RESUMO
OBJECTIVE AND DESIGN: 1-(Carboxymethyl)-3,5-diphenyl-2-methylbenzene (CDB), a novel arylacetic acid, was evaluated in vivo for its ability to inhibit acute and chronic inflammation as well as acute pain. MATERIALS AND METHODS: The effects of CDB were evaluated using the following assays: 1) acute inflammation induced by the injection of carrageenan, bradykinin and serotonin into the subplantar region of the hind paw of rats; 2) chronic inflammation produced by the injection of Mycobacterium butyricum into the base of the tail of rats; 3) acute pain induced by the i.p. injection of phenyl-p-quinone into mice resulting in the production of writhes; 4) cyclooxygenase (COX) activity, including COX-1 and COX-2, evaluated using whole blood; and 5) activity of peptidylglycine alpha-monooxygenase (PAM) isolated from Xenopus laevis skin. RESULTS: CDB (10 to 100mg/kg s.c.) produced a dose-dependent inhibition of carrageenan edema (ED50 of 41 mg/ kg at 3 h) which continued for up to 12 h. Using a therapeutic dosing regimen, this compound inhibited hind paw inflammation (>70%) and arthogram scores in rats with adjuvant-induced arthritis. This compound also possessed significant analgesic activity in mice (70% inhibition with 50mg/kg). CDB, however, lacked inhibitory activity on bradykinin and serotonin-induced edema. In addition, CDB significantly inhibited COX-I activity (IC50 approximately = 17 microM) while having only a weak inhibitory activity on both COX-2 and PAM activity. CONCLUSIONS: CDB is an effective anti-inflammatory/analgesic agent whose mechanism of action appears to be associated with inhibition of COX-1 activity.
Assuntos
Acetatos/farmacologia , Anti-Inflamatórios não Esteroides/farmacologia , Benzeno/farmacologia , Inflamação/tratamento farmacológico , Complexos Multienzimáticos , Animais , Artrite Experimental/tratamento farmacológico , Bradicinina , Carragenina , Inibidores de Ciclo-Oxigenase/farmacologia , Edema/induzido quimicamente , Edema/tratamento farmacológico , Inibidores Enzimáticos/farmacologia , Pé/patologia , Inflamação/induzido quimicamente , Masculino , Camundongos , Oxigenases de Função Mista/antagonistas & inibidores , Medição da Dor/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Tempo de Reação/efeitos dos fármacos , SerotoninaRESUMO
4,5-Dimethylprimaquine and 5-fluoro-4-methylprimaquine were synthesized and evaluated against Plasmodium berghei in the mouse. Significant blood schizonticidal activity was observed. The 5-fluoro-4-methylprimaquine analog also was active as a tissue schizonticidal agent when evaluated against P. cynomolgi in the rhesus monkey, as an antileishmanial agent when evaluated against Leishmania donovani in the hamster, and as a causal prophylactic agent when evaluated against P. berghei yoelii.
