results showed that piperine at all dosage range used in this study significantly improved memory impairment and neurodegeneration in hippocampus. The possible underlying mechanisms might be partly associated with the decrease lipid peroxidation and acetylcholinesterase enzyme. Moreover, piperine also demonstrated the neurotrophic effect in hippocampus. However, further researches about the precise underlying mechanism are still required.

Topics: Acetylcholinesterase; Alkaloids; Alzheimer Disease; Animals; Aziridines; Benzodioxoles; Choline; Cognition Disorders; Donepezil; Hippocampus; Indans; Injections, Intraventricular; Lipid Peroxidation; Male; Malondialdehyde; Maze Learning; Nerve Degeneration; Neuromuscular Blocking Agents; Neuroprotective Agents; Nootropic Agents; Piper nigrum; Piperidines; Polyunsaturated Alkamides; Rats; Space Perception; Thailand

Selegiline, a monoamine oxidase-B inhibitor, is reported to improve memory and learning in dementia of Alzheimer's type. However, only a few studies have reported its use in animal models. Here, we evaluated the effects of selegiline only or its combined use with donepezil, a selective acetylcholinesterase inhibitor on memory impairment, using a Morris water maze. Selegiline dose-dependently attenuated ethylcholine aziridinium ion-induced memory impairment. Co-administration of selegiline and donepezil, at doses that do not exert efficacy individually, significantly ameliorated scopolamine+p-chlorophenylalanine-induced memory deficits. These results suggest that selegiline improves memory impairment mediated by the cholinergic system, and provide evidence of the usefulness of co-treatment with selegiline and donepezil for treating spatial deficits in dementia.

Topics: Analysis of Variance; Animals; Antiparkinson Agents; Aziridines; Behavior, Animal; Choline; Cholinesterase Inhibitors; Donepezil; Dose-Response Relationship, Drug; Drug Synergism; Escape Reaction; Fenclonine; Indans; Male; Maze Learning; Memory Disorders; Piperidines; Rats; Rats, Inbred F344; Reaction Time; Scopolamine; Selegiline; Time Factors

Comparative effects of cholinesterase inhibitors (ChEI) huperzine A with E2020 and tacrine on the radial maze performance in ethylcholine mustard aziridinium ion (AF64A)-treated rat and inhibition of cholinesterase activity were studied. The intracerebroventricular (i.c.v.) injection of AF64A (3 nmol/side) caused significant impairment in the rat's ability to fulfill the partially baited maze paradigm. Oral huperzine A (0.5-0.8 mg/kg), E2020 (1.0-2.0 mg/kg), and tacrine (8.0 mg/kg) effectively reversed AF64A-induced working memory deficit. The doses that improved AF64A-induced memory deficit were correlated to about 25-30% (huperzine A) and less than 10% (E2020, tacrine) inhibition of acetylcholinesterase (AChE) activity in the cortex and hippocampus. Huperzine A, E2020 and tacrine all produced dose-dependent inhibition of brain AChE following i.c.v. and oral administration. Oral huperzine A exhibited higher efficacy on the inhibition of AChE in the cortex and hippocampus than those of E2020 and tacrine. Tacrine was more effective in inhibiting plasma butyrylcholinesterase (BuChE) than it was brain AChE. Conversely, the BuChE activity was less affected by huperzine A and E2020. The results showed that huperzine A had high bioavailability and more selective inhibition on AChE activity in cortex and hippocampus. Huperzine A fits more closely with the established criteria for an ideal AChE inhibitor to be used in clinical studies.

Topics: Alkaloids; Animals; Aziridines; Choline; Choline O-Acetyltransferase; Cholinesterase Inhibitors; Cholinesterases; Donepezil; Dose-Response Relationship, Drug; Female; Indans; Injections, Intraventricular; Male; Maze Learning; Memory; Memory, Short-Term; Neuromuscular Blocking Agents; Piperidines; Rats; Rats, Sprague-Dawley; Sesquiterpenes; Tacrine

Normal aged rats (26 months) displayed significant impairments in learning the Morris water maze task as compared with young adult rats (3 months). The learning deficits of aged basal forebrain (BF)-lesioned rats (26 months; ethylcholine aziridinium ion was injected into the bilateral basal forebrain at 3 months age) were more severe than those of normal aged rats. Choline acetyltransferase (ChAT) in the frontal cortex of aged BF-lesioned rats activity was significantly reduced, but not in normal aged rats which level was almost the same as that in young adult rats. Histological examination showed that cholinergic fibers (acetylcholinesterase staining) in the frontal cortex reduced in aged BF-lesioned rats, but not in normal aged rats. The number of binding sites (Bmax) for [3H]vesamicol, a ligand for the vesicular acetylcholine transporter, in the frontal cortex of normal aged rats was significantly less than that in young adult rats, while the Bmax of aged BF-lesioned rats was higher than that of normal aged rats. The levels of monoamines and their metabolites in the frontal cortex and striatum but not hippocampus of aged BF-lesioned rats were markedly reduced as compared with those of normal aged and young adult rats. These results taken together indicate that normal aged and aged BF-lesioned rats exhibit learning deficits and that the differences of the severity of spatial learning deficits between normal aged and aged BF-lesioned rats may be due to, at least in part, the different properties of cathecolaminergic, serotonergic and cholinergic dysfunctions in the discrete brain sites.

Topics: Acetylcholinesterase; Aging; Animals; Aziridines; Cerebral Cortex; Choline; Choline O-Acetyltransferase; Coloring Agents; Kinetics; Male; Maze Learning; Neuromuscular Blocking Agents; Piperidines; Prosencephalon; Rats; Rats, Inbred F344; Space Perception