naloxone and Peritonitis

Eugenia pohliana DC.(Myrtaceae) is used in folk medicine by communities in Brazil. However, there are no reports on its biological activity. This is the first study to identify the components of E. pohliana essential oil (EpEO) and evaluate their antinociceptive and anti-inflammatory activities in an in vivo model at doses of 25, 50, and 100 mg/kg. The essential oil (EO) was obtained by hydrodistillation, and the analysis was performed by gas chromatography coupled with mass spectrometry. Antinociceptive activity was evaluated by writhing tests, tail movement, and formalin (neurogenic and inflammatory pain); naloxone was used to determine the nociception mechanism. Anti-inflammatory activity was assessed by oedema and peritonitis tests. We found that (E)-β-caryophyllene (BCP) (15.56%), δ-cadinene (11.24%) and α-cadinol (10.89%) were the major components. In the writhing test, there was a decrease in writing by 42.95-70.70%, in the tail movement, an increase in latency time by 69.12-86.63%, and in the formalin test, there was a reduction in pain neurogenic by 29.54-61.74%, and inflammatory pain by 37.42-64.87%. The antinociceptive effect of EpEO occurs through the activation of opioid receptors. In addition, a reduction in inflammation by 74.93‒81.41% was observed in the paw edema test and inhibition of the influx of leukocytes by 51.86‒70.38% and neutrophils by 37.74‒54.72% in the peritonitis test. It was concluded that EpEO has antinociceptive effect by the opioid pathway, as shown by the inhibitory effect of naloxone, and anti-inflammatory actions, and that its use does not cause hemolytic damage or behavioral change.

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Edema; Eugenia; Inflammation; Mice; Myrtaceae; Naloxone; Nociception; Oils, Volatile; Pain; Peritonitis; Plant Extracts

Byrsonima intermedia A. Juss. is popularly known as "murici pequeno" and is native to the Brazilian Cerrado. This species has been used as an antimicrobial, anti-hemorrhagic, anti-diarrheal and anti-inflammatory. Nevertheless, scientific information regarding Byrsonima intermedia is limited; there are no reports related to its possible anti inflammatory and antinociceptive effects. This study employed in vivo inflammatory and nociceptive models to evaluate the scientific basis for the traditional use of Byrsonima intermedia.. Carrageenan-induced paw edema, peritonitis and fibrovascular tissue growth induced by s.c. cotton pellet implantation tests were used to investigate the anti-inflammatory activity of Byrsonima intermedia aqueous extract (BiAE) in rats. Mechanical nociceptive paw, formalin and hot plate tests were used to evaluate the antinociceptive activity in mice. High-performance liquid chromatography (HPLC), phytochemistry screening and determination of total phenolics and flavonoids were used to determine the chemical profile of the BiAE.. BiAE at test doses of 30-300 mg/kg p.o. clearly demonstrated anti-inflammatory effects by reduced carrageenan-induced paw edema, by inhibited leukocyte recruitment into the peritoneal cavity and, in the model of chronic inflammation, by using the cotton pellet-induced fibrovascular tissue growth in rats. The extracts at test doses of 30-300 mg/kg p.o. clearly demonstrated antinociceptive activity in all tests. Administration of the opioid receptor antagonist naloxone completely inhibited the antinociceptive effect induced by BiAE (100 mg/kg).. BiAE markedly exhibits anti-inflammatory action in rats and antinociceptive activity in mice. Thus, it may be useful in the treatment of inflammatory hyperalgesic disorders, which supports previous claims of its traditional use.

