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• W2068711231 startingPage "549" @default.
• W2068711231 abstract "Described are the synthesis and some aspects of the pharmacology of acetylseco hemicholinium-3 (acetylseco HC-3), the acetylated open ring analogue of hemicholinium-3 (HC-3). The effects of both compounds were determined in vivo on rat brain acetylcholine (ACh), 14C-eholine (14C-Ch) incorporation into 14C-acetylcholine (14C-ACh) and on one way jump box avoidance and escape behavior in naive and trained rats. In addition, the in vitro effects of both drugs were determined on choline acetyltransferase activity (ChAc) in rat brain. When given intraventricularly in doses of 1–20 μg both compounds reduced total ACh content in the brain to a maximum of 50% of normal in 30–60 min. In doses of 20 μg intraventricularly, both drugs also reduced 14C-Ch incorporation into 14C-ACh by 84.5% for acetylseco HC-3 and by 52% for HC-3. The in vivo changes of ACh in the brain were correlated with the behavioral deficits induced in one way shuttle box acquisition and retention. In doses of 20 μg total intraventricularly, both compounds produced behavioral deficits which were greater in naive than in trained animals. In vitro, acetylseco HC-3 inhibited ChAc activity with an I50 of 1 × 10−5m with Ch 10−2m and acetyl CoA 6.4 × 10−4m, while HC-3 had no inhibitory effects. Using rat brain homogenate as the enzyme source and commercial acetyl CoA for kinetic studies, acetylseco HC-3 was shown to be a mixed inhibitor of acetyl CoA and a competitive inhibitor of Ch. The in vivo actions of acetylseco HC-3 are consistent with those of a ChAc inhibitor. However, it is necessary to rule out the possibility that the drug may also compete with Ch for its transport across biological membranes like its deacetylated derivative HC-3." @default.
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• W2068711231 date "1973-06-01" @default.
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• W2068711231 title "Acetylseco hemicholinium-3, a new choline acetyltransferase inhibitor useful in neuropharmacological studies" @default.
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• W2068711231 doi "https://doi.org/10.1016/0028-3908(73)90005-1" @default.
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