naloxone has been researched along with Stomach-Ulcer* in 36 studies
36 other study(ies) available for naloxone and Stomach-Ulcer
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Analagesic and Anti-Inflammatory Potentials of a Less Ulcerogenic Thiadiazinethione Derivative in Animal Models: Biochemical and Histochemical Correlates.
Gastric ulcer induced by NSAIDs is the major medical concern and researchers are utilizing several approaches to combat this medical issue. In the current study, we investigated the efficacy of thiadiazinethione derivative (2,2'(2-thioxo-1,3,5-thiadiazinane-3,5-diyl) diacetic acid, as new less ulcerogenic compound.. 2,2'(2-thioxo-1,3,5-thiadiazinane-3,5-diyl) diacetic acid was evaluated using standard animal models including hot plate, writhing test and formalin induced nociceptive models. Anti-inflammatory activity was assessed via carrageenan-induced paw oedema model. Involvement of opioidergic nociceptive mechanism was confirmed via naloxone administration in hot plat assay. The gastro-ulcerogenic potential of test and standard compounds were evaluated via NSAID-induced pyloric ligation model followed by standard histopathological and biochemical analysis.. In acetic acid-induced writhing test, our compound significantly reduced abdominal constrictions at the tested doses of 15 (. Our findings suggests that our test compound has desirable anti-nociceptive and anti-inflammatory potentials with less propensity to cause gastric ulcer. Topics: Analgesics; Animals; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Carrageenan; Edema; Formaldehyde; Naloxone; Stomach Ulcer; Tramadol; Ulcer | 2022 |
Gastroprotective and ulcer healing effects of hydroethanolic extract of leaves of Caryocar coriaceum: Mechanisms involved in the gastroprotective activity.
This work aimed to determine the chemical fingerprint of hydroethanolic extract of leaves of Caryocar coriaceum (HELCC) and the gastroprotective activity. The chemical fingerprint of HELCC was analyzed by HPLC-DAD, to quantify total phenols and flavonoids were carried out by Folin-Ciocalteu reagent and aluminum chloride assay, while in vitro antioxidant activity was evaluated by the DPPH method. The methods used to determine pharmacological activity were: gastroprotective screening test in classical models of induced acute and chronic gastric lesions and physical barrier test. Further assays were performed to demonstrate the involvement of NO, prostaglandins, ATP-dependent potassium channels, TRPV, noradrenergic α2 receptors, histamines, and opioids. The DPPH method demonstrated the antioxidant activity of the extract, in vitro, explained by the presence of polyphenols and flavonoids. Oral administration of the extract, previously dissolved in deionized water, at a dose of 100 mg/kg decreased the lesions induced by indomethacin, acidified ethanol, ethanol and acetic acid by 75.0, 72.8, 69.4 and 86.2% respectively. It was demonstrated that opioid receptors, α Topics: Animals; Antioxidants; Capsaicin; Chromatography, High Pressure Liquid; Chronic Disease; Disease Models, Animal; Ericales; Ethanol; Female; Flavonoids; Gastrointestinal Motility; Glyburide; Histamine; Indomethacin; Male; Mice; Mucus; Naloxone; NG-Nitroarginine Methyl Ester; Phenols; Phytotherapy; Plant Extracts; Plant Leaves; Protective Agents; Stomach Ulcer; Water; Yohimbine | 2017 |
Antinociceptive action of 4-methyl-5-trifluoromethyl-5-hydroxy-4, 5-dihydro-1H-pyrazole methyl ester in models of inflammatory pain in mice.
The aim of the present study was to evaluate the antinociceptive effect of the novel pyrazoline methyl ester: 4-methyl-5-trifluoromethyl-5-hydroxy-4,5-dihydro-1H-pyrazole methyl ester (MPF4).. The effect of MPF4 was assessed in two models of pain: arthritic pain caused by Complete Freund's Adjuvant (CFA) and postoperative pain caused by surgical incision in mice.. MPF4 given intraperitoneally (1.0 mmol/kg, i.p.) produced marked antinociception in inflammatory allodynia caused by CFA. The antinociceptive effect produced by MPF4 was reversed with the pre-treatment of animals with naloxone or naltrindole. Oral administration of MPF4 (1.0 mmol/kg, p.o), dipyrone (1.0 mmol/kg, p.o.) and morphine (0.026 mmol/kg, p.o.) also produced an anti-allodynic effect. However, none of the compounds evaluated reversed the paw edema produced by CFA. Moreover, MPF4, dipyrone and morphine also produced an anti-allodynic effect in the surgical incisional pain model. The maximal inhibitions obtained with preemptive drug treatment were 66+/-7%, 73+/-9% and 88+/-8% for MPF4 (1.0 mmol/kg, p.o.), dipyrone (1.0 mmol/kg, p.o.) and morphine (0.026 mmol/kg, p.o.), respectively. The maximal inhibitions obtained with curative drug treatment were 53+/-9%, 83+/-7% and 84+/-7%, for MPF4, dipyrone and morphine, respectively. Unlike indomethacin, MPF4 did not induce gastric lesions at the dose that caused the highest antinociception (1.0 mmol/kg, p.o). The anti-allodynic action of MPF4, dipyrone and morphine was not associated with impairment of motor activity.. The results of the present study suggest that MPF4 represents a potential target for the development of new drugs to treat persistent inflammatory pain. Topics: Analgesics; Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Experimental; Dipyrone; Freund's Adjuvant; Indomethacin; Inflammation; Male; Mice; Morphine; Motor Activity; Naloxone; Naltrexone; Narcotic Antagonists; Pain; Pain, Postoperative; Postural Balance; Pyrazoles; Stomach Ulcer | 2008 |
[Analysis of central mechanisms involved in gastric mucosal integrity].
