Abstract
Endogenous brain 5-hydroxyindoleacetic acid (5-HIAA) levels were markedly increased after mice received Sch 10595 [5-(n-butyl)-picohinamide], 100 mg/kg; the maximum increase was detected at 3 hours. Endogenous brain 5-hydroxytryptamine levels were elevated significantly at 1 and 2 hours. There was also a dose-related increase of 14C-5-HIAA formed from intracisternally injected 14C-5-hydroxytryptamine at 3 hours posttreatment. The increased levels of 5-HIAA after Sch 10595 treatment were not due to increased rate of 5-hydroxytryptamine synthesis or release. However, Sch 10595 was shown to impair efflux of 14C-5-HIAA from the mouse and rat brain, and the compound also elicited an increased level of acids in rat brain formed from intracisternally injected 14C-dopamine. This effect of Sch 10595 apparently does not relate to its dopamine-β hydroxylase inhibitory activity since two other dopamine-β-hydroxylase inhibitors, U-14, 624 and disulfiram, did not impair the efflux of acidic metabolites of catecholamines from the brain.
Footnotes
- Received November 3, 1973.
- Accepted May 2, 1974.
- © 1974 by The Williams & Wilkins Co.
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