Involvement of steroids in anti-inflammatory effects of peripheral benzodiazepine receptor ligands.
Mouse paw oedema induced by carrageenan is used to determine if glucocorticoids are involved in the anti-inflammatory effects of peripheral benzodiazepine receptor ligands. The anti-inflammatory responses elicited by i.p. treatment with 1-(2-chlorophenyl)-N-methyl-N (1-methyl-propyl)-3-isoquinoline carboxamide (PK11195) and 7-chloro-5-(4-chlorophenyl)-1,3-dihydro-1-methyl-2-H-1, 4-benzodiazepin-2 (Ro5-4864) were reversed by aminoglutethimide, an inhibitor of steroidal synthesis. Intraplantar injection into the ipsilateral paw of Ro5-4864, but not PK11195, inhibited the formation of paw oedema and this effect was reversed by aminoglutethimide. These results suggest that glucocorticoids are involved in the systemic and local anti-inflammatory effects of Ro5-4864 and only in the systemic response to PK11195.
Farges
Roseli C
RC
Department of Pharmacology, Centre of Biological Sciences, Universidade Federal de Santa Catarina, Rua Ferreira Lima, 82, Florianópolis, SC, 88015-420, Brazil. roseli.farges@wanadoo.fr
Torres
Sandra R
SR
Ferrara
Pascual
P
Ribeiro-do-Valle
Rosa M
RM
D000616:Aminoglutethimide / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents; D001570:Benzodiazepinones / Q000037:antagonists & inhibitors / Q000494:pharmacology; D002351:Carrageenan; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005528:Foot / Q000473:pathology; D007546:Isoquinolines / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008024:Ligands; D008297:Male; D051379:Mice; D010525:Peripheral Nerves / Q000187:drug effects*; D011963:Receptors, GABA-A / Q000187:drug effects*; D013256:Steroids / Q000502:physiology*
D000893:Anti-Inflammatory Agents; D001570:Benzodiazepinones; D004791:Enzyme Inhibitors; D007546:Isoquinolines; D008024:Ligands; D011963:Receptors, GABA-A; D013256:Steroids; D000616:Aminoglutethimide; C028513:4'-chlorodiazepam; D002351:Carrageenan; C037850:PK 11195