Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Proglumide”

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 73 records · Page 4Linked to original sources
PubMed1984

Proglumide: selective antagonism of the rumination but not gastric motor effects induced by pentagastrin in sheep.

The effect of intravenous (IV) vs intracerebroventricular (ICV) administrations of pentagastrin on gastro-intestinal motility and rumination were investigated by electromyography in sheep; these effects were compared to those obtained after a previous IV or ICV injection of proglumide. When ICV administered at a dose of 20 ng X kg-1, pentagastrin did not significantly affect the frequency of reticular and abomasal spiking activity but elicited a 13 to 37 min period of rumination after a delay of 23 +/- 7 min. In contrast, when IV infused at a rate of 20 ng X kg-1 X h-1 during 20 min, pentagastrin inhibited significantly the frequency of reticular and abomasal contractions for 30 to 40 min but did not induce rumination. Proglumide ICV administered (0.8 mg X kg-1) abolished the rumination induced by central injection of pentagastrin whereas a 10 times higher dose administered systemically (8 mg X kg-1 IV) did not block these effects. Both of ICV and IV administrations of proglumide at respectively 0.8 and 8 mg X kg-1 were unable to antagonize the inhibitory effects of pentagastrin on reticulum and abomasum motility. It was concluded that (i) pentagastrin acts centrally to induce rumination and that (ii) proglumide selectively blocks these effects but not the pentagastrin induced gastro-intestinal hypomotility.

Abomasum↗
PubMed1990

Cholecystokinin antagonists proglumide, lorglumide and benzotript, but not L-364,718, interact with brain opioid binding sites.

It has been reported that proglumide and L-364,718 potentiate opioid-induced antinociception. However, their mode of action in pain modulation is still not understood. To evaluate a possible interaction with opioid receptors, we determined the affinities of the CCK antagonists proglumide, lorglumide, benzotript and L-364,718 on mu, delta and kappa binding sites, using guinea pig brain crude synaptosome preparations. These affinities were compared to that of the central CCK binding site, using rat brain slide-mounted sections. At 100 microM, proglumide competed for 13% and 17% of mu and kappa binding sites, but did not interact with delta and CCK sites. At this concentration, lorglumide reduced mu, delta, kappa and CCK specific binding by 44%, 69%, 35% and 88%, whereas benzotript diminished it by 16%, 13%, 38% and 48%, respectively. L-364,718 did not interact with opioid receptors (assay limit of solubility, 10 microM) but had a high affinity for CCK binding sites (IC50, 126nM). The lack of selectivity of proglumide, lorglumide and benzotript for CCK receptors suggests that their reported ability to potentiate morphine analgesia may be related to an interaction with opioid receptors.

Animals↗
PubMed1986

Central and peripheral proglumide administration and cholecystokinin-induced satiety.

Peripheral (50 mg/ml) or central (50 micrograms/microliter) injections of proglumide were made into Sprague-Dawley rats which displayed satiety-like responses after the peripheral (100 micrograms/kg) or central (50 ng in 1 microliter) administration of cholecystokinin (CCK). The satiety produced by CCK injection into the lateral hypothalamus, area postraema and ventromedial hypothalamus was significantly reversed by proglumide injections into these areas during a 4 h food intake test. Peripheral injection of proglumide after central or peripheral CCK injection did not modify this type of CCK-induced satiety. Central proglumide injection produced a reliable decrease in water intake and this is compatible with previous findings which describe the stimulation of water intake after central gastrin administration. These results suggest that various central and peripheral mechanisms which are involved in the regulation of appetite may function independently as a 'failsafe' system.

Animals↗
PubMed1987

Effects of proglumide on pancreatic endocrine and exocrine function in healthy humans.