Beta-endorphin, deltorphin II, [D-Ala2, Phe4, Gly5-ol-enkephalin (DAGO) as well as endomorphin-1 and endomorphin-2 injected intracerebroventricularly (i.c.v.) induced gastroprotective action. It has been raised that endogenous opioids may have a central role in maintaining gastric mucosal integrity. Therefore we aimed to study the role of endogenous opioid system in the gastroprotective action induced by activation of alpha 2-adrenoceptors, nociceptin- and cannabinoid-receptors. Our results suggest that the non-selective opioid receptor antagonist naloxone (27 nmol i.c.v.) and the delta-opioid receptor antagonist naltrindole (5 nmol i.c.v.) abolished the mucosal protective effect of alpha 2-adrenoceptor agonists clonidine (470 pmol i.c.v.) and rilmenidine (45 pmol i.c.v.), nociceptin (1 nmol i.c.v.) and the cannabinoid receptor agonist anandamide (110 nmol i.c.v.). Based on our findings it can be raised that opioid system besides its well known regulatory functions might be involved in maintenance of gastric mucosal integrity. Topics: Animals; Arachidonic Acids; beta-Endorphin; Clonidine; Endocannabinoids; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Ethanol; Excitatory Amino Acids; Gastric Mucosa; Injections, Intraventricular; Male; Naloxone; Naltrexone; Narcotic Antagonists; Neurotransmitter Agents; Nociceptin; Oligopeptides; Opioid Peptides; Oxazoles; Polyunsaturated Alkamides; Rats; Rats, Wistar; Receptors, Opioid; Rilmenidine; Stomach Ulcer | 2008 |
Characterisation of alpha2-adrenoceptor subtypes involved in gastric emptying, gastric motility and gastric mucosal defence.
The effect of clonidine on ethanol-induced gastric mucosal damage, gastric emptying and gastric motility was compared. The clonidine-induced gastroprotective effect (0.03-0.09 micromol/kg, s.c.) was antagonised by yohimbine (5 micromol/kg, s.c.), prazosin (0.23 micromol/kg; alpha2B-adrenoceptor antagonist) and naloxone (1.3 micromol/kg, s.c.). Clonidine also inhibited the gastric emptying of liquid meal (0.75-3.75 micromol/kg, s.c.) and gastric motor activity (0.75 micromol/kg, i.v.) stimulated by 2-deoxy-D-glucose (300 mg/kg, i.v.). Inhibition of gastric emptying and motility was reversed by yohimbine (5 and 10 micromol/kg, s.c., respectively), but not by prazosin (0.23 micromol/kg, s.c.) or naloxone (1.3 micromol/kg, s.c.). Oxymetazoline-an alpha2A-adrenoceptor agonist-inhibited both gastric emptying (0.67-6.8 micromol/kg, s.c.) and motility (0.185-3.4 micromol/kg, i.v.), whereas it failed to affect gastric mucosal lesions. The results indicate that in contrast to the gastroprotective effect, which is mediated by alpha2B-adrenoceptor subtype, alpha2A-adrenoceptor subtype may be responsible for inhibition of gastric emptying and motility. However, the site of action (central, peripheral, both) remains to be established. Topics: Adrenergic alpha-Agonists; Adrenergic alpha-Antagonists; Animals; Clonidine; Disease Models, Animal; Dose-Response Relationship, Drug; Ethanol; Gastric Emptying; Gastric Mucosa; Gastrointestinal Motility; Male; Muscle Contraction; Muscle, Smooth; Naloxone; Narcotic Antagonists; Oxymetazoline; Prazosin; Rats; Rats, Wistar; Receptors, Adrenergic, alpha-2; Stomach Ulcer; Yohimbine | 2005 |
Morphine as a drug for stress ulcer prevention and healing in the stomach.
Morphine pretreatment protects against stress-induced gastric ulceration, however, the exact mechanism is still undefined. Interestingly, the effect of morphine on ulcer healing has not been investigated. In this report, we would like to study these effects in a defined stress ulcer model and to delineate a new implication for morphine to promote stress ulcer healing in rats. Our study showed that cold-restraint stress for 3 h induced hemorrhagic lesions and increased myeloperoxidase activity in the gastric mucosa. Stress also reduced the dimension of layer of periodic acid-Schiff reagent-stained cells in the gastric mucosa by about 50%. Morphine pretreatment (2 or 8 mg/kg, given intraperitoneally) at the time of stress dose-dependently reversed stress-induced gastric ulceration, increase of myeloperoxidase activity and reduction of thickness of mucus-stained cells in the gastric mucosa. Morphine treatment after stress (given at the end of a 3-h stress and also at 3 h thereafter) increased ulcer healing by reducing the ulcer size measured 24 h later. Such action was blocked by naloxone (8 mg/kg) given intraperitoneally 15 min before morphine treatment. Morphine also increased the number of cell proliferation and dimension of layer of cells stained for mucus but not the number of microvessels in the gastric mucosa. Moreover, the number of apoptotic cells was less evidenced in the morphine-treated rats. This study reports for the first time that morphine not only prevents stress ulceration but also promotes healing of stress ulcer through a defined mechanism. Topics: Analgesics, Opioid; Animals; Apoptosis; Blood Vessels; Cell Division; Cold Temperature; Gastric Mucosa; Male; Morphine; Naloxone; Rats; Rats, Sprague-Dawley; Stomach; Stomach Ulcer; Stress, Physiological; Time Factors; Wound Healing | 2003 |
Naloxone is protective against indomethacin-induced gastric damage in cholestatic rats.
