In vitro interaction of quinidine with kaolin and pectin

The adsorption of quinidine onto kaolin was studied as a function of pH in aqueous solutions in which the ionic strength was adjusted to 0.1. The interaction of quinidine with pectin also was investigated in water and in phosphate buffer; the buffer pH and ionic strength were adjusted to 6.5 and 0.1, respectively. The in vitro results indicated that quinidine was adsorbed onto kaolin. At the highest concentration studied, the extent of adsorption increased from 3.64 mg of quinidine adsorbed/g of adsorbent at pH 2.4 to an average of 5.81 mg/g in the pH 5.5-7.5 range. In the presence of electrolytes, the interaction of quinidine with pectin was relatively small (3-13% bound) as compared to studies performed in water (66-90% bound). The data indicate that some quinidine may be adsorbed when this drug is administered concurrently with kaolin-pectin preparations.     

盐酸丁螺环酮对动物口腔粘膜的渗透性及其机理

目的　研究盐酸丁螺环酮对动物口腔粘膜的渗透性及渗透机理。方法　采用离体动物口腔粘膜的体外渗透试验方法,比较盐酸丁螺环酮对家兔、豚鼠、猪、羊和牛的口腔粘膜渗透性,考察药物浓度及溶液pH值的影响。结果　盐酸丁螺环酮对家兔口腔粘膜的渗透性最大,渗透速率随溶液pH值升高而增大,与药物浓度成正比。结论盐酸丁螺环酮通过口腔粘膜转运的方式为被动扩散,转运途径为穿过细胞途径     

盐酸西替利嗪抗组胺作用的研究

目的：研究盐酸西替利嗪的抗组胺作用。方法：采用离体豚鼠回肠试验、皮肤通透性试验及组胺性休克试验进行观察。结果：盐酸西替利嗪浓度为１０－８～５×１０－７ｍｏｌ·Ｌ－１时，能明显拮抗组胺所致的离体豚鼠回肠收缩反应，使量效曲线平行右移；盐酸西替利嗪给小鼠（０．０５～０．５ｍｇ·ｋｇ－１）、豚鼠（０．０６２５～０．２５ｍｇ·ｋｇ－１）口服给药时，能使组胺所致的皮肤蓝斑面积明显缩小（Ｐ＜０．０１），其作用程度与剂量有关；盐酸西替利嗪０．０６２５～０．５ｍｇ·ｋｇ－１给豚鼠口服时，可显著降低豚鼠组胺性休克的死亡率（Ｐ＜０．０５），延长休克潜伏期（Ｐ＜０．０１），使休克反应程度明显降低（Ｐ＜０．０１）。结论：盐酸西替利嗪具有抗组胺作用。     

Effect of mebeverine hydrochloride on jejunal motility and epithelial transport in the anesthetized ferret.

Previous in vitro and in vivo studies demonstrate that mebeverine, administered to isolated smooth muscle preparations or given intravenously, (i.v.), acts as an antispasmodic agent and may be useful in treating intestinal hypermotility. Whether mebeverine affects intestinal mucosal transport is, however, unknown. The aim of the present study was to characterize the effect of mebeverine on both small intestinal motor activity and electrogenic epithelial transport in the urethane anesthetized ferret. The effects of mebeverine were compared following i.v. and intrajejunal (i.j.) administration. Following both routes of drug administration mebeverine dose dependently inhibited jejunal motility, with the i.j. route being more potent. However, when administered i.v. but not i.j., the doses of mebeverine that inhibited jejunal motility also significantly reduced heart rate and arterial blood pressure. Mebeverine (0.1-10 mg/kg) administered i.v. had no significant effect on epithelial transport as measured by a change in transmural potential difference. However, when dosed i.j., mebeverine (0.1-10 mg/kg) induced a decrease in potential difference towards lower lumen negativity, which was suggestive of a decrease in fluid secretion or enhancement of absorption. In conclusion, the results confirm in vivo the antispasmodic effect of mebeverine and suggested that mebeverine can influence epithelial transport, probably in the direction of enhanced intestinal absorption.     

