The effect of dibenzazepines (tricyclic antidepressants) on cerebral capillary permeability in the rat in vivo.
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 technique. All tricyclic antidepressants (125 mumol/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 greater than amitriptyline greater than imipramine greater than nortriptyline greater than desmethylimipramine greater than 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 extraction 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.
D000639:Amitriptyline / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D001794:Blood Pressure; D001834:Body Water / Q000378:metabolism; D001921:Brain / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism*; D002199:Capillary Permeability / Q000187:drug effects*; D003984:Dibenzazepines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000378:metabolism; D005260:Female; D008297:Male; D051381:Rats; D013997:Time Factors
D000929:Antidepressive Agents, Tricyclic; D003984:Dibenzazepines; D000639:Amitriptyline; D000431:Ethanol