We compared indomethacin-induced gastric damage in three groups of rats-bile duct-ligated, sham-operated, and unoperated-and evaluated the role of the opioid system by blocking the effects of endogenous opioids with naloxone. Indomethacin was administered orally in a dose-dependent manner at 10, 30, and 45 mg/ kg. Naloxone was administered intraperitoneally in several doses of 0.5 and 1 mg/kg, starting 30 min before indomethacin (10mg/kg) administration and continued every 30 min. The animals were killed 4h after indomethacin administration. Indomethacin induced more severe gastric damage in bile duct-ligated rats than in sham and unoperated animals, and administration of naloxone (1 mg/kg) every 30 min inhibited the potentiation of indomethacin-induced gastric damage in bile duct-ligated rats, but not in the control groups (sham-operated and unoperated rats). Plasma indomethacin level was also measured, by fluorometry, but showed no significant difference between the groups. Endogenous opioids have been reported to accumulate in plasma of cholestatic animals, and, considering the results of this study, we suggest the opioid system plays an important pathophysiologic role in the pathogenesis of peptic ulcers in cholestatic subjects. Topics: Animals; Cholestasis; Dose-Response Relationship, Drug; Gastric Mucosa; Indomethacin; Male; Naloxone; Narcotic Antagonists; Rats; Stomach Ulcer | 1999 |
The effects of captopril and naloxone on restraint-cold-stress- and ethanol-induced gastric lesions in rats.
1. This study was undertaken to investigate the effect of captopril (1 microgram/kg or 1 mg/kg, i.p.) on the actions of naloxone (5 mg/kg, i.p. in gastric ulceration induced by ethanol and restraint-cold-stress. 2. Neither naloxone (5 mg/kg, i.p.) nor captopril (1 mg/kg, i.p.) alone induced any change in the indices of the ulcer in either group. 3. Captopril at a lower dose (1 microgram/kg, i.p.), when combined with naloxone (5 mg/kg, i.p.), significantly reduced cumulative ulcer length only in the ethanol-treated group (from 54.9 +/- 7.2 mm to 22.5 +/- 6.2 mm). 4. However, a high dose of captopril (1 mg/kg) plus naloxone pretreatment caused a significant reduction in both ethanol (from 54.9 +/- 7.2 mm to 24.9 +/- 6.5 mm) and restraint-cold-stress (from 19.0 +/- 3.0 mm to 5.3 +/- 1.0 mm)-induced ulcer formation. 5. Acetylsalycilic acid, when used together with captopril, increased the ulcer formation induced by stress. 6. Naloxone, by increasing the release of prostaglandins, has been shown to prevent ulcer formation induced by several noxious stimuli. 7. Therefore, the effect of the combination might be due to the synergistic interaction of both drugs on prostaglandin synthesis. Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Captopril; Drug Synergism; Drug Therapy, Combination; Ethanol; Female; Male; Naloxone; Prostaglandins; Rats; Restraint, Physical; Stomach Ulcer; Stress, Physiological | 1998 |
Effects of majonoside-R2 on pentobarbital sleep and gastric lesion in psychologically stressed mice.
The effects of Vietnamese ginseng (VG) and its major constituent majonoside-R2 on pentobarbital-induced sleep and gastric lesion in psychologically stressed mice were examined. Psychological stress exposure for 30 min significantly decreased the duration of pentobarbital (50 mg/kg, IP)-induced sleep in mice. VG extract (50 mg/kg, PO), VG saponin (25 mg/kg, PO), and majonoside-R2 (3.1-12.5 mg/kg, PO and IP) had no effect on pentobarbital sleep in unstressed control mice, but these drugs significantly recovered pentobarbital sleep decreased by psychological stress to the level of unstressed control animals. On the other hand, Panax ginseng (PG) extract (50-100 mg/kg, PO) failed to affect pentobarbital sleep in psychologically stressed mice. The effect of majonoside-R2 on psychological stress-induced decrease in the hypnotic activity of pentobarbital was significantly blocked by flumazenil (1 mg/kg, IV), a selective benzodiazepine antagonist. Diazepam (0.1 mg/kg, IP) significantly prolonged pentobarbital sleep in unstressed and psychologically stressed groups, and the effect of diazepam was significantly attenuated by the same dose of flumazenil. Naloxone (0.5-5 mg/kg, IP), an opioid antagonist, had no effect on pentobarbital sleep in unstressed or psychologically stressed animals. Psychological stress exposure for 16 h caused gastric lesion in mice. VG extract (25-50 mg/kg, PO) and majonoside-R2 (6.2-12.5 mg/kg, PO), as well as diazepam and naloxone, produced the protective action on gastric lesion in psychologically stressed mice. These results suggest that VG and its major constituent majonoside-R2 have the protective effects on the psychological stress-induced pathophysiological changes and that benzodiazepine receptors are partly implicated in the effects of majonoside-R2. Topics: Animals; Diazepam; Ginsenosides; Hypnotics and Sedatives; Male; Mice; Mice, Inbred Strains; Naloxone; Narcotic Antagonists; Panax; Pentobarbital; Plant Extracts; Plants, Medicinal; Saponins; Sleep; Stomach Ulcer; Stress, Psychological; Time Factors | 1996 |
Prevention of stress-induced gastric ulcers by mu- and delta-opioid agonists in the rat.
The effects of intraperitoneal and intracerebroventricular administration of mu- and delta- selective opioid receptor agonists (DAGO and DPDPE, respectively) on gastric lesions, were investigated in cold-restraint-stressed rats. DAGO and DPDPE, peripherally and centrally administered, induced a significant gastric protection. Naloxone prevented the effects of both opioids whereas naltrindole prevented the gastric protection induced by DPDPE but not that by DAGO. The results suggest that mu- and delta-opioid agonists prevent gastric damage induced by stress through an involvement of both central and peripheral mu- and delta-opioid receptor subtypes. Topics: Animals; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Enkephalin, D-Penicillamine (2,5)-; Enkephalins; Male; Naloxone; Rats; Rats, Sprague-Dawley; Receptors, Opioid, delta; Receptors, Opioid, mu; Restraint, Physical; Stomach Ulcer; Stress, Physiological | 1993 |
Naloxone-sensitive potentiation at granule cell synapses in the ventral dentate gyrus and stress ulcers.