Determination and characterization of metronidazole–kaolin interaction

The needs for safe, therapeutically effective antidiarrheal combination continuously lead to effective treatment. When administered simultaneously, metronidazole–kaolin interactions have been reported by FDA but not studied. This paper is the first to study metronidazole–kaolin interactions. Adsorption isotherms of a metronidazole–kaolin antidiarrheal combination from aqueous solutions at an in vivo simulated pH conditions were obtained at 37 ± 0.5 °C. Langmuir constants for the adsorption are 10.8225, 41.3223 mg g⁻¹ and 11.60, 2.56 l g⁻¹ aimed at the monolayer capacity, and the equilibrium constant at pH 1.2 and 6.8, respectively. pH effect on adsorption of known concentration of metronidazole by kaolin was also studied over the range 1.2–8. A gradual increase in the adsorbed amount was noted with increasing the pH. Elution studies by different eluents showed that drug recovery from adsorbent surface was pH-dependent via competitive mechanism. The elution followed the sequence: 0.1 M HCl > 0.1 M NaCl > H₂O. Adsorption–desorption studies revealed physical adsorption. The equilibrium concentration of metronidazole decreased as the adsorbent concentration was increased in the systems.The dissolution profiles (USP) of commercially available tablets (Riazole® 500 mg) were obtained alone and in the presence of either (ORS®) rehydration salts and 9 or 18 g of kaolin powder. The percentage drug released versus time: 95.01% in 25 min, 101.02% in 30 min, 67.63% in 60 min, 60.59% in 60 min, respectively.The percentage drug released versus time was increased with ORS® due to common ion effect [Cl⁻], while, it was decreased with kaolin due to adsorption. The mechanism of reaction of Riazole® (500 mg) tablets in the different dissolution media, confirms with Korsmeyer–Peppas model.The interaction between metronidazole and kaolin was characterized by melting point determinations, differential scanning calorimetry analysis and infrared spectroscopy. The results obtained were suggestive of physical interaction between metronidazole and kaolin.     

The in vitro adsorption of some antibiotics on antacids.

The adsorption of oxytetracycline hydrochloride, tetracycline hydrochloride, doxycycline hyclate, triacetyloleandomycin, chloramphenicol, ampicillin, and cloxacillin sodium was studied on various antacids namely, magnesium trisilicate, magnesium oxide, calcium carbonate, bismuth oxycarbonate, aluminium hydroxide, and kaolin. The adsorption of the various antibiotics by milk was also tested as milk is frequently used as an antacid. Charcoal was included in the present study as a model adsorbent having a large hydrophobic surface. The adsorption of the various antibiotics on the different antacids and other adsorbents in most cases obeyed the Freundlich adsorption isotherm. Magnesium trisilicate and magnesium oxide showed the highest adsorptive capacity, relative to other antacids used, for most antibiotics. Calcium carbonate and aluminium hydroxide and intermediate power while kaolin and bismuth oxycarbonate had the least adsorptive power. Charcoal exhibited a marked adsorption for all antibiotics tested. Tetracyclines were found to be more highly adsorbed than other antibiotics studied. Triacetyloleandomycin and chloramphenicol had intermediate values. Ampicillin was only adsorbed to a slight extent while cloxacillin was not adsorbed on the antacids used. The extent of adsorption was correlated to the structure of both the adsorbent and adsorbate, the pH of the adsorbent suspension, and to the polarity of the antibiotic in such pH. The reversibility of the adsorption process was studied in different media and at pH values similar to those of the gastrointestinal tract. The extent of elution was found to be inversely proportional to the adsorptive capacity of the different adsorbents. In general, 0.0143 n NaHCO3 solution was found to possess higher eluting properties than 0.01 n HCl. An exception to this pattern was observed with tetracyclines adsorbed on aluminium hydroxide where the elution with acid resulted in a higher degree of desorption. Careful in vitro and in vivo testing of drug availability is advisable prior to the concomitant administration of antibiotics with antacids or other adsorbents.     

葛缕酮的气道扩张作用和呼吸道抗过敏作用

目的观察留兰香油中葛缕酮的气道扩张作用和对呼吸道介质的影响。方法用豚鼠药物引喘法、豚鼠离体气管片法、致敏豚鼠肺组织ＳＲＳ Ａ释放和拮抗ＳＲＳ Ａ、致敏豚鼠离体气管Ｓｃｈｕｌｔｚ Ｄａｌｅ反应法检测。结果葛缕酮对豚鼠药物性哮喘具有保护作用,灌胃给药延长５０％剂量为７６ｍｇ·ｋｇ－１,气雾给药为６３ｇ·Ｌ－１;对豚鼠离体气管有直接松弛作用,ｐＤ２值为４２７±００８,并有抗氨甲酰胆碱作用;能抑制致敏豚鼠肺组织ＳＲＳ Ａ的释放,ＩＣ５０为１８ｍｇ·Ｌ－１,拮抗ＳＲＳ Ａ收缩回肠的ＩＣ５０为２７ｍｇ·Ｌ－１,并能抑制致敏豚鼠离体气管的Ｓｃｈｕｌｔｚ Ｄａｌｅ反应。结论葛缕酮具有气道扩张作用和呼吸道抗过敏作用。     

