Metamizol potentiates morphine antinociception but not constipation after chronic treatment.

Abstract:

:This work evaluates the antinociceptive and constipating effects of the combination of 3.2 mg/kg s.c. morphine with 177.8 mg/kg s.c. metamizol in acutely and chronically treated (once a day for 12 days) rats. On the 13th day, antinociceptive effects were assessed using a model of inflammatory nociception, pain-induced functional impairment model, and the charcoal meal test was used to evaluate the intestinal transit. Simultaneous administration of morphine with metamizol resulted in a markedly antinociceptive potentiation and an increasing of the duration of action after a single (298+/-7 vs. 139+/-36 units area (ua); P<0.001) and repeated administration (280+/-17 vs. 131+/-22 ua; P<0.001). Antinociceptive effect of morphine was reduced in chronically treated rats (39+/-10 vs. 18+/-5 au) while the combination-induced antinociception was remained similar as an acute treatment (298+/-7 vs. 280+/-17 au). Acute antinociceptive effects of the combination were partially prevented by 3.2 mg/kg naloxone s.c. (P<0.05), suggesting the partial involvement of the opioidergic system in the synergism observed. In independent groups, morphine inhibited the intestinal transit in 48+/-4% and 38+/-4% after acute and chronic treatment, respectively, suggesting that tolerance did not develop to the constipating effects. The combination inhibited intestinal transit similar to that produced by morphine regardless of the time of treatment, suggesting that metamizol did not potentiate morphine-induced constipation. These findings show a significant interaction between morphine and metamizol in chronically treated rats, suggesting that this combination could be useful for the treatment of chronic pain.

journal_name

Eur J Pharmacol

authors

Hernández-Delgadillo GP,Ventura Martínez R,Díaz Reval MI,Domínguez Ramírez AM,López-Muñoz FJ

doi

10.1016/s0014-2999(02)01344-4

keywords:

subject

Has Abstract

pub_date

2002-04-26 00:00:00

pages

177-83

issue

3

eissn

0014-2999

issn

1879-0712

pii

S0014299902013444

journal_volume

441

pub_type

杂志文章
  • Therapeutic administration of Y-40138, a multiple cytokine modulator, inhibits concanavalin A-induced hepatitis in mice.

    abstract::Concanavalin A-induced hepatitis is often used as a model of liver injury. In this model, plasma tumor necrosis factor-alpha (TNF-alpha) level increased in concanavalin A-injected mice. Prophylactic treatment with Y-40138, N-[1-(4-[4-(pyrimidin-2-yl)piperazin-1-yl]methyl phenyl)cyclopropyl] acetamide.HCl, significantl...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.ejphar.2005.08.060

    authors: Fukuda T,Mogami A,Hisadome M,Komatsu H

    更新日期:2005-10-31 00:00:00

  • The effects of antidepressants and electroconvulsive shocks on the functioning of the mesolimbic dopaminergic system: a behavioral study.

    abstract::The mesolimbic dopaminergic innervation is supposed to be involved in the mechanisms of central effects exerted by various classes of psychotropic drugs. Antidepressants have been found to interact with the brain dopaminergic system as well, although the precise central location of this interaction is unknown. Some da...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章

    doi:10.1016/0014-2999(87)90689-3

    authors: Plaznik A,Kostowski W

    更新日期:1987-03-31 00:00:00

  • NMDA receptor antagonists increase the release of dopamine in the substantia nigra of reserpine-treated rats.

    abstract::Microdialysis of the substantia nigra pars reticulata in freely moving rats disclosed a steady release of dopamine and its metabolites which was greatly reduced after reserpine (4 mg/kg s.c.) and alpha-methyl-p-tyrosine (200 mg/kg i.p.) pretreatments. Local infusion of high K+ (100 mM) or L-3,4-dihydroxyphenylalanine ...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章

    doi:10.1016/0014-2999(95)00837-3

    authors: Biggs CS,Fowler LJ,Whitton PS,Starr MS

    更新日期:1996-03-28 00:00:00

  • Relaxing effects of adenosine in coronary artery in calcium-free medium.

    abstract::Adenosine relaxes the coronary arteries of various species through A2 receptors. The mechanism(s) by which adenosine causes relaxation of the coronary smooth muscle through changes in intracellular Ca levels is not understood. Therefore, the aim of this study was to evaluate the vasodilatory action of adenosine in nor...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章

    doi:10.1016/0014-2999(89)90040-x

    authors: Ramagopal MV,Nakazawa M,Mustafa SJ

    更新日期:1989-01-02 00:00:00

  • Opioidergic and adrenergic modulation of formalin-evoked spinal c-fos mRNA expression and nocifensive behavior in the rat.