Continuous perfusion of the granule cells in the ventral dentate gyrus with naloxone blocked the long-term potentiation (LTP) induced by high-frequency electrical stimulation of the posterolateral amygdala in freely-moving rats. This treatment also aggravated the stomach ulceration produced by cold restraint. LTP, on the other hand, attenuated the gastric stress pathology. It was suggested that a naloxone-sensitive granule cell gate modulates the impact of environmental stressors. Topics: Animals; Arousal; Enkephalin, Methionine; Hippocampus; Male; Naloxone; Neurons; Rats; Rats, Inbred Strains; Receptors, Opioid; Stomach Ulcer; Stress, Psychological; Synapses; Synaptic Transmission | 1992 |
Naloxone and restraint stress: effects on gastric mucosal injury and gastric function.
Contradictory findings have been reported from previous investigations of the effects of opiate receptor blockade on stress-related gastric injury. We performed two studies of the effects of naloxone on gastric mucosal injury and gastric function in cold restraint stress. In the first, naloxone had a linear, dose-dependent effect, reducing mucosal injury both parenterally and enterally. Gastric acidity was not related to the dose of naloxone, or to the amount or extent of mucosal injury. Gastric residual volume, by contrast, was related to both naloxone dose and gastric mucosal injury. In the second study we investigated the effect of gastric distention by enteral vehicle in the restraint model, and the interaction of the vehicle with the effects of naloxone. Periodic distention of the stomach with enteral vehicle did not alter the drug's effects on mucosal injury or on gastric residual volume. Because cold restraint stress produces harmful gastric contractions, naloxone is likely to be protective by altering gastric motility. Topics: Animals; Cold Temperature; Gastric Mucosa; Humans; Hydrogen-Ion Concentration; Male; Naloxone; Random Allocation; Rats; Rats, Inbred Strains; Stomach; Stomach Ulcer; Stress, Psychological | 1992 |
Antisecretory and anti-ulcer effects of morphine in rats after gastric mucosal aggression.
The effects of morphine on gastric secretion, barrier mucus and mucosal lesions were studied in pylorus-ligated rats treated with the ulcerogenic agents, indomethacin, aspirin or taurocholic acid. All three ulcerogenic agents induced significant mucosal lesions. Morphine decreased gastric acid secretion and suppressed the aspirin- and taurocholic acid-induced, but not the indomethacin-induced mucosal lesions. These results suggest that the ulcerogenic mechanisms of indomethacin and the other agents are not identical. Moreover the antiulcer effect of morphine appears to be mediated by an increased barrier mucus level: the amount of Alcian blue bound to the mucosa, an indirect estimate of the adherent mucus layer, was increased by morphine and correlated with its protective effect. All morphine effects were reversed by naloxone. Topics: Animals; Aspirin; Depression, Chemical; Gastric Acid; Gastric Mucosa; Indomethacin; Male; Morphine; Mucus; Naloxone; Rats; Rats, Inbred Strains; Stomach Ulcer; Taurocholic Acid | 1991 |
Aggravating action of clonidine on ethanol-induced gastric lesions: probable mechanism of action.
Large doses of the imidazoline alpha 2 adrenoreceptor agonist clonidine aggravate ethanol-induced gastric lesions. The alpha 2 adrenoceptor antagonist phentolamine, the opioid antagonist naloxone and the H2 antagonist cimetidine do not prevent this action of clonidine suggesting that it is not mediated by alpha 2, opioid or H2 receptors. Further, like clonidine, high doses of phentolamine and cimetidine aggravate gastric lesions per se, suggesting that all three may be acting at a common 'receptor' site, possibly the imidazoline-preferring receptor (IPR). Topics: Animals; Cimetidine; Clonidine; Drug Synergism; Ethanol; Male; Naloxone; Phentolamine; Rats; Rats, Inbred Strains; Receptors, Histamine H2; Receptors, Opioid; Stomach Ulcer | 1990 |
The effect of naloxone in the prevention of experimental stress ulcers in rats.
In this study, the effect of naloxone in the prevention of experimental stress ulcers was investigated. A prophylactic effect of naloxone on stress ulcer formation was not observed. On the contrary, naloxone increased the gastric lesion score. Naloxone did neither decrease gastric acidity in stress nor in non-stress conditions. Under non-stress conditions naloxone did not change gastric mucosal barrier by reducing Na+ and K+ ion concentrations of the gastric secretion. Under stress conditions the barrier could not be maintained. Naloxone decreased gastric mucus production under stress. Topics: Animals; Arousal; Gastric Acid; Gastric Mucosa; Naloxone; Rats; Rats, Inbred Strains; Receptors, Opioid; Stomach Ulcer; Stress, Psychological | 1990 |
Naloxone-insensitive modulation of gastric acid output by [D-Met2,Pro5]enkephalinamide in rats.
Studies from our laboratory have previously shown that two opioid agonists (morphine and [D-Met2,Pro5]enkephalinamide) aggravate, whereas naloxone inhibits cold-restraint stress-induced ulceration in rats. In the present study the effects of these substances were examined using the Shay-model. Contrary to expectations, both naloxone and the opioid agonists decreased gastric acid output. Naloxone in combination with either opioid agonist failed to reverse their inhibitory action. Thus the secretory activity of the stomach may be modulated by opioids in both naloxone-reversible and irreversible ways. Topics: Animals; Enkephalin, Methionine; Gastric Acid; Male; Morphine; Naloxone; Pylorus; Rats; Rats, Inbred Strains; Stomach Ulcer | 1990 |
The effect of different opiates on acidified ethanol-induced gastric lesions in rats.
