Analgesic and anti-inflammatory effects of 3-[3-(phenyl)-1,2,4-oxadiazol-5-yl] propionic acid.

Significant local analgesic and anti-inflammatory activity has been observed after oral administration of 3-[3-(phenyl)-1,2,4-oxadiazol-5-yl] propionic acid (POPA). Doses of 150 and 300 mg/kg body weight administered orally by gavage to adult (25-35 g) albino mice of both sexes can inhibit acetic acid-induced writhing by 31.0% and 49.5%, respectively (mean +/- SEM writhing numbers during 20 min were 52.0 +/- 6.0 and 38.3 +/- 7.2 vs 75.8 +/- 6.6 for control group which received saline; N = 6). Carrageenin-induced inflammation in the female Wistar rat (200-250 g) can be reduced by 43.3% and 42.2% 3 h after oral administration (gavage) of 75 and 150 mg/kg of POPA (mean +/- SEM, 30.0 +/- 1.3% and 30.6 +/- 2.4% vs 52.9 +/- 3.7% for control group which received saline; N = 5). In the hot plate test on adult albino mice (25-35 g) of both sexes, POPA (150 and 300 mg/kg, po) was totally ineffective (N = 10). Our results indicate that POPA appears to offer potential safety and efficacy as a local analgesic and anti-inflammatory agent with no central nervous system involvement

Synthesis, anti-inflammatory and antimicrobial activities of new 1,2,4-oxadiazoles peptidomimetics.

A new series of 1,2,4-oxadizoles 6a-g have been synthesised in good yields using the peptide synthesis strategy. The prepared compounds were tested for anti-inflammatory and antimicrobial activities. The anti-inflammatory activities were determined in the rat paw oedema induced by carrageenin. Compounds 6a, c, f and g (i.v.) significantly inhibited the rat paw oedema induced by carrageenin depending upon the dose employed. The compounds were also evaluated for their in vitro antimicrobial activity. Some compounds were found to have significant activity against Gram positive and Gram negative microorganisms.

Antiinflammatory and chronic toxicity study of the leaves of Ageratum conyzoides L. in rats.

The hydroalcoholic extract (HAE) of Ageratum conyzoides leaves was studied for its antiinflammatory effect on subacute (cotton pellet-induced granuloma) and chronic (formaldehyde-induced arthritis) models of inflammation in rats. The absence or presence of toxicity by prolonged use of HAE was also evaluated through biochemical and hematological analysis of rats blood samples using daily oral doses of 250 or 500 mg/kg body wt., during 90 days. The results showed that the group of rats treated with HAE (250 mg/kg body wt.; p.o.) had a 38.7% (p < 0.05) reduction in cotton-pellet granuloma. The development of chronically induced paw edema was also reduced significantly (p < 0.05) by the plant extract. The toxicity study did not show any treatment-related abnormalities in biochemical and hematological parameters. The biochemical analysis from blood samples drawn from group of rats treated orally with 500 mg/kg body wt. did, however, present 30.2% (p < 0.05) reduction of SGPT activity as compared to the corresponding control group. These results confirm the antiinflammatory properties of A. conyzoides, with no apparent hepatotoxicity.

Developmental changes in the biochemical and functional properties of endothelin receptors in rabbit renal pelvis.