盐酸戊乙奎醚对豚鼠离体回肠/结肠的解痉作用

目的　研究盐酸戊乙奎醚 (PHC)对豚鼠离体回肠 /结肠肌条的抑制收缩作用。方法　将豚鼠离体回肠 /结肠条悬吊于麦氏浴槽中 ,测量给药PHC后豚鼠离体肌条自主收缩及乙酰胆碱 (Ach)所致痉挛收缩的最大张力 ,计算抑制 5.0 %收缩的PHC的浓度。结果　PHC对豚鼠离体回肠 /结肠肌条的自主收缩有明显抑制作用 ,对乙酰胆碱 (Ach)所致的痉挛性收缩有明显的松弛作用。结论　PHC能有效地缓解离体回肠 /结肠的痉挛状态。     

Tricyclic antidepressants: potent blockade of histamine H1 receptors of guinea pig ileum.

Six tricyclic antidepressants were tested for their ability to antagonize histamine actions at histamine H1 receptors in a bioassay for these receptors (histamine-induced contractions of guinea pig ileum). All compounds were competitive antagonists with equilibrium dissociation constants in the range of 5.6 x 10(-11) M to 1.5 x 10(-7) M. Doxepin hydrochloride and amitriptyline hydrochloride were the most potent compounds of the series and may be the most potent antihistamines known. Antagonism at histamine H1 receptors by these compounds may explain their sedative effects.     

Effects of azelastine hydrochloride, a new antiallergic drug, on the gastrointestinal tract

Effects of 4-(p-chlorobenzyl)-2-(hexahydro-1-methyl-1H-azepin-4-yl)-(2H)-phthalazinone hydrochloride (azelastine hydrochloride), a new antiallergic drug, on the gastrointestinal tract were experimentally studied in comparison with diphenhydramine and clemastine. In the isolated guinea pig ileum, the dose-response curve for histamine was shifted to the right by 10(-8) mol/l of diphenhydramine, clemastine or azelastine to the same degree. Clemastine and azelastine reduced the maximum response in the dose-response curve, while diphenhydramine caused a parallel shift. In addition to the potent antihistamine action, azelastine at higher dose antagonized serotonin action and clemastine markedly inhibited the contractile responses of isolated intestinal preparations to acetylcholine and bradykinin. Azelastine and clemastine (50 mg/kg intraduodenally) reduced gastric secretion in pylorus ligated rats. Azelastine (5 mg/kg i.v.), clemastine (1 mg/kg i.v.) and diphenhydramine (1 mg/lg i.v.) depressed gastrointestinal motility in conscious rats. Biliary and pancreatic secretions of anesthetized rats were not affected by 1 mg/kg i.v. of azelastine or clemastine.     

Preparation of chitosan beads by simultaneous cross-linking/insolubilisation in basic pH. Rheological optimisation and drug loading/release behaviour.

A one-step procedure to prepare chitosan beads by simultaneous cross-linking with glutaraldehyde and insolubilisation in 1.5 M NaOH solution has been developed. The optimisation of the procedure was carried out by monitoring the evolution of the loss and storage moduli of chitosan solutions (1.5% (w/v), in acetic acid 0.2 M) in the presence of different proportions of glutaraldehyde. Increasing the chitosan molecular weight, glutaraldehyde concentration and/or process temperature from 20 to 37 degrees C, a reduction of time to reach the gel point was observed. The diameter of freshly prepared swollen beads was 3.2+/-0.4 mm and, after drying 0.48+/-0.18 mm. Swollen or previously dried beads were loaded with metronidazole by immersion in 0.1% (w/v), drug solution in a phosphate buffer pH 7.5, purified water, 0.2 M acetic acid or 0.1 M HCl. Beads synthesised at 37 degrees C experimented faster swelling than the ones prepared at 20 degrees C and even disintegrated in acetic acid. The amounts of metronidazole loaded (ranging from 1 to 286 mg/g dried beads) increased with swelling capacity of beads. The release studies carried out in 0.1 M HCl indicated that, regardless of the medium used to load the beads, all of them released the dose in less than 30 min. In summary, applying this one-step procedure and choosing the adequate glutaraldehyde proportion, it is possible to obtain particles of chitosan cross-linked with itself, which exhibit pH-sensitive swelling and which are able to release all the drug quickly into an acidic environment such as the stomach. The results obtained also highlight the importance of the pH of the medium for modulating the amount of drug loaded (it is remarkably greater at lower pHs) and the influence of temperature at which the beads are prepared on their tendency to disintegrate.     