A comparative study was done on the pancreatic endocrine (insulin (IRI), human pancreatic polypeptide (hPP] and exocrine secretion (fluid volume, amylase output, bicarbonate output), before and after administration of proglumide. At the time of the test meal loading, plasma hPP and cholecystokinin (CCK) were also measured. During continuous i.v. administration of proglumide 750 mg and 1650 mg/h 30 min before CCK-8 (20 ng/kg) stimulation, no significant difference in the rise of plasma hPP level was observed, as compared with a single stimulus of CCK-8, nor were there any significant differences in the exocrine secretion. The values of hPP and CCK-8 under a load of test meal significantly elevated after a food load. Although hPP showed a significant inhibition with the administration of proglumide 1650 mg/h, plasma CCK-8 and blood sugar levels were not significantly different from control groups. Therefore, while proglumide has a very weak effect on the action of pancreatic endocrine function, it does have an inhibitory effect on pancreatic function, during physiological stimulation.

Adult↗
PubMed1988

Effects of gastrin, proglumide, and somatostatin on growth of human colon cancer.

The effects of gastrin, proglumide (a gastrin receptor antagonist), and somatostatin on growth of human colon adenocarcinoma cell lines CX1, X56, and HT29 were examined in two experimental models. Nude mice bearing xenografts of colon cancer CX1 or X56 were treated for 14-25 days subcutaneously with saline, pentagastrin (0.5 or 1.0 mg/kg), proglumide (250 or 500 mg/kg), or somatostatin 14 (33, 100, or 300 micrograms/kg) twice daily. Tumor volume, weight, protein, and deoxyribonucleic acid were measured. HT29 cells were grown in vitro and the effects of gastrin 17, proglumide, and somatostatin on growth were evaluated by cell counts or [3H]thymidine incorporation. The larger dose of pentagastrin significantly increased tumor growth in the nude mouse (p less than 0.005) and gastrin induced a biphasic effect on deoxyribonucleic acid synthesis in tissue culture with significant increases of up to 39% (p less than 0.025). Somatostatin alone significantly inhibited tumor growth in two of the cell lines and also inhibited the gastrin-induced growth. Proglumide had no effect by itself but significantly inhibited gastrin-stimulated growth. These findings suggest that growth of some human colon cancers may be hormone-dependent.

Adenocarcinoma↗
PubMed1981

Proglumide and benzotript: members of a different class of cholecystokinin receptor antagonists.

In dispersed acini from guinea pig pancreas, proglumide (DL-4-benzamido-N, N-dipropylglutaramic acid) and benzotript (N-p-chlorobenzoyl-L-tryptophan) caused a rightward shift in the dose--response curve for cholecystokinin-stimulated amylase secretion but did not alter the maximal increase in amylase secretion caused by cholecystokinin. At relatively low concentrations, proglumide did not alter the stimulation of enzyme secretion caused by secretagogues whose effects are mediated by adenosine 3'5'-monophosphate (e.g., vasoactive intestinal peptide or secretin) and did not alter the stimulation of enzyme secretion caused by secretagogues that have a mode of action similar to that of cholecystokinin but act through different receptors (e.g., bombesin, physalaemin, eledoisin, and ionophore A23187). There was a close correlation between the ability of proglumide or benzotript to inhibit binding of 125I-labeled cholecystokinin to its receptors on pancreatic acini and the abilities of these compounds to inhibit the action of cholecystokinin on enzyme secretion and on calcium outflux. These results indicate that proglumide and benzotript are members of a different class of cholecystokinin receptor antagonists.

Amylases↗
PubMed1987

Proglumide, a cholecystokinin receptor antagonist, exacerbates alloxan-induced diabetes mellitus in Swiss mice.

The effect of proglumide ((+/-)-4-benzamido-N,N-dipropyl-glutaramic acid), a gastrin and cholecystokinin receptor antagonist, has been studied on the fasting plasma glucose (FPG) and insulin levels in normal and alloxan-diabetic mice. In normal mice, proglumide, administered as a single oral dose or twice daily for five consecutive days, did not produce any alteration in those parameters. Injection of alloxan monohydrate (70 mg kg-1 i.v.) produced a significant decrease in plasma insulin and a significant elevation of FPG levels on the 5th day after its administration as evidence of diabetes mellitus. Proglumide sodium, given as a single acute dose on the 5th day of alloxan injection, or as a twice daily dose for 5 days immediately after alloxan injection, significantly exacerbated the hyperglycaemia and further decreased the plasma insulin levels thus worsening the diabetogenic effect of alloxan. These observations point to a possible involvement of cholecystokinin (CCK) in alloxan-induced diabetes and indicate a need for monitoring the levels of FPG in diabetic patients being treated with a high dose of proglumide or other CCK-antagonists.