OBJECTIVE: To examine the effect of age on the biochemical and functional properties, and regional distribution of endothelin (ET) receptors in the rabbit renal pelvis. MATERIALS AND METHODS: The properties of ET receptors in 6-week-old and 6-month-old male rabbit renal pelves were examined using isolated muscle-bath and radioligand receptor-binding techniques. RESULTS: ET-1 caused a significant increase in the contractile force in muscle strips from all regions of the renal pelvis from both age groups, with the following rank order: upper=middle>lower. The magnitude of the ET-1-induced contractile responses were similar in the lower pelvic regions in both ages, but the responses in the upper and middle regions were significantly greater in younger rabbits. ET-1 increased the frequency of spontaneous activity in a concentration-dependent manner in the upper and middle pelvic regions in both age groups, with significantly smaller ED50 values in the younger than in the older rabbits. In both age groups the lower pelvic region lacked spontaneous activity. The density of total ET receptors was higher in the upper and middle regions of the renal pelvis than in the lower renal pelvis of both ages, with the density in the upper and middle regions being greater in older than in younger rabbits. In all regions, ET subtype selective compounds inhibited [125I]ET-1, binding consistent with the predominance of the ETA receptor subtype, except in the lower region of the older rabbits, in which the densities of ETA and ETB subtypes were similar. In all regions, the younger renal pelvis contained a higher proportion of ETA receptors than in older tissues. Light microscopic autoradiographic data indicated the presence of ETA and ETB receptors in smooth muscle and epithelial cells, respectively. CONCLUSION: These data indicate the presence of regional differences in the density of ET receptors and in the contractile responses to ET-1 in rabbit renal pelvis, and that although older rabbit renal pelvis contains more total ET receptors than younger renal pelvis, the latter had a higher portion of the ETA receptor subtype and the younger tissues were more responsive to ET-1.

Age-related changes in contractile responses of rabbit lower urinary tract to endothelin.

PURPOSE: As there are significant amounts of endothelin (ET) receptors in the mammalian urinary tract, we investigated the pharmacological properties and localization of ET receptors in the rabbit lower urinary tract as a function of age. MATERIALS AND METHODS: The characteristics of ET receptors in bladder dome, trigone and urethra of 6 weeks and 6 months old male rabbits were determined using muscle bath and autoradiographic techniques. RESULTS: ET-1 produces significant contractile responses in smooth muscle strips from bladder dome, trigone, and urethra in both 6 weeks and 6 months old rabbits. Although there was no significant difference in the maximum contractile response of urethral muscle strips to ET-1 between 6 weeks and 6 months old rabbits, the maximum responses to ET-1 were higher in both bladder dome and trigone of 6 weeks than 6 months old rabbits. A selective ETA receptor antagonist, BQ 610, shifted the concentration response curve to ET-1 to the right without decreasing maximal contractile responses in all regions from both age groups, whereas a selective ETB receptor antagonist, IRL 1038, had no significant effect on the contractile response in these tissues. Autoradiographic studies indicate that both ET receptor subtypes are expressed in bladder dome, trigone, and urethra with the ETA subtype being located only in the smooth muscle layers and the ETB subtype being located in both the urothelial and smooth muscle layers. CONCLUSION: Our data indicate the presence of region- and age-dependent differences in the contractile properties of ET receptors in the male rabbit lower urinary tract. Although both ETA and ETB receptor subtypes are present in the smooth muscle layers, the ETA receptor is the sub-type that is primarily involved in the mediation of contractions.

Analgesic and anti-inflammatory effects of 3-3-(phenyl)-1, 2, 4-oxadiazol-5-yl propionic acid

Significant local analgesic and anti-inflammatory activity has been observed after oral administration of 3-[3-(phenyl)-1,2,4-oxadiazol-5-yl] propionic acid (POPA). Doses of 150 and 300 mg/kg body weight administered orally by gavage to adult (25-35 g) albino mice of both sexes can inhibit acetic acid-induced writhing by 31.0 and 49.5, respectively (mean +/- SEM writhing numbers during 20 min were 52.0 +/- 6.0 and 38.3 +/- 7.2 vs 75.8 +/- 6.6 for control group which received saline; N = 6). Carrageenin-induced inflammation in the female Wistar rat (200-250 g) can be reduced by 43.3 and 42.2 3 h after oral administration (gavage) of 75 and 150 mg/kg of POPA (mean +/- SEM, 30.0 +/- 1.3 and 30.6 +/- 2.4 vs 52.9 +/- 3.7 for control group which received saline; N = 5). In the hot plate test on adult albino mice (25-35 g) of both sexes, POPA (150 and 300 mg/kg, po) was totally ineffective (N = 10). Our results indicate that POPA appears to offer potential safety and efficacy as a local analgesic and anti-inflammatory agent with no central nervous system involvement