THE EFFECT OF DIBENZAZEPINES (TRICYCLIC-ANTIDEPRESSANTS) ON CEREBRAL CAPILLARY-PERMEABILITY IN THE RAT INVIVO

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  • 1 January 1980
    • journal article
    • research article
    • Vol. 213  (2) , 313-320
Abstract
The degree of equilibration of [3H]water across the cerebral capillary was evaluated by measuring its cerebral extraction fraction (Ew) by using a dual label radioactive tracer tehcnique. All tricyclic antidepressants (125 .mu.mol/kg i.p. at 5 min) increased Ew as 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 induced a marked increase in the cerebral extraction fraction of [3H]ethanol (E). A difference in the time course of the drug effect on the 2 tracers indicated that the elevation in E was due to the increase in cerebral capillary permeability to both polar and lipid soluble substances. Tricyclic antidepressants have important central effects on non-neuronal tissue.