Animals↗
PubMed1999

[The action of proglumide blocking gastrin on gastric cancer cells].

OBJECTIVE: To investigate the practicability of proglumide to treat gastric cancer. METHODS: MKN45 gastric cancer cell line was cultured and the effects on gastrin and gastrin receptor antagonist proglumide proliferative rate, cell dynamic cycle distribution and the concentration of cAMP in the cells were observed in vitro. RESULTS: Gastrin promoted the proliferation of MKN45 cells and shifted cells from phase G(0)/G(1) to phase S, G(2)/M as well as increased intracellular cAMP, while proglumide blocked these effects. CONCLUSIONS: Gastrin induces the proliferation and synthesis of DNA by its receptor. Proglumide may provide a new approach of non-cytotoxic treatment of gastric cancer.

Cell Cycle↗
PubMed1990

In vivo comparison of inhibition with proglumide and CR-1409 of cholecystokinin-induced pressure in the biliary tract of the guinea pig.

This study was done to compare the effects of two cholecystokinin antagonists, proglumide and CR-1409, on cholecystokinin-induced changes in intrabiliary pressure in vivo. We have substantially modified the constant infusion biliary manometry model, successfully used in large animals, to measure contractility of the gallbladder in guinea pigs. A silicone catheter for manometry was placed in the fundus of the gallbladder of an anesthetized guinea pig, and the biliary tree was constantly infused at 0.1 milliliter per minute with normal saline solution. The intraluminal pressure of the system was continuously recorded. The model was used to demonstrate a dose-response curve to bolus administration of exogenous cholecystokinin (0.01 to 1.0 nanomole per kilogram) and also to study the actions of proglumide, an antagonist to gastrin and cholecystokinin, and CR-1409, a newer, specific cholecystokinin antagonist, on cholecystokinin-induced contraction of the gallbladder of the guinea pig in vivo. Proglumide, at a dose of 5 millimoles per kilogram, completely abolished increases in intrabiliary pressure caused by cholecystokinin (0.5 nanomole per kilogram), whereas this effect was achieved by only 5 micromoles per kilogram of CR-1409. In both, there was full recovery from cholecystokinin antagonism within one hour. CR-1409 is one thousand times more potent than proglumide against cholecystokinin-induced changes in intrabiliary pressure in vivo and appears to be a useful pharmacologic reagent to study cholecystokinin-mediated components of physiologic contraction of the gallbladder.

Animals↗
PubMed1989

Failure of proglumide, a cholecystokinin antagonist, to potentiate clinical morphine analgesia. A randomized double-blind postoperative study using patient-controlled analgesia (PCA).

The potential clinical utility of drug interactions between morphine and the cholecystokinin antagonist proglumide was examined in 80 postoperative patients suffering from moderate to severe pain. Four groups of ASA I-III patients (mean age 51 years, mean weight 72 kg) recovering from major abdominal or gynecological surgery (mean duration of surgery 141 minutes) performed under balanced anesthesia (midazolam, droperidol, fentanyl, N2O, enflurane) were randomly assigned to self-administer morphine-proglumide mixtures on the first postoperative day (ODAC; morphine demand dose 3 mg; infusion rate 0.36 mg/hr; lockout time 2 minutes; hourly maximum dose 15 mg/hr; proglumide doses per demand 0, 50 micrograms, 100 micrograms, or 50 mg). Morphine consumption, actual as well as retrospective pain scores (0-5) and side effects were evaluated. Mean duration of patient-controlled analgesia (PCA) in the subgroups was 17-19 hours, during which time 24.6 +/- 9.5 to 28.0 +/- 3.4 micrograms morphine.kg-1.hr-1 was given. There were no statistically significant differences between the groups either for drug consumption, pain scores, or side effects. It is therefore concluded that proglumide does not potentiate morphine analgesia in a clinical (postoperative) setting.