    abstract::Fos protein expression has been used to reflect neuronal activation in pain processing pathways although analgesics may uncouple behavioral and Fos responses. We determine whether formalin-induced spinal c-fos mRNA expression (Northern blotting) correlates with nocifensive behavior following pretreatment with morphine...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章

    doi:10.1016/s0014-2999(99)00463-x

    authors: Sawamura S,Fujinaga M,Kingery WS,Belanger N,Davies MF,Maze M

    更新日期:1999-08-27 00:00:00

  • Pharmacological mechanisms of 5-HT₃ and tachykinin NK₁ receptor antagonism to prevent chemotherapy-induced nausea and vomiting.

    abstract::Nausea and vomiting are among the most common and distressing consequences of cytotoxic chemotherapies. Nausea and vomiting can be acute (0-24h) or delayed (24-72 h) after chemotherapy administration. The introduction of 5-HT(3) receptor antagonists in the 90s was a major advance in the prevention of acute emesis. The...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章,评审

    doi:10.1016/j.ejphar.2012.01.046

    authors: Rojas C,Slusher BS

    更新日期:2012-06-05 00:00:00

  • Effect of insulinotropic agent nateglinide on Kv and Ca(2+) channels in pancreatic beta-cell.

    abstract::Novel insulinotropic agent nateglinide stimulates insulin via binding to sulfonylurea receptor and closing the ATP-dependent K+ (K(ATP)) channels in pancreatic beta-cells, leading to an increase in [Ca(2+)](i) for exocytosis. The voltage-dependent Ca(2+) channel and the delayed rectifier K+ (Kv) channels are also pres...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章

    doi:10.1016/s0014-2999(01)01252-3

    authors: Hu S,Wang S

    更新日期:2001-09-14 00:00:00

  • NMDA receptor antagonists suppress behaviors but not norepinephrine turnover or locus coeruleus unit activity induced by opiate withdrawal.

    abstract::Pretreatment with the non-competitive NMDA (N-methyl-D-aspartate) antagonist MK801 (0.5, 1.0 mg/kg, s.c.) suppressed the behavioral signs of withdrawal in morphine-dependent rats. However, the same doses of MK801 that suppressed morphine withdrawal also simultaneously produced phencyclidine (PCP)-like behaviors. Pretr...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章

    doi:10.1016/0014-2999(91)90358-w

    authors: Rasmussen K,Fuller RW,Stockton ME,Perry KW,Swinford RM,Ornstein PL

    更新日期:1991-05-02 00:00:00

  • Discovery of a novel neuroprotective compound, AS1219164, by high-throughput chemical screening of a newly identified apoptotic gene marker.

    abstract::We have reported that tacrolimus (FK506), an immunosuppressive drug, and diclofenac, a non-steroidal anti-inflammatory drug, possess different modes of neuroprotective action. FK506 suppresses only thapsigargin-induced apoptosis in neuroblastoma SH-SY5Y cells while diclofenac reverses tunicamycin-induced as well as th...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.ejphar.2011.07.027

    authors: Yamazaki T,Muramoto M,Okitsu O,Morikawa N,Kita Y

    更新日期:2011-11-01 00:00:00

  • The masking role of the sodium pump and chloride ions on the effect of carbachol in- and outside the endplate region of rat diaphragm muscle.

    abstract::The effect of carbachol (10(-3)M) on the membrane potential of rat diaphragm muscle fibres near and remote from the endplate has been investigated by means of a microelectrode technique. In the endplate region a rather slow depolarization was observed followed by spontaneous repolarization. Outside the endplate region...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章

    doi:10.1016/0014-2999(76)90035-2

    authors: Mooij JJ,Evers CD,Ras R

    更新日期:1976-06-01 00:00:00

  • Bazedoxifene exhibits anti-inflammation and anti-atherosclerotic effects via inhibition of IL-6/IL-6R/STAT3 signaling.

