Ogane N

References (4)

Title : Cholinesterase inhibitor effects on extracellular acetylcholine in rat cortex - Messamore_1993_Neuropharmacol_32_745
Author(s) : Messamore E , Warpman U , Ogane N , Giacobini E
Ref : Neuropharmacology , 32 :745 , 1993
Abstract : A microdialysis technique was used to sample acetylcholine (ACh) from the cerebral cortex of conscious rats. We thus investigated the effects of systemically administered cholinesterase inhibitors (ChEI) such as physostigmine (300 micrograms/kg), heptylphysostigmine (5 mg/kg) and tetrahydroaminoacridine (tacrine, 5 mg/kg) on extracellular ACh levels. Baseline quantities of extracellular ACh could be detected, even in the absence of ChEI. Acetylcholine levels increased to 1100% over baseline within 30 min of physostigmine administration and returned to control levels after 1.25 hr. Heptylphysostigmine elicited a maximal increase of 1000% within 1.5 hr, and the effect persisted up to 9.5 hr. A 500% increase was observed 1.5 hr after tacrine administration, and ACh returned to control levels after 4 hr. Although the ACh effects observed in this study correlated with previously determined levels of acetylcholinesterase (AChE) inhibition, we conclude that measures of cortical AChE activity alone are not sufficient to predict extracellular ACh levels following systemic ChEI administration.
ESTHER : Messamore_1993_Neuropharmacol_32_745
PubMedSearch : Messamore_1993_Neuropharmacol_32_745
PubMedID: 8413838

Title : Preferential inhibition of acetylcholinesterase molecular forms in rat brain - Ogane_1992_Neurochem.Res_17_489
Author(s) : Ogane N , Giacobini E , Messamore E
Ref : Neurochemical Research , 17 :489 , 1992
Abstract : The effect of eight different acetylcholinesterase inhibitors (AChEIs) on the activity of acetylcholinesterase (AChE) molecular forms was investigated. Aqueous-soluble and detergent-soluble AChE molecular forms were separated from rat brain homogenate by sucrose density sedimentation. The bulk of soluble AChE corresponds to globular tetrameric (G4), and monomeric (G1) forms. Heptylphysostigmine (HEP) and diisopropylfluorophosphate were more selective for the G1 than for the G4 form in aqueous-soluble extract. Neostigmine showed slightly more selectivity for the G1 form both in aqueous- and detergent-soluble extracts. Other drugs such as physostigmine, echothiophate, BW284C51, tetrahydroaminoacridine, and metrifonate inhibited both aqueous- and detergent-soluble AChE molecular forms with similar potency. Inhibition of aqueous-soluble AChE by HEP was highly competitive with Triton X-100 in a gradient, indicating that HEP may bind to a detergent-sensitive non-catalytic site of AChE. These results suggest a differential sensitivity among AChE molecular forms to inhibition by drugs through an allosteric mechanism. The application of these properties in developing AChEIs for treatment of Alzheimer disease is considered.
ESTHER : Ogane_1992_Neurochem.Res_17_489
PubMedSearch : Ogane_1992_Neurochem.Res_17_489
PubMedID: 1528356

Title : Differential inhibition of acetylcholinesterase molecular forms in normal and Alzheimer disease brain - Ogane_1992_Brain.Res_589_307
Author(s) : Ogane N , Giacobini E , Struble RG
Ref : Brain Research , 589 :307 , 1992
Abstract : Molecular forms of acetylcholinesterase were studied in three brain regions from Alzheimer disease patients and non-demented, age-matched controls. In Alzheimer disease patients, the membrane-bound G4 form was decreased in frontal (-71%) and parietal cortex (-45%) and in the caudate-putamen (-47%) from control levels. We also found a decrease of aqueous-soluble acetylcholinesterase molecular forms in the aqueous-soluble acetylcholinesterase molecular forms in the caudate-putamen region. The effect of three clinically significant acetylcholinesterase inhibitors, heptyl-physostigmine, physostigmine and edrophonium, on aqueous-soluble acetylcholinesterase molecular forms of the caudate-putamen was investigated. Heptyl-physostigmine, a physostigmine analogue, showed preferential inhibition for the G1 form. On the contrary, edrophonium inhibited the G4 form more potently than the G1 form. Physostigmine inhibited both forms with similar potency. The clinical implications of selective acetylcholinesterase inhibitors are discussed.
ESTHER : Ogane_1992_Brain.Res_589_307
PubMedSearch : Ogane_1992_Brain.Res_589_307
PubMedID: 1393597

Title : Effects of a M1 muscarinic receptor agonist on the central cholinergic system, evaluated by brain microdialysis - Ogane_1990_Neurosci.Lett_114_95
Author(s) : Ogane N , Takada Y , Iga Y , Kawanishi G , Mizobe F
Ref : Neuroscience Letters , 114 :95 , 1990
Abstract : The effects of a novel M1-receptor agonist, AF102B (FKS-508; cis-2-methylspiro(1,3-oxathiolane-5,3')quinuclidine), on the central cholinergic system in vivo were evaluated by determination of acetylcholine (ACh) content in the rat brain after microwave irradiation and by measurement of ACh release with microdialysis perfusion in freely moving rats. Intraperitoneal administration of AF102B resulted in a significant decrease of ACh content in the brain, while AF102B produced an increase of in vivo ACh release. The present results suggest that ACh content in the brain after treatment with muscarinic agents may be related to the changes of ACh release, in which both M1 and M2 muscarinic receptors may be involved.
ESTHER : Ogane_1990_Neurosci.Lett_114_95
PubMedSearch : Ogane_1990_Neurosci.Lett_114_95
PubMedID: 2381577