Adult↗
PubMed1987

Gastric and duodenal antiulcer and cytoprotective effects of proglumide in rats.

Proglumide has been studied for its ability to inhibit gastric secretion and to protect the gastroduodenal mucosa against the injuries caused by pyloric ligation, hypothermic restraint stress, acetic acid, nonsteroid anti-inflammatory drugs, reserpine, cysteamine and the cytodestructing agents: 80% ethanol, 0.6 M HCl, 0.2 M NaOH, 25% NaCl and 30 mg of acetylsalicylic acid in 0.35 M HCl in rats. The results of this study demonstrate that proglumide has both prophylactic and curative effects on various experimentally induced ulcers. It produced a dose-dependent inhibition of gastric secretion in the pylorus-ligated rats and reduced significantly the intensity of gastric lesions induced by pyloric ligation, hypothermic restraint stress, acetic acid, mucosal damaging agents and that of duodenal ulcers induced by cysteamine. The intensity of gastric lesions induced by nonsteroid anti-inflammatory drugs and reserpine was also reduced significantly by proglumide. Cimetidine, which was used as a standard antiulcer drug for comparison, also produced a similar protective effect in most of the models used by us. It was found to have a more potent antisecretory effect but failed to protect the rats against the gastric mucosal damage induced by hyperthermic restraint stress and 0.2 M NaOH. Our findings suggest that proglumide exerts these antiulcer effects by its antisecretory, gastric mucosal resistance increasing and cytoprotective activities. Further studies are required to find out its exact mechanism of action and therapeutic usefulness.

Animals↗
PubMed1985

Cholecystokinin-8 and proglumide modulation of electrically elicited eating.

Electrical stimulation of the lateral hypothalamus (ESLH) elicits eating reliably in satiated animals of many species. The time course of CCK-8 suppression of ESLH induced ingestion has been studied in rats using this central stimulus to elicit eating well beyond limits imposed by the onset of normal satiety in food deprived animals. The reversal of this CCK-8 suppression by the putative CCK-8 antagonist proglumide as well as the effects of proglumide itself upon electrically elicited eating have also been examined. It was found that the suppression of ESLH-induced eating by CCK-8 was potent, rapid in onset, and that its magnitude and duration were dose-related. Other results suggest that proglumide acts as an antagonist of exogenous CCK-8 best at lower doses, as at higher doses it may act as a mixed CCK-8 agonist-antagonist; however, proglumide may also have modulated electrically elicited eating by its effects upon central dopaminergic and/or opioid systems.

Animals↗
PubMed1984

Proglumide antagonizes the stimulation of rabbit gallbladder by cholecystokinin.

Proglumide (3 X 10(-4) to 3 X 10(-3) M) produced parallel rightward shifts in the cumulative concentration-response curves for cholecystokinin octapeptide (CCK-8) in the rabbit gallbladder. Contractile responses to acetylcholine and serotonin were inhibited noncompetitively by the highest concentration of proglumide tested. K+-induced contractions, however, were unaffected by proglumide. The results indicate that proglumide may be used as a selective, competitive antagonist of the actions of CCK-8 in the isolated rabbit gallbladder preparation.

Acetylcholine↗
PubMed1989

Loxiglumide. A new proglumide analog with potent cholecystokinin antagonistic activity in the rat pancreas.