Morphine and naloxone act similarly on glutamate-caused guinea pig ileum contraction.

Both morphine (M) and naloxone (NL) have been reported to have NMDA receptor blocking effects, regarded as the reason of opiate physical dependence development. On the other hand, glutamate (GLU) has been known to induce the contraction of isolated guinea pig ileum via acetylcholine release. Therefore, different concentrations of M or NL were investigated on the 1 mM GLU-induced contraction of isolated guinea pig ileum fixed at a resting tension of 1 g in isolated organ bath. The mean value (359.3 +/- 20 mg) of the GLU-elicited contraction force was significantly reduced (318.4 +/- 19.4) by 25 nM M concentration in the medium. Consequently, 500 and 750 nM M caused further decreases in a rather dose-dependent manner (270.8 +/- 17.4 and 167.8 +/- 16.5 mg, respectively). One micromolar M contraction nearly abolished (8.0 +/- 8.2 mg) the GLU-induced contraction. A similar effect was obtained with the naloxone concentrations of 10, 20, 40, and 50 microM. In addition, NL has been shown to elicit the contraction of the isolated M-dependent guinea pig ileum. In the present study, 20- and 30-microM NL concentrations in the bathing medium caused the contraction of the ileum made M-dependent by preincubation with M (333.0 +/- 32.4 and 309.5 +/- 17.7 mg, respectively). These contraction forces were significantly reduced when the NL concentration was increased to 40 microM. And, 50 microM NL concentration not only failed to induce contraction but caused a relaxation (-10.6 +/- 2.3) as well. The results were considered supporting evidence for the fact that both M and NL are NMDA receptor blockers.(ABSTRACT TRUNCATED AT 250 WORDS)     

Penetration-Enhancing Effect of Ethanolic Solution of Menthol on Transdermal Permeation of Ondansetron Hydrochloride Across Rat Epidermis

The aim of this investigation was to study the effect of an ethanol-water solvent system and ehtanolic solution of menthol on the permeation of ondansetron hydrochloride across the rat epidermis in order to select a suitable ethanol-water vehicle and optimal concentration of menthol for the development of a transdermal therapeutic system. The solubility of ondansetron hydrochloride in ethanol, water and selected concenetrtaion of ethanol-water vehicles (20:80 v/v, 40:60 v/v and 60:40 v/v) was determined. The effect of these solvent vehicles, containing 1.5% w/v of ondansetron hydrochloride, on the in vitro permeation of the drug was studied across the rat epidermis. The highest permeation was observed from 60% v/v of ethanol-water vehicle that showed highest solubilty. Hence, the hydroxypropyl cellulose (HPC) (2% w/w) gel formulations containing 1.5% w/w of ondansetron hydrochloride and selected concentrations of menthol (0, 2, 4, 8 and 10% w/w) were prepared using 60% v/v of ethanol-water vehicle, and subjected to in vitro permeation of the drug across rat epidermis. The transdermal permeation of ondansetron hydrochloride was enhanced markedly by the addition of menthol to HPC gel drug reservoir formulations. A maximum flux of ondansetron hydrochloride (77.85 ± 2.85 μ g/cm^2.h) was observed with a mean enhancement ratio of 13.06 when menthol was incorporated at a concentration of 8% w/w in HPC gels. However, there was no significant increase in the drug flux with 10% w/w menthol when compared to that obtained with 8% w/w of menthol in HPC gel formulations. The results suggest that 2% w/w HPC gel drug reservoir formulation, prepared with 60% v/v ethanol-water, containing 8% w/w of menthol provides an optimal transdermal permeation of ondansetron hydrochloride.     

