The effect of dibenzazepines (tricyclic antidepressants) on cerebral capillary permeability in the rat in vivo

S. H. Preskorn, B. K. Hartman, M. E. Raichle, H. Brent Clark

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

The degree of equilibration of [3H]water across the cerebral capillary was evaluated by measuring its cerebral extraction fraction (E(w)) by using a dual label radioactive tracer technique. All tricyclic antidepressants (125 μmol/kg i.p. at 5 min) increased E(w) compared to base line. the rank order of the drugs in producing this response was doxepin>amitriptyline>imipramine>nortriptyline>desmethylimipramine>protriptyline. The effect of amitriptyline, the prototype tricyclic for this study, was rapid in onset (maximal effect within 5 min), reversible (duration 15 min), dose-dependent and generalized throughout the brain. Amitriptyline also induced a marked increase in the cerebral extracton fraction of [3H]ethanol. A difference in the time course of the drug effect on these two tracers indicated that the elevation in E was due to the increase in cerebral capillary permeability to both polar and lipid soluble substances. This work demonstrates that tricyclic antidepressants have important central effects on non-neuronal tissue.

Original languageEnglish (US)
Pages (from-to)313-320
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume213
Issue number2
StatePublished - Jan 1 1980

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