Topics: Animals; Benzomorphans; Enkephalin, Methionine; Ethanol; Morphine; Naloxone; Narcotics; Rats; Stomach Ulcer | 1990 |
Nociceptive sensitivity/behavioral reactivity regulation in rats during aversive states of different nature: its mediation by opioid peptides.
To study the regulation of nociceptive sensitivity/behavioral reactivity in animals during aversive states of different nature, the changes of vocalization thresholds and tail-withdrawal latencies were investigated in rats in free behavior, during restraint stress, after acute trauma to an extremity and under intraperitoneal acetic acid administration. To understand opioid peptide involvement in mediation of the changes obtained, this analysis was also done during opiate receptor blockade by naloxone. The data on the modification of vocalization and movement reactivity as well as on the changes of suprarenal weight and gastric ulceration, produced in normal and naloxone-treated rats by innoxious stressogenic, noxious somatic and visceral stimulation are discussed in relation with: 1. the peculiarities of sensitivity and responsivity of animals to external stimuli in aversive environment; 2. the role of these changes in maintenance of an animal's adaptive activity produced by environmental threat and their mediation by endogenous opioids; 3. the functional significance of the activation of endogenous opioidergic neurotransmission in organization, realization and modification of an animal's adaptive activity, directed on behavioral escape from aversive environment as well as on satisfaction of actual biological and zoosocial needs, in regulation of precise conformity among homeostasis, behavior and variable environment. Topics: Acetates; Acetic Acid; Animals; Avoidance Learning; Behavior, Animal; Body Weight; Endorphins; Female; Male; Naloxone; Nociceptors; Noise; Pain; Rats; Restraint, Physical; Stomach Ulcer; Stress, Psychological; Vocalization, Animal | 1989 |
Naloxone exerts a dose-dependent gastric cytoprotective effect.
Previous work has shown that naloxone inhibits the ulcerogenic effects of indomethacin and stress, although the site, mechanism or dose are unknown. We investigated whether naloxone possessed gastric cytoprotective properties, generating a dose-response curve existed for both intragastric (IG) and intravenous (IV) administration. One hundred and two rats were subjected to a four hour period of restraint, with the last two hours at 4 degrees C. Naloxone was given hourly during restraint at doses of 0 (Control), 1, 5, 10, 20 mg/kg. After sacrifice, the residual gastric volume, and pH were measured and the number of mucosal lesions scored. The cytoprotection offered by naloxone was different from control (p = 0.0001), with the intravenous route having a greater effect (p = 0.038). While this protective effect did not correlate with changes in gastric acidity, it correlated with the dose of naloxone. Topics: Animals; Dose-Response Relationship, Drug; Gastric Mucosa; Hydrogen-Ion Concentration; Male; Naloxone; Rats; Rats, Inbred Strains; Stomach Ulcer; Stress, Physiological | 1989 |
Pemedolac: a novel and long-acting non-narcotic analgesic.
Pemedolac [cis-1-ethyl-1,3,4,9-tetrahydro-4-(phenylmethyl)-pyrano [3,4-b]indole-1-acetic acid; AY-30,715] exhibited potent analgesic effects against chemically induced pain in rats and mice and against inflammatory pain in rats. In each of the animal models used the analgesic potency of pemedolac was defined by an ED50 of 2.0 mg/kg p.o. or less. Significant analgesic activity was detected in rats at 16 hr after administration of 1 mg/kg p.o. (paw pressure test) and at 10 hr after administration of 10 mg/kg p.o. to mice (p-phenylbenzoquinone writhing). Inasmuch as pemedolac was inactive in the hot plate and tail-flick tests; and its analgesic activity was not antagonized by naloxone (1 mg/kg s.c.), and tolerance did not develop upon multiple administration; this drug does not exert its analgesic effects through an opiate mechanism. Pemedolac differed from standard nonsteroidal anti-inflammatory drugs (NSAIDs) in that the doses which produced analgesia were much lower than those required for either anti-inflammatory or gastric irritant effects. In acute anti-inflammatory tests, pemedolac exhibited only weak activity as evidenced by an ED50 approximately 100 mg/kg p.o. in the carrageenan paw edema procedure. This demonstrates for pemedolac a separation of at least 50-fold between the acute analgesic and anti-inflammatory activities, which was greater than that observed with reference NSAIDs. The compound also had a low ulcerogenic liability with an acute UD50 = 107 mg/kg p.o. and a subacute UD50 estimated to be 140 mg/kg/day p.o. In contrast, the reference NSAIDS (piroxicam, indomethacin, naproxen and ibuprofen) exhibited similar dose-response relationships for the analgesic, anti-inflammatory and gastric irritant effects.(ABSTRACT TRUNCATED AT 250 WORDS) Topics: Analgesics; Animals; Anti-Inflammatory Agents, Non-Steroidal; Drug Tolerance; Indoleacetic Acids; Male; Mice; Morphine; Naloxone; Rats; Rats, Inbred Strains; Stomach Ulcer; Substance-Related Disorders | 1989 |
Pharmacokinetics of naloxone: an insight into the locus of effect on stress-ulceration.
The purpose of this study was to determine if the beneficial effect of naloxone on formation of acute gastric mucosal lesions was brought about via central or peripheral mechanisms by measuring blood concentrations of naloxone in rats during a 4-hr period of restraint stress. The study involved administration of naloxone to rats at doses of 5, 20 and 40 mg.kg-1.hr by either the intravenous or enteral routes. Blood samples were collected throughout the period of restraint and gastric stress-lesions were counted at the end of the experiments. Both routes of administration were equally effective in preventing stress-ulceration, with only rats receiving drug intravenously showing the presence of naloxone in blood samples. Inverse linear relationships existed between mean trough blood concentrations and lesions (P = .0003), as well as a linear correlation between area under the time-concentration curve and mean trough concentrations (P = .0001). Although our results show tight correlation between blood levels and effect on lesions in the group given drug intravenously, the effect must be on peripheral rather than central opiate receptors as no detectable blood levels were found when naloxone was given enterally. Topics: Animals; Gastric Mucosa; Hydrogen-Ion Concentration; Male; Naloxone; Rats; Rats, Inbred Strains; Stomach Ulcer; Stress, Physiological | 1989 |
Opiate mechanisms in the central amygdala and gastric stress pathology in rats.