D,L-4-(3,4-dichlorobenzoylamino)-5-(N-3-methoxypropyl-pentylami no)-5- oxopentanoic acid (CR 1505; loxiglumide) is a newly developed analog of proglumide. We examined the inhibitory effects of loxiglumide on pancreatic exocrine function in the isolated pancreatic acini and the isolated perfused pancreata of rats. Loxiglumide inhibited cholecystokinin octapeptide (CCK-8)-stimulated amylase release and, similarly, binding of [125I]CCK-8 to isolated rat pancreatic acini. Loxiglumide was about 3000 times more potent than the reference substance proglumide, but was about 1000 times less potent than L-364,718, another new CCK antagonist having benzodiazepine ring, in inhibiting CCK-8-stimulated amylase release. The inhibitory effect of loxiglumide displayed competitive kinetics and was specific for CCK in that the effects of other receptor secretagogues or agents bypassing receptors were not altered. The inhibitory effect of loxiglumide was fully reversible in isolated acini. However, the pancreata perfused with 10 microM loxiglumide for 20 min did not respond to CCK-8 for more than 20 min even after the removal of loxiglumide infusion. In contrast, an immediate increase in pancreatic exocrine secretion was observed after proglumide removal. Loxiglumide appeared to be bound to the receptors on acinar cells in a slowly dissociating state. These results indicate that loxiglumide acts as a potent, competitive, and specific CCK antagonist on the exocrine pancreas and, because of its prolonged inhibitory action, may be useful as a therapeutic agent in pancreatic disease.

Amylases↗
PubMed1985

Potentiation of morphine analgesia by the cholecystokinin antagonist proglumide.

Recent evidence has suggested that cholecystokinin (CCK) may act as a physiological opiate antagonist. Both the overlap of CCK and opiate systems within the central nervous system and the fact that exogenous CCK can antagonize opiate analgesia suggest that endogenous CCK systems interact with opiate-mediated pain inhibitory systems. In the present series of experiments, we examined the effect of the CCK receptor antagonist proglumide on various forms of morphine analgesia. We have observed that proglumide can potentiate morphine analgesia following systemic, intrathecal or intracerebral administration of these drugs. Endogenous CCK systems do not appear to be tonically active since neither systemic, intrathecal nor intracerebral proglumide typically produced measurable analgesia in the absence of morphine. These data suggest that CCK may be released in response to opiate administration and acts to return the organism toward its basal level of pain sensitivity. If such a hypothesis is in fact true, then CCK blockade may be of clinical value in the treatment of pain.

Analgesia↗
PubMed1987

Proglumide has access to brain and antagonizes the central satiety effect of cholecystokinin octapeptide in the dog.

Intra-third cerebroventricularly administered cholecystokinin octapeptide (CCK-8) decreased food intake through central mechanisms in the dog. Proglumide, administered intravenously, did enter into cerebrospinal (ventricular) fluid, and partially, but significantly, reversed this effect. CR1409, one of the newly synthesized glutaramic derivatives, blocked CCK-8-induced satiety more strongly than proglumide. These results indicate that systemic proglumide and CR1409 result in antagonism of the central CCK receptor for satiety in the dog.

Animals↗
PubMed1985

Potentiation of beta-endorphin effects by proglumide in rats.

The effects of proglumide, a cholecystokinin (CCK) receptor antagonist, on the analgesia and catalepsy induced by beta-endorphin were investigated in rats. Proglumide itself produced a slight analgesia but no catalepsy. Combined intracerebroventricular administration of beta-endorphin and proglumide produced marked potentiation of the analgesic and cataleptic effects of beta-endorphin. The results suggest that endogenous CCK may have an antagonistic effect on the actions of beta-endorphin in the brain.

Analgesia↗
PubMed1985

Chronic proglumide increases [3H]spiperone binding in the rat brain.

The cholecystokinin (CCK) antagonist, proglumide, administered chronically (41.0-53.5 mg/kg per day, 14 days) to rats via osmotic mini-pumps, produced a significant 13% increase in the number of [3H]spiperone labeled binding sites (Bmax) in the striatum. There was no associated change in the affinity (Kd) of [3H]spiperone for the striatal binding sites. Given chronically at lower dose levels (10.4-13.6 or 21.8-29.8 mg/kg per day), or acutely in doses of 10, 20 or 40 mg/kg s.c., proglumide failed to alter the binding of [3H]spiperone to rat striatal tissue. These data indicate long-term proglumide administration increases the number of binding sites for [3H]spiperone, thought to be a ligand for dopamine D-2 receptors.

Animals↗