粉防己碱对吗啡在离体豚鼠回肠中依赖性的作用

AIM: To evaluate the effects of tetrandrine (Tet) and nimodipine (Nim) on the morphine (Mor) withdrawal response in the isolated guinea pig ileum. METHODS: The withdrawal contracture was elicited by addition of naloxone (Nal) (1 mumol.L-1) to the isolated naive ileum incubated with Mor (3 mumol.L-1) at 37.5 degrees C for 4 h or to the ileum obtained from Mor-dependent guinea pig. RESULTS: When Nim (0.01, 0.05, and 0.1 mumol.L-1) or Tet (1, 10, and 50 mumol.L-1) was added 1 min before Nal in the naive ilea bathed in Krebs solution containing Mor, or when the ilea from Mor-dependent guinea pigs were incubated with Nim (0.01, 0.05, and 0.1 mumol.L-1) or Tet (1, 10, and 50 mumol.L-1) for 15 min, or when Nim (5 and 10 mg.kg-1, i.p.) or Tet (15 and 30 mg.kg-1, i.p.) was administered in vivo to Mor-dependent guinea pigs, the Nal-precipitated withdrawal contracture was significantly decreased in a dose-dependent manner. CONCLUSION: Tet and Nim, Ca2+ channel blockers, could inhibit the Nal-precipitated Mor withdrawal response in the isolated guinea pig ileum.     

Evidence for histamine and 5-hydroxytryptamine like effects of MK-212 on guinea pig ileum, taenia coli and rat fundus strip

MK-212 (1 x 10(-7)M -- 1 x 10(-5)M) produced dose-dependent contractions of guinea pig ileum, taenia coil and rat fundus strip. The responses to MK-212 in all three preparations were blocked competitively by cyproheptadine (1 x 10(-8)M) a 5-HT receptor antagonist. Mepyramine (1 x 10(-8)M)-H1 receptor antagonist also inhibited competitively the responses of guinea pig ileum and taenia coli to MK-212. However, it failed to block significantly the responses of rat fundus strip to MK-212. Metiamide (1 x 10(-6)M), propranolol (1 x 10(-6)M) or atropine (1 x 10(-6)M) did not produce any significant effects on MK-212 induced contractile responses of guinea pig ileum, taenia coli and rat fundus strip. Our findings suggest that MK-212 produces both 5-HT as well as histamine like effects on the guinea-pig ileum, taenia coli and rat fundus strip.     

蜂斗菜不同提取物对豚鼠离体回肠收缩的影响

目的 比较蜂斗菜不同提取物对豚鼠离体回肠收缩的影响。方法 采用豚鼠离体回肠实验,以组胺、乙酰胆碱不同激动剂为研究模型,比较蜂斗菜CO₂超临界提取物、80%乙醇提取物、80%乙醇提取物的不同极性提取物及乙酸乙酯提取物经硅胶柱层析分离获得的不同馏分对豚鼠离体回肠的收缩作用,计算各个提取物对豚鼠回肠收缩幅度的抑制率。结果 蜂斗菜不同提取物对组胺、乙酰胆碱所致的豚鼠离体回肠收缩有显著拮抗作用,其中乙酸乙酯提取物硅胶柱色谱的馏分抑制作用最强。结论 蜂斗菜不同提取物均能抑制组胺、乙酰胆碱引起的豚鼠离体回肠收缩作用,脂溶性成分抑制作用最强,其机制可能与M、H₁受体的抑制有关。     

Functional identification of β3‐adrenoceptors in the guinea‐pig ileum using the non‐selective β‐adrenoceptor antagonist (±)‐bupranolol

1 To clarify whether there is a species difference or a tissue difference in β₃‐adrenoceptors, the β₃‐adrenoceptors mediating relaxations to catecholamines ((–)‐isoprenaline, (–)‐noradrenaline and (–)‐adrenaline), a selective β₃‐adrenoceptor agonist BRL37344 and a non‐conventional partial β₃‐adrenoceptor agonist (±)‐CGP12177A (a potent β₁‐ and β₂‐adrenoceptor antagonist with a partial β₃‐adrenoceptor agonist property) were investigated in the guinea‐pig ileum. 2 Catecholamines and β₃‐adrenoceptor agonists induced concentration‐dependent relaxations of pre‐contracted strips of the guinea‐pig ileum. The rank order for their relaxing potency was (–)‐isoprenaline (pD₂: 7.60) > BRL37344 (7.05) > (–)‐noradrenaline (6.38) > (±)‐CGP12177A (6.25) > (–)‐adrenaline (6.07). 3 In the presence of the non‐selective β₁‐ and β₂‐adrenoceptor antagonist (±)‐propranolol (1 μM ), only small rightward shifts of the concentration–response curves (CRCs) to these agonists were observed and the rank order of potency of agonists was BRL37344 (pD₂: 7.00) > (±)‐CGP12177A (6.17) > (–)‐isoprenaline (6.01) > (–)‐noradrenaline (5.69) > (–)‐adrenaline (5.41). 4 In the presence of (±)‐propranolol (1 μM ), the additional presence of (±)‐bupranolol (3–30 μM ), a non‐selective β₁‐, β₂‐ and β₃‐adrenoceptor antagonist, caused a concentration‐dependent rightward shift of the CRCs to catecholamines and β₃‐adrenoceptor agonists. Schild plot analyses of (±)‐bupranolol against these agonists gave pA₂ values of 6.02 ((–)‐isoprenaline), 6.03 ((–)‐noradrenaline), 6.01 ((–)‐adrenaline), 6.56 (BRL37344) and 5.74 ((±)‐CGP12177A), respectively. All Schild plot slopes were not significantly different from unity. The pA₂ values of (±)‐bupranolol obtained for the guinea‐pig β₃‐adrenoceptors were about one log unit less than the values obtained for the rat β₃‐adrenoceptors and about two log units less than the values obtained for dog β₃‐adrenoceptors. 5 These results confirm that functional β₃‐adrenoceptors are present in the guinea‐pig ileum and that the relaxations of these agonists are mainly mediated via β₃‐adrenoceptors in this tissue. The differential antagonistic potency of (±)‐bupranolol may suggest that there is a species difference between the three species (guinea‐pig, dog and rat) in their β₃‐adrenoceptors.     