Bilateral microinjections of the opiate antagonist naloxone (0.1, 1.0 and 10.0 micrograms) into the central nucleus of the amygdala (CEA) produced a significant potentiation of cold restraint-induced gastric pathology in rats. The opiate agonist, beta-endorphin (0.1, 1.0 and 10.0 micrograms), on the other hand, inhibited stress ulcer formation in a dose-related manner. Stress ulcer-attenuating effects were also seen with intra-CEA injections of the enkephalin analogs [D-Ala2,D-Leu5]enkephalin (10.0 micrograms) and [D-Ala2]Met-enkephalinamide (10.0 micrograms). Pretreatment of rats with naloxone (1.0 microgram) completely antagonized and even reversed the gastric cytoprotective effects of beta-endorphin (1.0 and 10.0 micrograms). The results indicate that the CEA is important in the gastric cytomodulatory effects of endogenous opiates during stressful experiences. Topics: Amygdala; Animals; Endorphins; Enkephalin, Leucine; Enkephalin, Leucine-2-Alanine; Enkephalin, Methionine; Male; Microinjections; Naloxone; Rats; Rats, Inbred Strains; Receptors, Opioid; Restraint, Physical; Stomach Ulcer; Stress, Physiological | 1988 |
Effect of [D-Met2,Pro5]enkephalinamide on gastric ulceration and transmucosal potential difference.
The effects of [D-Met2,Pro5]enkephalinamide, morphine and naloxone have been examined in two different models of experimentally elicited gastric mucosal lesions. One of them was the classic cold-restraint stress-induced ulceration. The other was a less frequently applied procedure, involving the measurement of decreases in the transmucosal potential difference, which is also a sensitive indicator of mucosal damage. The opioid agonists studied, [D-Met2,Pro5]enkephalinamide and morphine, aggravated, whereas naloxone, the pure opiate antagonist, mitigated the lesions in both models. The protective action of naloxone points to an eventual role of endogenous opioids in the generation of these types of mucosal lesions. Morphine is selective ligand of mu-opiate receptors. The enkephalin analogue, however, binds to both mu- and delta-receptors. Therefore, the potent pro-ulcerogenic action of the enkephalin analogue indicates that both the mu- and delta-receptors were involved in these models of experimental gastric lesions. The clarification of the eventual role of kappa-receptors requires further experimental work with a selective ligand of this subtype of opiate receptors. Topics: Analgesics; Animals; Cold Temperature; Enkephalin, Methionine; Evoked Potentials; Gastric Mucosa; Male; Morphine; Naloxone; Rats; Rats, Inbred Strains; Restraint, Physical; Stomach Ulcer; Stress, Psychological | 1988 |
Pharmacological evidence of morphine-induced inhibition of gastric mucus synthesis in rats.
The effects of morphine, administered at graded doses by either intracerebroventricular (i.c.v.) or intraperitoneal (i.p.) routes, have been investigated on acid and pepsin outputs, secretory volume, ulcer score, free and bound gastric mucus, in pylorus-ligated rats. Morphine i.c.v. induced a dose-dependent inhibition of secretory volume, acid and pepsin outputs and ulcer score, without modification of either free or bound mucoproteins. Naloxone i.c.v. had no effect per se, but prevented the inhibitory effects of i.c.v. morphine. Morphine i.p. produced a dose-dependent inhibition of gastric secretory volume, acid and pepsin outputs, as well as both free and wall-bound mucoproteins. By contrast, the effect of i.p. morphine on ulcer score was not dose-dependent: the dose of 5 mg/kg induced significant exacerbation of gastric lesions. Naloxone at 0.8 mg/kg i.p. had no effect per se, whereas at the dose of 4 mg/kg it significantly increased bound gastric mucus. The dose of 0.8 mg/kg antagonized the effects of morphine on gastric secretory volume, acidity, pepsin and ulcer score, but not on gastric mucus. These results indicate that morphine affects gastric acidity through central and peripheral opiate receptors, whereas gastric mucus synthesis appears to be regulated through peripheral opioid pathways. Topics: Animals; Dose-Response Relationship, Drug; Gastric Acid; Gastric Mucosa; Male; Morphine; Mucoproteins; Mucus; Naloxone; Pepsin A; Rats; Rats, Inbred Strains; Stomach Ulcer | 1987 |
Effects of morphine on gastric ulceration, barrier mucus and acid secretion in pylorus-ligated rats.
The effects of intraperitoneal (IP) or intracerebroventricular (ICV) administration of morphine on acid and pepsin secretion, gastric ulceration and gastric bound mucoproteins were investigated in pylorus-ligated rats. Morphine, administered IP, produced a dose-dependent inhibition of the gastric secretion volume, acidity, pepsin output and bound mucoproteins. By contrast, the effect of morphine on gastric ulcers was not dose-dependent: a significant increase in gastric lesions was obtained with morphine 5 mg/kg IP. Naloxone IP prevented the effects of morphine on gastric secretory volume, acidity and pepsin output, but not on gastric mucus and ulcer score. ICV administration of morphine induced a dose-dependent inhibition of secretory volume, acidity and ulcer score, whereas no modification of gastric mucus was observed. Naloxone ICV prevented the effects of ICV morphine. Overall results suggest that morphine inhibits gastric secretion through both central and peripheral opioid receptors, whereas the inhibitory effect of morphine on bound mucus appears to be exerted on mucus synthesis through peripheral opioid receptors. This inhibitory effect on barrier mucus accounts at least in part for the gastric ulcerogenic action of morphine. Topics: Animals; Dose-Response Relationship, Drug; Gastric Acid; Gastric Mucosa; Injections, Intraperitoneal; Injections, Intraventricular; Ligation; Male; Morphine; Naloxone; Pylorus; Rats; Rats, Inbred Strains; Stomach Ulcer | 1987 |
Role of opioid receptors in stress induced gastric ulceration in rats.
