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.

SourceResearch connectionFrom yearThrough year

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

At least 91 records · Page 5Linked to original sources

PubMed1984

Proglumide prevents and curtails acute tolerance to morphine in rats.

The antagonism of the antinociceptive action of morphine elicited by CCK-8-SO4 can be counteracted by proglumide, a CCK antagonist. The addition of morphine (10(-6)M) to the artificial spinal fluid perfusing the subarachnoidal space of rat spinal cord increases the CCK content of the perfusate. Proglumide can potentiate morphine analgesia without changing the half life of morphine. After seven to eight subcutaneous injections of morphine (4 mg/kg) repeated every two hrs there is tolerance to the antinociceptive action of morphine. Proglumide can partially block or reverse this acute tolerance to morphine.

Animals↗

PubMed1991

Enhancement of phenylpropanolamine anorexia by proglumide in rats.

Although a number of studies have characterized the anorectic state induced by phenylpropanolamine (PPA), the mechanism by which this drug suppresses appetite remains elusive. PPA inhibits gastric emptying at doses that also suppress appetite as does the gut hormone cholecystokinin (CCK). To evaluate whether PPA anorexia results via an action on gut CCK activity, rats in the present study were treated (IP) with either 0.9% saline or 150 mg/kg proglumide, a CCK receptor antagonist, 30 minutes before a 15 min feeding trial and then injected (IP) 5 min prior to the trial with either 0.9% saline, 5 mg/kg PPA, 10 mg/kg PPA, 8 ug/kg CCK or 16 ug/kg CCK. Although 150 mg/kg proglumide antagonized CCK anorexia, this dose of proglumide significantly enhanced the anorectic action of PPA. These results suggest that PPA does not act via an endogenous CCK system to suppress feeding.

Analysis of Variance↗

PubMedDate not supplied

Cholecystokinin octapeptide, proglumide, and passive avoidance in rats.

Rats were conditioned to avoid a darkened chamber using electric footshock (0.25 mA for 2 sec). Cholecystokinin octapeptide (CCK-8), a CCK-8 antagonist proglumide, or 0.9% NaCl solution was injected immediately following the footshock to study the effect upon passive avoidance behavior. The passive avoidance behavior was observed one day following the conditioning footshock and treatment. CCK-8 produced a reduction of the passive avoidance latency of rats at doses ranging from 30 micrograms/kg to 500 micrograms/kg. Proglumide (5 mg/kg) was able to block the CCK-8 effect on rat passive avoidance conditioning. Proglumide by itself at a dose of 2 mg/kg decreased the latency to enter the darkened chamber. Endogenous CCK-8 activity may be involved in passive avoidance conditioning in rats.

Animals↗

PubMed1991

Inhibition of the analgesia inhibitory system by D-phenylalanine and proglumide.

Stimulation of a nonacupuncture point (NAPS) does not normally produce analgesia in the same way that stimulation of an acupuncture point does. However, NAPS did produce dexamethasone reversible analgesia after intraperitoneal treatment with D-phenylalanine (DPA) or proglumide, or after microinjection of these compounds into such parts of the analgesia inhibitory system (AIS) as the lateral centromedian nucleus of the thalamus and part of the posterior hypothalamus. Inhibition of acupuncture analgesia (AA), or of morphine analgesia (MA) by 0.5 mg/kg, IP, which is equivalent to AA after AIS lesion, and of potentials in the lateral periaqueductal central gray evoked by repetitive NAPS or stimulation of the AIS, were antagonized by DPA. Disappearance of AA and MA in morphine tolerant acupuncture responder and nonresponder rats was reversed to reproduce the same magnitude of analgesia after proglumide application. The reproduced AA and MA were antagonized by dexamethasone. These results indicate that DPA and proglumide antagonized the AIS and unmasked the dexamethasone reversible AA and MA.

Acupuncture Analgesia↗

PubMed2006

Naloxone, not proglumide or MK-801, alters effects of morphine preexposure on morphine-induced taste aversions.