Release of an acetylcholine-like substance from guinea pig ileum by scorpion venom

Scorpion venom contracts the guinea pig ileum. Incubation of the venom with segments of ileum releases a muscle active substance having properties like acetylcholine. The amount of substance released depends on the concentration of venom, the time of incubation and pH. It is concluded that the contraction of the guinea pig ileum produced by the venom is indirect, through the release of an acetylcholine-like substance.     

Effect of ethacrynic acid on guinea pig ileum

The effect of ethacrynic acid on the motor function of guinea pig ileum was studied in vitro. Ethacrynic acid produced dose-related (5-160 microgram/ml) contractions in this tissue. Morphine, tetrodotoxin and sodium-free medium prevented the contractions while hexamethonium, diphenhydramine, methysergide or indomethacin did not. Atropine in a high concentration (0.1 microgram/ml) only inhibited the contractions. Ethacrynic acid inhibited the contraction of ileum induced by electrical stimulation of intramural nerves. This was not prevented by pretreatment with reserpine. Repeated exposure to ethyacrynic acid developed tachyphylaxis in contractile response. Inhibition of electrically elicited contraction of guinea pig ileum also diminished with repeated treatment. Ethacrynic acid (80-160 micrograms/ml) inhibited the peristaltic reflex of the guinea pig ileum. It is concluded that the excitatory effect of ethacrynic acid is most probably mediated by the release of neurotransmitter, however, the mechanism of the inhibitory effect remains to be elucidated.     

Pharmacological actions of a new antihypertensive drug, olmidine, on the gastrointestinal tract]

It has been reported that dl-2-(3,4-methylenedioxyphenyl)-2-hydroxyacetamide hydrochloride (Olmidine) shows an antihypertensive action through inhibition of the adrenergic transmission. The present experiment was an attempt to investigate the pharmacological actions of olmidine in the alimentary canal of rat, rabbit and guinea pig. We found that the salivary secretion of rabbit was unaffected by olmidine at a dose of 2 mg/kg i.v., but increased by approximately 3 times that of controls with 10 mg/kg i.v.. Volume of gastric juice, concentration of free HCl, total acidity and pH of gastric juice in Shay rats were unaffected by 20 mg/kg i.p. of olmidine while volume and free HCl were significantly reduced at a dose of 100 mg/kg i.p. of the drug. The pH of gastric juice showed an evident increase to 3.33. Total acidity, however, was unaffected. Bile secretion of rat was decreased by olmidine at a dose of 100 or 500 mg/kg i.p. in a dose-dependent manner. Olmidine did not induce any lesion of gastric mucosa of rats at a dose of 200 mg/kg p.o. or less. Movement of charcoal meal in the small intestine of rats was inhibited by olmidine at doses of 20 to 500 mg/kg p.o.. Olmidine caused a biphasic response, that is contraction followed by a relaxation,in the isolated guinea pig gastrointestinal tracts. The contractile response caused by olmidine was completely inhibited by pretreatment with atropine or scopolamine and converted to one of relaxation which was unaffected by a combined treatment with phentolamine and propranolol. Contractile responses caused by transmural stimulation were significantly potentiated by olmidine, while potentiation of the contractile responses caused by exogenously applied acetylcholine was only slight in the isolated gallbladder from guinea pig.