Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Antidiarrheals”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 127 records · Page 7Linked to original sources
PubMed2000

Effect of zaldaride maleate, an antidiarrheal compound, on 16,16-dimethyl prostaglandin E2-induced intestinal ion secretion in rats.

The effect of zaldaride, a calmodulin inhibitor, on 16,16-dimethyl prostaglandin E2 (dmPGE2)-induced intestinal ion secretion was investigated in rats. Zaldaride inhibited the dmPGE2-induced increase in water content in the colon, but not that in the small intestine. In the colonic mucosa, zaldaride attenuated the dmPGE2-induced short-circuit current; however, it did not affect the forskolin or dibutyryl cAMP-induced effect. These results suggest that zaldaride inhibits dmPGE2-induced intestinal ion secretion by reducing the activity of Ca2+/calmodulin-dependent adenylate cyclase linked to a receptor, and the colon may be an important site in the action of zaldaride.

16,16-Dimethylprostaglandin E2↗
PubMed2000

Effects of zaldaride maleate, an antidiarrheal compound, on intracellular Ca2+-mediated short-circuit current response in the rat colonic mucosa.

The effect of zaldaride maleate (ZAL) on intracellular Ca2+-mediated short-circuit current (Isc) response in rat colonic mucosa was investigated. The Isc response to acetylcholine was partially reduced by the neuronal blocker tetrodotoxin. The tetrodotoxin-sensitive Isc response to acetylcholine was inhibited by ZAL. The tetrodotoxin-insensitive effect, which indicates direct stimulation of acetylcholine in colonic mucosa, was not affected by ZAL. The Isc response to the Ca2+ ionophore A23187 was reduced by ZAL in the presence of tetrodotoxin. These results suggest that ZAL reduces colonic ion secretion by inhibiting a tetrodotoxin-sensitive neuronal pathway and an intracellular Ca2+ pathway in epithelium.

Acetylcholine↗
PubMed2006

CFTR chloride channel drug discovery--inhibitors as antidiarrheals and activators for therapy of cystic fibrosis.

The Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) is a cAMP-activated chloride channel expressed in epithelia in the lung, intestine, pancreas, testis and other tissues, where it facilitates transepithelial fluid transport. In the intestine CFTR provides the major route for chloride secretion in certain diarrheas. Mutations in CFTR cause the hereditary disease cystic fibrosis, where chronic lung infection and deterioration in lung function cause early death. CFTR is a well-validated targeted for development of inhibitors for therapy of secretory diarrheas and activators for therapy in cystic fibrosis. Our lab has identified and optimized small molecule inhibitors of CFTR, as well as activators of DeltaF508-CFTR, the most common mutant CFTR causing cystic fibrosis. High-throughput screening of small molecule collections utilizing a cell-based fluorescence assay of halide transport yielded thiazolidinone and glycine hydrazide CFTR inhibitors that block enterotoxin-mediated secretory diarrhea in rodent models, including a class of non-absorbable inhibitors that target the CFTR pore at its external entrance. Benzothiophene, phenylglycine and sulfonamide potentiators were identified that correct the defective gating of DeltaF508-CFTR chloride channels, and other small molecules that correct its defective cellular processing. Small molecule modulators of CFTR function may be useful in the treatment of cystic fibrosis, secretory diarrhea and polycystic kidney disease.

Animals↗
PubMed1978

Toxicity studies on lidamidine hydrochloride (WHR-1142A), a novel antidiarrheal agent.

The acute oral LD50 of 1-(2,6-dimethylphenyl)-3-amidinourea hydrochloride (WHR-1142A, lidamidine hyrochloride) was 260 (208, 328) mg/kg in male mice, 267 (212, 336) mg/kg in male rats and 160 (130, 197) mg/kg in female rats. A daily oral dose of 10 mg/kg for 30 days was well tolerated in the rat and monkey. Histologic changes were reversible and for the most part could be explained on the basis of one or more of the several pharmacologic effects of WHR-1142A. A short-lived hyperglycemic effect was a prominent effect in mice and rats. This effect was seen occasionally in high doses in the monkey, suggesting a species difference.

Amidines↗
PubMed1978

Pharmacokinetics and disposition of lidamidine hydrochloride (WHR-1142A), a novel antidiarrheal agent, in rat and monkey.

14C-Labelled 1-(2,6-dimethylphenyl)-3-methylamidinourea hydrochloride (14C-WHR-1142A, lidamidine hydrochloride) was rapidly and quantitatively absorbed from the gastrointestinal tract of rat and monkey after a single oral dose of 5 mg/kg (base). Peak 14C levels occurred within 30 min and the radiolabel was found in both the plasma and cellular components of whole blood. The half-life of the parent compound was 30 min in rat and 1 h in the monkey. The label was essentially cleared from all tissues examined within 24 h in the rat. In both rat and monkey, the compound was extensively metabolized (greater than 90%) prior to excretion and eliminated primarily in the urine (95% of the 14C dose could be accounted for in urine within 24 h in the monkey and 65% within 24 h in the rat); about 15-20% of the dose was recovered in feces within 24 h in the rat. In rat, a significant portion of the dose was eliminated in bile, and enterohepatic recirculation of 14C excreted in bile occurred. In contrast, biliary elimination of 14C was not a major pathway in the monkey.

Amidines↗