Both cholecystokinin (CCK) antagonists and N-methyl-D-aspartate (NMDA) antagonists block or reduce the development of morphine tolerance in several analgesic assays. The present experiments were performed to assess the ability of the CCK antagonist proglumide and the NMDA antagonist MK-801 to affect tolerance to the aversive properties of morphine as indexed by conditioned taste aversion (CTA) learning. Specifically, male Sprague-Dawley rats were exposed to either vehicle or morphine (5 mg/kg) in combination with either proglumide (5 mg/kg; Experiment 1), MK-801 (0.1 mg/kg; Experiment 2) or naloxone (1, 3.2 mg/kg; Experiment 3). Saccharin was then presented and was followed by an injection of either vehicle or morphine (10 mg/kg). Animals preexposed to and conditioned with morphine acquired an attenuated morphine-induced aversion to saccharin. While neither proglumide nor MK-801 had an effect on this attenuation, naloxone blocked the effects of morphine preexposure, suggesting that neither CCK nor NMDA may be involved in the aversive effects of morphine (or their modulation by drug exposure). That the attenuating effects of morphine preexposure on a morphine-induced CTA can be blocked suggests that the weakening of the aversive effects of morphine with chronic use can be prevented, an effect that may have implications for overall drug acceptability.

Animals↗

PubMed1997

Blockade of nocebo hyperalgesia by the cholecystokinin antagonist proglumide.

In patients who reported mild postoperative pain, we evoked a nocebo response, a phenomenon equal but opposite to placebo. Patients who gave informed consent to increase their pain for 30 min received a substance known to be non-hyperalgesic (saline solution) and were told that it produced a pain increase. A nocebo effect was observed when saline was administered. However, if a dose of 0.5 or 5 mg of the cholecystokinin antagonist proglumide was added to the saline solution, the nocebo effect was abolished. A dose of 0.05 mg of proglumide was ineffective. The blockade of the nocebo hyperalgesic response was not reversed by 10 mg of naloxone. These results suggest that cholecystokinin mediates pain increase in the nocebo response and that proglumide blocks nocebo through mechanisms not involving opioids. Since the nocebo procedure represents an anxiogenic stimulus and previous studies showed a role for cholecystokinin in anxiety, we suggest that nocebo hyperalgesia may be due to a cholecystokinin-dependent increase of anxiety.

Analgesics, Non-Narcotic↗

PubMed2002

Resolution of (RS)-proglumide using lipase from Candida cylindraceae.

Proglumide is used in the treatment of neuropathic pain. It acts by inhibiting peptide cholecystokinin (CCK). Neural injury produces an elevation in plasma CCK. Proglumide has been also shown to augment the analgesic effect of sustained release morphine in neuropathic pain. Currently proglumide is administered as a racemic mixture. In the present study, an attempt is made to separate the racemic mixture of the drug using lipase obtained from Candida cylindracea by stereoselective esterification. Enzymatic stereoselective esterification was carried out in organic solvents. The resolution was studied using a chromatographic column with a chiral support and mass spectrometry. The reaction conditions for stereoselective esterification including amount of substrate, amount of enzyme, alcohol, solvent and temperature were optimised during the present investigation. Butanol and hexanol were found to be suitable for formation of S and R esters, respectively. Hexane was the best solvent for esterification and the optimum temperature was found to be 30 degreesC.

Analgesics↗

PubMedDate not supplied

The cholecystokinin antagonist proglumide enhances the analgesic effect of dihydrocodeine.

AIM: To investigate the potential pro-analgesic effect of the non-specific CCK antagonist proglumide on the analgesia produced by dihydrocodeine. METHOD: A double-blind, placebo-controlled crossover study of 30 adult subjects. RESULTS: Mean pain scores fell from a baseline of 8.12-7.89 during the placebo phase (N.S.) and to 6.82 during the proglumide phase (P < 0.05). Side effects were minor. CONCLUSION: The CCK antagonist proglumide enhances the analgesic effect of dihydrocodeine.

Adult↗

PubMed1983

Proglumide: selective antagonism of excitatory effects of cholecystokinin in central nervous system.

Extracellular single-unit recording techniques were used to test the ability of proglumide to block cholecystokinin-induced excitation of rat midbrain dopaminergic neurons and dopamine-sensitive prefrontal cortex cells. Intravenous and iontophoretic proglumide administration consistently blocked cholecystokinin-induced excitations while having no effect on glutamic acid-induced increases in activity. This selective blockade of central cholecystokinin effects by proglumide suggests that this drug may be valuable for studying the possible role of cholecystokinin as a neurotransmitter or neuromodulator in the central nervous system.

Animals↗

PubMed1984

Pentagastrin induced motility pattern in the human upper gastrointestinal tract is reversed by proglumide.