Topics: Animals; Female; Loperamide; Male; Morphine; Naloxone; Rats; Receptors, Opioid; Stomach Ulcer; Stress, Physiological | 1986 |
Impaired contractile motility of the gallbladder after gastrectomy.
Contractile motility of the gallbladder was compared using a real-time ultrasonography in 13 patients with gastric ulcer and 31 patients with gastric cancer who had undergone either subtotal or total gastrectomy within 1 month previously. Contractile motility of the gallbladder after oral administration of dried egg yolk (Daiyan, Maruishi, Osaka), which was slightly but not significantly reduced in patients with gastric ulcer, was remarkedly impaired in patients with gastric cancer who had either subtotal or total gastrectomy including radical lymph node dissection. Especially, maximum contractile rate after Daiyan in Billroth II patients was significantly reduced than that of Billroth I patients. Intramuscular injection of naloxone (0.4 mg), which had no effects on contractions after Daiyan in healthy subjects, significantly improved the hypomotility in response to Daiyan in these gastric cancer patients. It was suggested, therefore, that the possible roles of various anatomical and mechanical changes resulting from gastrectomy including vagotomy and sympathectomy, and in particular exclusion of duodenum from digestive circuits and relative or absolute excess of endogenous opioids, were involved in the control of the gallbladder motility within 1 month after gastrectomy including lymphadenectomy. Topics: Colectomy; Egg Yolk; Gallbladder; Gastrectomy; Humans; Lymph Node Excision; Male; Middle Aged; Naloxone; Stomach Neoplasms; Stomach Ulcer; Sympathectomy; Ultrasonography; Vagotomy | 1986 |
Effects of morphine and naloxone on stress ulcer formation and gastric acid secretion.
The effect of both acute and chronic morphine and naloxone on restraint-stress gastric ulcer formation and on basal gastric acid secretion were examined in the conscious rat. Acute morphine administration produced a dose-related decrease in stress ulceration and basal gastric acid secretion. Acute naloxone treatment resulted in a dose-related increase in stress ulcer formation and markedly augmented gastric acid secretion. Naloxone (4.0 mg/kg) antagonized the ulcer-reducing effects at all doses of morphine tested (4.0-32.0 mg/kg). Morphine-dependent rats, restrained during spontaneous or naloxone-precipitated withdrawal, exhibited the most severe ulceration. However, only those subjected to naloxone-precipitated withdrawal produced a significant increase in gastric acid output. Chronic treatment with naloxone or with chronic naloxone followed by morphine (16.0 mg/kg) resulted in augmented stress ulcer formation relative to all acutely treated groups. Both chronic naloxone-treated groups exhibited markedly enhanced gastric secretion. These data suggest that central and/or peripheral opiate receptors can modulate both basal and stress-perturbed gastric function. Topics: Animals; Gastric Acid; Male; Morphine; Naloxone; Rats; Rats, Inbred Strains; Restraint, Physical; Stomach Ulcer; Stress, Psychological; Time Factors | 1986 |
Gastric mucosal damage induced by endotoxin shock and its prevention by naloxone and anti-ulcer drugs in rats.
Administration of endotoxin (20 mg/kg i.p.) produced a moderate degree of gastric mucosal damage in rats. The lesions remained confined to the glandular mucosa and consisted of small punctiform lesions, erosions and petechial hemorrhage. The characteristic feature of these lesions was a typical submucosal ecchymosis in the glandular stomach observed in about 30% of the animals. Pretreatment with ranitidine, pirenzepine, proglumide, sucralfate and naloxone produced varying degrees of protection. The ulcerogenic effect of endotoxin shock is apparently mediated through the release of endorphins. Topics: Animals; Anti-Ulcer Agents; Endotoxins; Female; Gastric Mucosa; Male; Naloxone; Rats; Rats, Inbred Strains; Shock, Septic; Stomach Ulcer | 1986 |
Analysis of the analgesic and anti-inflammatory effects of rimazolium, a pyrido-pyrimidine derivative, compared with that of prostaglandin synthesis inhibitors and morphine.
The analgesic, anti-inflammatory and gastrointestinal effects of rimazolium, morphine and prostaglandin synthesis inhibitors were compared in a battery of tests. Rimazolium, morphine and indomethacin all inhibited carrageenin-induced inflammation; however, the onset of action was different. The first (histamine-serotonin) phase was inhibited by rimazolium, the second (kinin) phase by morphine and the third (prostaglandin) by indomethacin. The chemoluminescence of leucocytes was inhibited by morphine and indomethacin but was unaffected by rimazolium. Prostaglandin-mediated pain (ACh, ATP, acetic acid writhing) was inhibited by all three types of compound; however, pain reaction where prostaglandins (PGs) are not involved (MgSO4 writhing) was inhibited by rimazolium and morphine, but not (or only slightly) by PG synthesis inhibitors. Gastric lesions produced by indomethacin were depressed by rimazolium and aggravated by morphine. These results suggest different mechanisms of anti-inflammatory and analgesic action of rimazolium, morphine and PG synthesis inhibitors. Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Female; Indomethacin; Leukocytes; Luminescent Measurements; Male; Morphine; Naloxone; Pyrimidinones; Rats; Rats, Inbred Strains; Stomach Ulcer | 1985 |
Morphine potentiates the gastroulcerogenic effect of indometacin in rats.
