Suppression of the immune response by benzodiazepine receptor inverse agonists.
24 h after administration of a single dose of the benzodiazepine receptor inverse agonists N'-methyl-beta-carboline-3-carboxamide (FG 7142) and 3-carbomethoxy-4-ethyl-6,7-dimethoxy-beta-carboline (DMCM), a profound suppression of the immune response was observed in rodents. This immunosuppression was manifest as a decrease in phytohemagglutinin (PHA) and concanavalin-A (Con-A) stimulated T cell proliferation in rats and mice administered FG 7142 and a decrease in allogeneic cytotoxic T lymphocyte activity in mice administered either FG 7142 or DMCM. The effects of FG 7142 were antagonized by the prior administration of Ro 15-1788, a benzodiazepine receptor antagonist. These findings demonstrate that the neural pathways subserved by benzodiazepine receptors can modulate immune function, and suggest that these receptors may be involved in the stress-induced modulation of immune function.
D000818:Animals; D001067:Appetite Depressants / Q000494:pharmacology; D002243:Carbolines / Q000494:pharmacology*; D002478:Cells, Cultured; D003292:Convulsants / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D007165:Immunosuppression Therapy; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects / Q000276:immunology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D001067:Appetite Depressants; D002243:Carbolines; D003292:Convulsants; D011963:Receptors, GABA-A; C034818:methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate; C035874:FG 7142