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Behavior, Animal; Carrageenan; Chromatography, High Pressure Liquid; Cotton Fiber; Disease Models, Animal; Dose-Response Relationship, Drug; Edema; Flavonoids; Formaldehyde; Granuloma, Foreign-Body; Hot Temperature; Lipopolysaccharides; Male; Malpighiaceae; Mice; Motor Activity; Naloxone; Narcotic Antagonists; Pain; Pain Measurement; Pain Threshold; Peritonitis; Phenols; Plant Bark; Plant Extracts; Plant Stems; Plants, Medicinal; Rats; Rats, Wistar; Time Factors

This paper describes the synthesis of new cyclic imides obtained by reaction with aminophenazone (CAS 58-15-1, 4-aminoantipyrine) and different anhydrides with further cyclization with acetic acid under reflux. Their structures were confirmed by spectral data (IR and NMR) and elemental analysis. The analgesic activity of the synthesized compounds was investigated initially with the writhing test in mice and the most promising compound, a 3,4-dichloromaleimide derivative (3), was analyzed using other models of nociception. The results indicated that compound 3 exerts potent analgesic activity in mice, being more active than some reference drugs. The analgesia caused by this compound was not reversed by naloxone in the writhing test. In the hotplate test, compound 3 did not increase the latency period of pain induced by thermal stimuli, confirming that it does not interact with opioid systems.

Topics: Acetic Acid; Aminopyrine; Analgesics, Non-Narcotic; Animals; Capsaicin; Formaldehyde; Imides; Indicators and Reagents; Male; Mice; Naloxone; Narcotic Antagonists; Pain; Pain Measurement; Peritonitis; Reaction Time; Structure-Activity Relationship

The pharmacological activity of phenylacetyl-Phe-Ser-Arg-N-(2, 4-dinitrophenyl)-ethylenediamine (TKI), a tissue kallikrein specific inhibitor, was assessed using models of nociception and inflammation in mice. Injection of TKI (13.6 - 136 micromol kg(-1), i.p. or 41 - 410 micromol kg(-1), s.c.) produced a dose-related inhibition of the acetic acid-induced writhes (by 37 to 85% or 34 to 80%, respectively). The antinociceptive activity of TKI (41 micromol kg(-1), i.p.) was maximal after 30 min injection and lasted for 120 min. The effect was unaltered by pretreatment with naloxone (8.2 micromol kg(-1), s.c.) or bilateral adrenalectomy. TKI (41 and 136 micromol kg(-1), i.p.) produced a dose-related decrease of the late phase of formalin-induced nociception by 79 and 98%, respectively. At 136 micromol kg(-1), i.p., TKI also shortened the duration of paw licking in the early phase by 69%. TKI (41 and 136 micromol kg(-1), i.p.) also reduced the capsaicin-induced nociceptive response (by 51 to 79%). TKI (41 micromol kg(-1), i.p. or 410 micromol kg(-1), s.c.) reduced the oedematogenic response, from the second to the fifth hour after carrageenin injection by 36 to 30% or by 47 to 39%, respectively. Pretreatment with TKI (41 micromol kg(-1), i.p.) reduced the capsaicin-induced neurogenic inflammation in the mouse ear by 54%. It is concluded that TKI presents antinociceptive and antiinflammatory activities mediated by inhibition of kinin formation by tissue kallikrein in mice. The results also indicate that the tissue kallikrein-dependent pathway contributes to kinin generation in nociceptive and inflammatory processes in mice.

Topics: Adrenalectomy; Analgesics, Non-Narcotic; Animals; Anti-Inflammatory Agents, Non-Steroidal; Edema; Enzyme Inhibitors; Female; Inflammation; Kinins; Male; Mice; Naloxone; Oligopeptides; Pain; Peritonitis; Tissue Kallikreins

Intraperitoneal (i.p.) injection of adult goldfish with 3% thioglycollate (TG) induces an acute peritoneal inflammation connected with a massive influx of inflammatory leukocytes mainly of the head kidney origin. The number of peritoneal exudate cells retrieved on day 2 of the inflammatory response is significantly lower in fish injected with TG and morphine (20 mg/kg b.w.) than in animals injected with TG only. The morphine effect was totally antagonized in fish injected 20 min earlier with naltrexone (1 mg/kg), a well-known blocker of opioid receptors. Light microscopy of the head kidney Epon sections revealed that basophilic granulocytes are common in the control PBS-injected fish and even more frequent in fish injected with morphine only. In sharp contrast basophils are very rare in the head kidneys from animals with the TG-induced peritoneal inflammation, while they are more numerous in fish injected with TG and morphine. Supposedly, the basophilic granulocytes might be involved in the inhibitory effects of morphine on the acute inflammation in goldfish. An involvement of the head kidney in the morphine modulation of the inflammatory response is strongly supported by the detection of opioid receptors in the head kidney cells suspension.

