Antidiarrheal Compound Research Articles

Effects of loperamide on intestinal ion transport.

The synthetic opiate loperamide (LPMD) is an antidiarrheal compound which affects both intestinal motility and the transport of water and electrolytes. We have investigated its effects on ion transport in the stripped ileal mucosa of rabbits, mounted in Ussing chambers in vitro. Addition of LPMD to serosal bathing medium resulted in a dose-dependent decrement of short-circuit current (Isc). LPMD (50 microM) significantly increased net Cl absorption (JClnet) and JRnet (assumed to represent HCO3 secretion). LPMD also inhibited the Isc increments evoked either by agents that increase 3',5'-cyclic adenosine monophosphate (cAMP) content (theophylline and prostaglandin E2) or by the Ca2+ ionophore A23187; the opiate, however, did not prevent the Isc change induced by 3',5'-cyclic guanosine monophosphate (cGMP)-related agents such as 8-Br-cGMP and Escherichia coli heat-stable enterotoxin. LPMD did not alter basal or secretagogue-stimulated tissue cAMP. In contrast, LPMD caused a small increase in cGMP content of stripped ileal mucosa, but not in that of isolated enterocytes. The role of Ca2+ in LPMD action is suggested by the significantly different effect of the drug on JClnet in the presence and in the absence of Ca2+ in the serosal solution.

Absorption of salicylate and bismuth from a bismuthsubsalicylate-containing compound (Pepto-Bismol)

MANY OVER-THE COUNTER ANTIDIARRHEAL COMPOUNDS are commonly given to children with diarrhea in an attempt to alleviate symptoms. Bismuth subsalicylate has been an active ingredient in some products used for this purpose. It was thought that bismuth subsalicylate was not absorbed from the gastrointestinal tract; however, a study in adults 1 indicates that after hydrolysis of bismuth subsalicylate in the gastrointestinal tract, measurable concentrations of salicylate in serum are achieved. The purpose of this study was to evaluate the absorption of salicylate and bismuth following single and multiple oral doses of a bismuth subsalicylate-containing compound (Pepto-Bismol, NorwichEaton Pharmaceuticals) in children and adults. MATERIALS AND METHODS Patient selection. Two groups of volunteers were studied. Seven healthy male children (ages 6 to 7 years) received single or multiple doses of Pepto-Bismol according to label instructions; these children collected urine specimens and did not have blood drawn. Four healthy male adult volunteers (ages 32 to 37 years) ingested multiple does of PB and subsequently had blood specimens collected. The adults were used for the blood studies because of constraints on human experimentation in children. The studies were approved by the Committees for the Protection of Human Subjects at The University of Texas Medical School and the University of Houston. Children were enrolled after obtaining their assent and parental permission; adults gave their informed consent. All subjects had a history negative for aspirin sensitivity or bleeding disorders, were receiving no medications, and had received no~ aspirin or salicylate-containing compounds for at least seven days prior to study. Immediately before administration of PB, all children had urine tested for salicylate concentration.

Receptor affinity and pharmacological potency of a series of narcotic analgesic, anti-diarrheal and neuroleptic drugs

A series of 26 drugs was tested for in vitro binding to opiate receptors in the presence and absence of 0.1 M NaCl. The results were correlated with assays for in vivo pharmacological potency. Highly significant correlation was found between binding in the presence and absence of sodium ions and analgesic potency. For 10 drugs tested for anti-diarrheal potency significant correlation was observed with binding to brain opiate receptors when binding was carried out in sodium-containing medium. These data add support to the hypothesis that stereospecific opiate binding sites are pharmacological receptors which mediate analgesia and anti-diarrheal action. We found that neuroleptics can bind to opiate receptors with affinities in the micromolar range, in agreement with reports by others. The anti-diarrheal compound loperamide exhibits no significant central opiate effects but binds to opiate receptors from brain in vitro with high affinity. Evidence is presented suggesting that the lack of specific analgesic effect is the result of poor penetration through the blood-brain barrier. Our results lend further support to the similarity of opiate receptors in the brain and in the intestinal tract.