The effects of pentagastrin and the putative gastrin antagonist proglumide on interdigestive motility of the upper small bowel were studied in a randomised double blind study in 10 healthy human volunteers. Intraluminal pressures were recorded manometrically in the duodenum and jejunum for five hours. Sixty minutes after starting a pentagastrin infusion (0.15 micrograms/kg/h) either placebo or proglumide was infused intravenously. Pentagastrin converted the normal interdigestive motility to irregular motor activity, while proglumide restored the periodic fasted pattern. We conclude that gastrin is a likely candidate involved in the conversion of the fasted to the fed motility pattern in the human upper gut.

Duodenum↗

PubMed1986

New proglumide-analogue CCK receptor antagonists: very potent and selective for peripheral tissues.

The present study evaluates the ability of two recently synthesized analogues of proglumide, both 4-benzamido-N,N-di-alkyl-glutaramic acid derivatives, to act as cholecystokinin receptor antagonists. Both new antagonists inhibited cholecystokinin-stimulated amylase release and, similarly, binding of 125I-cholecystokinin to isolated rat pancreatic acini. These effects displayed competitive kinetics; both antagonists showed no agonist activity and were specific in that only those secretagogues were inhibited that interact with the cholecystokinin receptor. Both antagonists also inhibited binding of 125I-cholecystokinin to mouse pancreatic membrane particles similarly to results with rat pancreatic acini. With the more potent of the two new antagonists, half-maximal inhibition of action and binding of cholecystokinin was observed with low concentrations of approximately 10(-7) M; compared with proglumide, the new antagonists were as much as 4,000 times more potent. Unlike proglumide, which inhibits binding of cholecystokinin to pancreas and brain tissue similarly, both antagonists inhibited binding of cholecystokinin to the pancreas at much lower concentrations compared with brain. The more potent of the inhibitors was 300 times more potent in inhibiting binding of cholecystokinin to pancreatic tissues compared with brain.

Amylases↗

PubMed1976

Double-blind comparison of the antirheumatic activity and gastric side-effects of indomethacin used alone or in combination with a gastro-protective agent, proglumide.

A double-blind placebo controlled trial was carried out in 32 hospitalized patients with various rheumatic disorders to assess the therapeutic effectiveness and gastric tolerance of indomethacin (150 mg/day) used alone or in combination with proglumide (900 mg/day). Patients were treated for periods ranging from 20 to 28 days. The therapeutic response to both treatments, as assessed by objective criteria and final overall evaluation, was not significantly different. There was, however, a marked difference in gastric disturbance between the two groups. Uropepsinogen levels increased significantly during treatment in patients receiving indomethacin plus placebo but decreased significantly after Day 10 in those receiving proglumide. Although stomach X-ray or faecal occult blood investigations showed litle change from normal in either group, no gastric side-effects were reported in the proglumide patients whereas only 2 of the 16 patients receiving indomethacin plus placebo were entirely free of such side-effects throughout the trial, and most had developed gastric symptoms by the 9th day of treatment.

Adult↗

PubMed1978

Double-blind clinical comparison between a gastrin-receptor antagonist, proglumide, and a histamine H2-blocker, cimetidine.

A double-blind trial was carried out in 30 patients with peptic ulcers to assess the effects of treatment with a gastrin-receptor antagonist, proglumide, compared with a histamine H2-blocker, cimetidine. Patients received either 1200 mg proglumide or 1200 mg cimetidine per day for 28 days. The results showed that both drugs significantly reduced clinical symptoms and gastric secretion. In patients treated with cimetidine there was a significant increase in blood gastrin levels and marked hypertrophy and hyperplasia of the antral mucosa was observed in almost all patients. No such changes were found in the patients treated with proglumide.

Adult↗

PubMed1990

Bombesin-induced pancreatic secretion and growth in rats: effect of proglumide, spantide and ranitidine.