Topics: Analgesics, Opioid; Animals; Binding Sites; Drug Interactions; Goldfish; Kidney; Kinetics; Leukocytes; Morphine; Naloxone; Narcotic Antagonists; Peritoneal Cavity; Peritonitis; Radioligand Assay; Receptors, Opioid; Thioglycolates

Fedotozine is a peripheral opioid agonist. Its effects were assessed in experimental ileus in rats.. Ileus was induced by abdominal surgery (laparotomy and cecum palpation) or peritonitis (acetic acid, intraperitoneally). Digestive motility was recorded by electromyography and gastrointestinal transit estimated using a 51Cr-labeled test meal.. Surgery or peritonitis inhibited motility and migrating myoelectrical complexes for 2-3 hours. In both models, fedotozine (3 mg/kg, intravenously; 10 mg/kg, subcutaneously) restored a normal motility pattern. This action was reproduced by the kappa-agonist, U-50, and 488H and was blocked by subcutaneous naloxone, naloxone-methiodide, or nor-binaltorphimine, a selective kappa-antagonist. Peritonitis induced a 57% inhibition of gastric emptying and intestinal transit that was reversed by fedotozine (1-10 mg/kg, subcutaneously) or kappa-agonists (U-50, 488H, bremazocine) but not delta-agonists (DPDPE, [D-Ala2]-deltorphin-II), whereas mu-agonists (morphine, fentanyl) potentiated ileus. Fedotozine restoration of transit was blocked by subcutaneous naloxone, naloxone-methiodide, or norbinaltorphimine but not by intracerebroventricular naloxone. Fedotozine was inactive up to 300 micrograms/rat when given intracerebroventrically or intrathecally.. Fedotozine reverses experimental ileus via an action at peripheral kappa-opioid receptors.

Topics: 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; Abdomen; Animals; Benzyl Compounds; Gastric Emptying; Gastrointestinal Motility; Intestinal Obstruction; Male; Naloxone; Peritonitis; Propylamines; Pyrrolidines; Rats; Rats, Sprague-Dawley; Receptors, Opioid, kappa

To explain the high neonatal mortality from peritonitis-induced septic shock despite current resuscitation practices, the efficacy of dopamine, naloxone, and prostacyclin was evaluated in an experimental neonatal model. Hemodynamics were monitored and survival was measured in anesthetized neonatal swine, which were subjected to fatal fecal-Escherichia coli peritonitis-induced septic shock. All the animals received fluid resuscitation, antibiotics, and bicarbonate to correct acidosis. Pharmacologic resuscitation began when cardiac output dropped below baseline in the experimental groups. Although significant differences were observed between groups in cardiac output, mean arterial and mean pulmonary arterial pressures, left ventricular stroke work, stroke volume, and pulmonary vascular resistance indices (P less than 0.02), and each animal exhibited favorable hemodynamic responses during the first several hours of dopamine and naloxone infusion, these drugs failed to prolong survival. Also, 5 of the 9 naloxone-treated pigs (56%), died with histologically proven intestinal ischemia (P less than 0.02). Thus, dopamine, naloxone, and prostacyclin (at doses commonly recommended for the treatment of septic shock) fail to positively influence the fatal course of this condition, and the use of naloxone in this model is associated with profound intestinal ischemia.

Topics: Analysis of Variance; Animals; Animals, Newborn; Dopamine; Drug Evaluation; Epoprostenol; Escherichia coli Infections; Feces; Hemodynamics; Intestinal Perforation; Naloxone; Peritonitis; Resuscitation; Shock, Septic; Swine; Time Factors