Morphine potentiated the ulcerogenic activity of indometacin in a dose-dependent manner when administered subcutaneously (2.5-7.5 mg/kg). However, in the case of intracerebroventricular administration, morphine failed to exert any potentiating action. Atropine (0.5 mg/kg, s.c.) and cimetidine (12.5-25 mg/kg, s.c.) decreased the ulcerogenic activity of indometacin, and the combination of indometacin/morphine in about the same degree. However, the reduced ulcerogenic activity of indometacin after atropine or cimetidine treatment could still be enhanced by morphine if it was added to the combination of indometacin/atropine or indometacin/cimetidine. Since the potentiating action of morphine was completely blocked by naloxone (1 mg/kg), this action of morphine might be mediated via opiate receptors. Topics: Animals; Atropine; Cimetidine; Drug Synergism; Female; Gastric Mucosa; Indomethacin; Male; Morphine; Naloxone; Rats; Rats, Inbred Strains; Stomach Ulcer | 1985 |
Effects of morphine and naloxone on restraint-stress ulcers in rats.
Rats were starved for 24 h. Morphine sulphate (1.0, 2.0 or 4.0 mg/kg i.p.) or naloxone-HCl (12.5, 25 or 50 mg/kg i.p.) was administered prior to 3 h of cold-restraint stress. Morphine at 4.0 mg/kg significantly reduced the ulcer severity relative to saline-injected controls and to naloxone-treated rats. Naloxone increased the ulcer incidence and ulcer severity when compared to controls and morphine-treated rats. These results suggest that endogenous opioids released during stress may attenuate the pathological effects of stress. Topics: Animals; Dose-Response Relationship, Drug; Male; Morphine; Naloxone; Rats; Rats, Inbred Strains; Restraint, Physical; Stomach Ulcer; Stress, Physiological | 1985 |
An evaluation of naloxone as a gastric cytoprotective agent during hemorrhagic shock.
Administration of naloxone, an opiate antagonist, is known to improve survival from hemorrhagic shock and to reverse the effects of septicemia on gastric mucosal O2 tension and potential difference (PD). We tested these potentially cytoprotective actions in the ex-vivo canine gastric chamber model with acid, bile, and hemorrhagic hypotension. Naloxone (2 mg/kg IV bolus, then 2 mg/kg/hr IV) was given before or during shock. Naloxone did not affect oxygen consumption, the bile-induced drop in PD, or the transmucosal oxygen consumption, the bile-induced drop in PD, or the transmucosal movements of H+, Na+, K+, and fluid. The reduction in average mucosal lesion formation with naloxone pretreatment (5.4 +/- 1.2 vs. 2.8 +/- 0.5%) was not statistically significant (p = 0.07). Similarly, administration of naloxone after the onset of shock also failed to protect the mucosa from stress ulceration. We conclude: 1) naloxone does not inhibit the effects of topical bile on the gastric mucosal barrier; 2) naloxone has no apparent effect on local gastric vascular resistance during hemorrhagic shock; and 3) the therapeutic potential of naloxone as an anti-ulcer drug is questionable. 24GM 23095 Topics: Acute Disease; Animals; Bile Acids and Salts; Dogs; Drug Evaluation, Preclinical; Female; Gastric Mucosa; Male; Naloxone; Oxygen Consumption; Regional Blood Flow; Shock, Hemorrhagic; Stomach; Stomach Ulcer; Stress, Physiological; Water-Electrolyte Balance | 1984 |
Decreased acid secretion and gastric lesion production by morphine in rats.
The effects of graded doses of morphine on gastric secretion were studied in conscious rats with pyloric occlusion. It was found that, at doses which significantly prolonged the reaction time in the tail-immersion test, morphine significantly decreased both the volume and total acid output of gastric secretion. It was also observed that morphine produced gastric mucosal lesions in a dose-dependent manner. Pretreatment with naloxone 4 mg/kg significantly alleviated the gastric effects of morphine 32 mg/kg. It is suggested that the depressant effects of morphine on gastric secretion and the ulcerogenicity of the narcotic result from its stimulant activity on opiate receptors. Topics: Analgesics; Animals; Gastric Acid; Gastric Mucosa; Male; Morphine; Naloxone; Rats; Rats, Inbred Strains; Stomach Ulcer | 1984 |
Effects of naloxone on serum corticosterone and gastric lesions in stressed rats.
In rats subjected to restraint and exposure to cold, naloxone did not significantly influence the increased serum concentrations of corticosterone or the incidence of stress ulceration, but it significantly reduced the severity of gastric lesions. These findings suggest that endogenous opioids released during stress may contribute to the pathogenesis of stress ulceration. They also support the theory that the adrenocorticosteroids are unimportant aetiological factors in stress ulcer formation. Topics: Animals; Corticosterone; Endorphins; Male; Naloxone; Rats; Rats, Inbred Strains; Stomach Ulcer; Stress, Physiological | 1983 |
Evidence of an involvement of the opioid peptidergic system in the reaction to stressful conditions.
Rats exposed to combined cold and restraint exhibited reduced paw oedema following an injection of carrageenin. Under the same experimental conditions, the local inflammation became fully evident when animals were pretreated with naloxone, 5 mg/kg, s.c. The same dose of the narcotic antagonist also increased the intensity of gastric damage in restrained, cold-exposed rats. On the contrary, gastric ulcerations were practically inexistent in stressed rats treated with 10 mg/kg s.c. of morphine. It is suggested that the opioid peptidergic system is involved in the body's reactivity to stressful stimuli. Topics: Animals; Endorphins; Inflammation; Male; Morphine; Naloxone; Rats; Stomach Ulcer; Stress, Physiological | 1980 |