The effect of proglumide (400 mg/kg), spantide (400 g/kg) and ranitidine (20 mg/kg) on pancreatic secretory and trophic response to bombesin (10 micrograms/kg) was studied in the rat. Drugs were administered alone or combined with bombesin three times daily for 5 days. Saline-treated rats were used as controls. At the end of treatment, animals were anaesthetized and pancreatic juice was collected for 1 h after caerulein stimulation (1 microgram/kg intraperitoneally). Afterwards, rats were sacrificed and the weight and composition of pancreatic tissue were determined. As compared with control (saline) values, the volume of pancreatic juice and the output of trypsin and amylase were increased by treatment with bombesin. Neither proglumide nor spantide affected basal and caerulein-stimulated pancreatic exocrine secretion. Ranitidine, although unable to modify protein and enzyme content of pancreatic secretion, significantly reduced the volume of pancreatic juice in both basal conditions and after caerulein stimulation. Bombesin increased pancreatic weight as well as the protein and enzymatic contents of the gland. Neither the weight of the pancreas nor its composition were significantly affected by CCK-antagonist proglumide, the putative bombesin antagonist spantide or the H2-receptor antagonist ranitidine. These results show that bombesin has a trophic effect on rat pancreas and concomitantly increases its secretory capacity. Both effects are likely to be mediated through a direct action of the peptide on the pancreatic gland.

Animals↗

PubMed1983

[Transmural gastric potential difference (PD) and intragastric diurnal pH profile with proglumide].

The presented double-blind cross-over-study evaluates the effect of proglumide on gastric potential difference (PD) and the PD-response to irritation of the gastric mucosal barrier by acetylsalicylic acid (ASA). Both, in an acute and a 6-day trial, no protective effect against the mucosal barrier breaker ASA was noticed. Furthermore, the 6-day administration of proglumide neither changed the 23-hour gastric pH-profiles nor the postprandial course of intragastric pH. The findings are shown in contrast to the action of cimetidine. The study shows, that proglumide neither reduces the aggressive factor acidity nor works protective at the gastric mucosal barrier.

Adult↗

PubMed1982

High-performance liquid chromatographic determination of proglumide in plasma.

A rapid and sensitive method for determining the anticholinergic agent, proglumide, in plasma by high-performance liquid chromatography is described. Samples were acidified with hydrochloric acid and extracted with chloroform. The dried extract was resolved in chloroform and chromatographed on an adsorption chromatographic column using a mobile phase of chloroform-methanol (24:1) on a high-performance liquid chromatograph equipped with a UV absorbance detector (240 nm). The detection limit for proglumide was 0.05 microgram/ml.

Chromatography, High Pressure Liquid↗

PubMed1984

The effects of proglumide on morphine induced motility changes.

Proglumide (0.02 mg/kg), a cholecystokinin antagonist, was administered to rats either together with or without morphine (0, 5, 15, or 45 mg/kg). Whereas proglumide in the absence of morphine showed a trend towards enhanced behavioral activation, it potentiated the hypokinesia induced by morphine. These results are consistent with the hypothesis that endogenous cholecystokinin tonically antagonizes opiate modulation of motility, irrespective of whether such modulation is produced by opiates and endogenous or exogenous origin.

Animals↗

PubMed1987

Proglumide peptides and CCK antagonistic action in hog duodenal circular muscle.

New proglumide peptides were synthesized and their inhibitory activity against the cholecystokinin (CCK)-induced relaxation was tested in duodenal circular muscles of hogs in order to locate the active moiety. Isotonic tension is reported as a percentage of the relaxation induced by CCK-4 (4.23 microM) or by Ca-free EGTA (2 mM). In R1-CONHCH(CH2CH2CO-R2)CON(CH2CH2CH3)2, P2-II(R1 = PhCH2O, R2 = Phe33-NH2), its D isomer and P3-I (R1 = Ph, R2 = Asp32-Phe33-NH2) had potent antagonistic activity (IC50 = 47.9 (32.4-72.4) microM, 25.1 (10.0-61.7) microM and 186 (141-240) microM, respectively). Benzotript, from another group of CCK antagonists had an IC50 of 52.5 (40.7-67.6) microM. P2-II (49 microM) or its D isomer (19.6 microM) antagonized non-competitively, and P3-I (168 microM) and benzotript (58.4 microM) antagonized competitively the CCK-4-induced relaxation. P3-I (84 or 168 microM) also antagonized competitively the CCK-8-induced relaxation. The amino acids of Tyr27, Trp30 and Phe33, separately, play important roles for agonist activity for relaxation. Tyr27 is the main relaxing group, Trp30 an antagonistic one and Phe33 is another relaxing one. In the proglumide skeleton, N,N-dipropylglutaramic acid acts like Trp30. Agonist, partial agonist and antagonist activities are exerted by these three groups and bulky substituents.

Animals↗