Detail of "53179-11-6"

Reference

Loperamide: blockade of calcium channels as a mechanism for antidiarrheal effects

Loperamide: blockade of calcium channels as a mechanism for antidiarrheal effects. Reynolds, Ian J.; Gould, Robert J.; Snyder, Solomon H. (Sch. Med., Johns Hopkins Univ., Baltimore, MD, USA). J. Pharmacol. Exp. Ther., 231(3), 628-32 (English) 1984. CODEN: JPETAB. ISSN: 0022-3565. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) The antidiarrheal opiates loperamide (I) [53179-11-6], fluperamide [53179-10-5], diphenoxylate [915-30-0], and fetoxylate [23607-71-8] inhibited binding of [3H]nitrendipine to membranes from guinea pig cerebral cortex with Ki values of 0.5-10 mM. Loperamide and fluperamide reversed the tiapamil-elicited lowering of [3H]nitrendipine binding with IC50 values of 0.2-0.5 mM, indicating a verapamil-like action of these drugs. An oral dose of 1 mg/kg of loperamide reduced gastrointestinal motility and gave concns. of 0.45, 0.38, and 0.49 mM in the duodenum, jejunum, and ileum, resp. The apparent Ki for loperamide in preventing Ca-induced contractions of guinea pig ileum depolarized with 80 mM K was 0.10 mM. Ca channel antagonism may be responsible, at least in part, for the antidiarrheal actions of loperamide and related agents. Supporting evidence includes the Ca antagonist actions of loperamide at antidiarrheal doses, the constipating effects of certain Ca antagonists, and the failure of opiate antagonists to prevent some intestinal effects of loperamide.

Effect of dextromethorphan on guinea pig ileal contractility in vitro: comparison with levomethorphan, loperamide and codeine

Effect of dextromethorphan on guinea pig ileal contractility in vitro: comparison with levomethorphan, loperamide and codeine. Kachur, James F.; Morgan, Douglas W.; Gaginella, Timothy S. (Dep. Pharmacol. Chemother., Hoffmann-La Roche Inc., Nutley, NJ, USA). J. Pharmacol. Exp. Ther., 239(3), 661-7 (English) 1986. CODEN: JPETAB. ISSN: 0022-3565. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Dextromethorphan (DM) [125-71-3] was tested for its effects on the contractility of the guinea pig ileum in vitro. Comparison were made with levomethorphan [125-70-2], levorphanol [77-07-6], codeine [76-57-3] and loperamide [53179-11-6]. DM and codeine inhibited the contractions of the elec. stimulated ileum with IC50 values of 15 and 8 mM, resp. The inhibitor effect of DM, in contrast to codeine, was not blocked by the opiate antagonist naloxone. Pretreatment (8, 50 and 100 mM) with DM and its l-isomer levomethorphan reduced in a dose-dependent fashion both phasic and tonic contractions produced by maximally effective concns. of carbachol [51-83-2] and 80 mM KCl. Pretreatment (8, 50 and 100 mM) with codeine, dextrorphan or levorphanol, unlike DM, did not reduce carbachol or KCl-induced contractions. The concn.-response curves to Ca2+ in K+ depolarized ileum were shifted to the right in a parallel manner, suggesting competitive antagonism for DM (pA2 5.3), levomethorphan (pA2 5.3) and loperamide (pA2 6.6). Codeine and levorphanol (8, 50 and 100 mM) did not antagonize Ca2+-induced contractions. In 2 assays of calmodulin-dependent processes, DM was inactive (IC50 > 1 mM), whereas trifluoperazine and calmidazolium (std. calmodulin antagonists) were active in the micromolar range. In summary, these data suggest that DM, through a nonopiate mechanism, antagonizes gut contractility possibly by "stabilizing" neuronal and/or muscle cell membranes.