Comparison of two PBR ligands with classical antiinflammatory drugs in LPS-induced arthritis in rats.
The antinociceptive and anti-edematogenic effects of peripheral benzodiazepine receptor (PBR) ligands, Ro5-4864 (7-chloro-5- (4-chlorophenyl)-1,3-dihydro-1-methyl-2-H-1,4-benzodiazepine-2) and PK11195 (1-(2-chlorophenyl)-N-methyl-N(1-methylpropyl)-3-isoquinoline carboxamide), were studied in an experimental model of carrageenan/LPS -induced arthritis in rats. These effects were compared with those of indomethacin and dexamethasone. Both pre and post-treatments with PK11195 were found to be anti-edematogenic and antinociceptive. The lower dose (0.01 mg/kg) exhibited the higher anti-edematogenic effect. On the other hand, the higher dose (0.5 mg/kg) produced antinociception, but with a decreased anti-edematogenic effect. Ro5-4864 produced a negligible antinociception and anti-edematogenic effect as pretreatment, but a pro-edematogenic effect when given as post-treatment. Dexamethasone and indomethacin presented parallel and dose-dependent antinociceptive and anti-edematogenic effects. In conclusion, PK11195 can effectively diminish arthritic nociception and edema elicited by LPS, but probably by mechanisms different from those of dexamethasone or indomethacin. RO5-4864 seemed to have opposite effect on this model.
Bressan
Elisângela
E
Department of Pharmacology, Federal University of Santa Catarina, Rua Ferreira Lima, 82, 88015-420, Florianópolis, SC, Brazil.
Farges
Roseli C
RC
Ferrara
Pascual
P
Tonussi
Carlos R
CR
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy*; D001570:Benzodiazepinones / Q000627:therapeutic use*; D002351:Carrageenan / Q000494:pharmacology; D003907:Dexamethasone / Q000627:therapeutic use; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000188:drug therapy / Q000517:prevention & control; D006614:Hindlimb / Q000187:drug effects / Q000503:physiopathology; D007213:Indomethacin / Q000627:therapeutic use; D007546:Isoquinolines / Q000627:therapeutic use*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D010146:Pain / Q000188:drug therapy / Q000517:prevention & control; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A; D016896:Treatment Outcome
D000276:Adjuvants, Immunologic; D001570:Benzodiazepinones; D007546:Isoquinolines; D008070:Lipopolysaccharides; D011963:Receptors, GABA-A; C028513:4'-chlorodiazepam; D003907:Dexamethasone; D002351:Carrageenan; D007213:Indomethacin; C037850:PK 11195