A-4, a bis tertiary amine derivative of hemicholinium-3 produces in vivo reduction of acetylcholine in rat brain regions.

TitleA-4, a bis tertiary amine derivative of hemicholinium-3 produces in vivo reduction of acetylcholine in rat brain regions.
Publication TypeJournal Article
Year of Publication1987
AuthorsTedford CE, Schott MJ, Flynn JR, Cannon JG, Long JP
JournalThe Journal of pharmacology and experimental therapeutics
Volume240
Issue2
Pagination476-85
Date Published1987 Feb
ISSN0022-3565
Keywords3,4-Dihydroxyphenylacetic Acid; Acetylcholine; Animals; Brain Chemistry; Brain Mapping; Choline; Corpus Striatum; Dopamine; Hemicholinium 3; Hydroxyindoleacetic Acid; Norepinephrine; Rats; Serotonin
AbstractThe pharmacological effects of A-4, a bis 4-methylpiperidine tertiary amine derivative of hemicholinium-3, were investigated. Systemic administration (i.p.) of this compound produced a dose-dependent reduction in acetylcholine content of several brain regions. A dose of 40 mg/kg of A-4 produced a 40% reduction in acetylcholine content in the corpus striatum and this reduction was maintained for over 4 hr. Increased choline content was found concurrent with the reduction in acetylcholine content. Reversal of the A-4-induced reductions in acetylcholine content was seen with eserine and oxotremorine but not with choline chloride. Acute treatment with A-4 appeared selective for cholinergic neurons as no significant changes were seen in norepinephrine or serotonin parameters of any of the brain regions assayed. Dopamine turnover was increased in the striatum. The neurochemical changes produced by A-4 were not seen with the bis 4-methylpiperidine quaternary amine, A-5, or hemicholinium-3 after systemic administration of doses which produced pronounced behavioral and toxic effects. Intraventricular administration of A-5 or hemicholinium-3 produced a selective reduction in acetylcholine content. No changes were seen in dopamine, norepinephrine or serotonin parameters. Thus, A-4 represents a novel hemicholinium-3 analog in its ability to act centrally after systemic administration and may be potentially useful as a pharmacological tool in understanding cholinergic mechanisms in the central nervous system.
Alternate JournalJ. Pharmacol. Exp. Ther.