    abstract::Atherosclerosis is regarded as chronic inflammatory disease. The IL-6/STAT3 pathway plays an important role in inflammation. We previously described a small-molecule compound, Bazedoxifene, which target IL-6/STAT3 pathway and has been approved for clinical use for osteoporosis in postmenopausal women. The aim of this ...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.ejphar.2020.173822

    authors: Luo P,Wang Y,Zhao C,Guo J,Shi W,Ma H,Liu T,Yan D,Huo S,Wang M,Li C,Lin J,Li S,Lv J,Zhang C,Lin L

    更新日期:2021-02-15 00:00:00

  • Evidence for a role of nitric oxide in the corticotropin-releasing factor release induced by interleukin-1 beta.

    abstract::Interleukin-1 beta stimulates corticotropin-releasing factor (CRF) secretion from the hypothalamus involving the activation of prostaglandins. This study investigated the possibility that nitric oxide (NO) acts as a mediator of interleukin-1-induced CRF release. An in vitro rat hypothalami continuous perifusion system...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章

    doi:10.1016/0014-2999(94)00700-h

    authors: Sandi C,Guaza C

    更新日期:1995-02-14 00:00:00

  • Dopamine D3 receptor modulation of dopamine efflux in the rat nucleus accumbens.

    abstract::The effect of antipsychotics on electrically evoked dopamine efflux in the rat nucleus accumbens core and shell was investigated, using in vitro fast cyclic voltammetry. In the nucleus accumbens core, the dopamine D2/D3 receptor agonist, (+/-)7-OH-DPAT ((+/-)-2-dipropylamino-7-hydroxy-1,2,3,4-tetrahydronaphthalene), i...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.ejphar.2006.01.014

    authors: Roberts C,Cummins R,Gnoffo Z,Kew JN

    更新日期:2006-03-18 00:00:00

  • Potentiation by amino acid of the therapeutic effect of highly purified vitamin B2 in mice with lipopolysaccharide-induced shock.

    abstract::The aim of this experiment was to clarify whether an amino acid supplement could enhance the therapeutic effect of vitamin B2 (riboflavin 5'-sodium phosphate; purity > 97%) in mice with lipopolysaccharide-induced shock. Six hours after injection of a lethal dose of lipopolysaccharide, treatment (6-h i.v. infusion) was...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.ejphar.2004.04.019

    authors: Toyosawa T,Suzuki M,Kodama K,Araki S

    更新日期:2004-06-16 00:00:00

  • Effects of propranolol on regional myocardial blood flow and function during severe coronary stenosis in dogs.

    abstract::The effects of propranolol alone or associated with atrial pacing were studied on regional myocardial blood flows (RMBF) and regional contractility (sonocardiometry) in non-ischemic, moderately and severely ischemic areas of the canine myocardium. In non-ischemic areas, propranolol reduced both epicardial and endocard...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章

    doi:10.1016/0014-2999(83)90284-4

    authors: Thuillez C,Berdeaux A,Bonhenry C,Duhaze P,Giudicelli JF

    更新日期:1983-09-02 00:00:00

  • Factors affecting the transition of acute kidney injury to chronic kidney disease: Potential mechanisms and future perspectives.

    abstract::Acute kidney injury (AKI) is defined as a rapid loss of kidney function characterised by inflammation and cell death, ultimately leading to further functional and structural renal alterations. Based on experimental and epidemiological pieces of evidence, AKI may progress to chronic kidney disease (CKD) even after a re...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章,评审

    doi:10.1016/j.ejphar.2019.172711

    authors: Ogbadu J,Singh G,Aggarwal D

    更新日期:2019-12-15 00:00:00

  • Antipyretic activity of cinnamyl derivatives and related compounds in influenza virus-infected mice.

    abstract::Kakkon-to is composed of seven medicinal herbs and exhibited novel antipyretic activity by suppressing interleukin-1alpha production responsive to interferon in a murine intranasal influenza virus infection model. Using this model, antipyretic compounds with such novel biological activities were characterized from the...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章

    doi:10.1016/s0014-2999(98)00121-6

    authors: Kurokawa M,Kumeda CA,Yamamura J,Kamiyama T,Shiraki K

    更新日期:1998-05-01 00:00:00

  • The thyrotropin-releasing hormone-like peptides pGlu-Phe-Pro amide and pGlu-Glu-Pro amide increase plasma triiodothyronine levels in the mouse; the activity is sensitive to testosterone.

    abstract::Three naturally occurring peptides, pGlu-Glu-Pro amide, pGlu-Phe-Pro amide and pGlu-Gln-Pro amide, with similar structures to thyrotropin releasing hormone (TRH) have recently been identified but no studies of their in vivo activities have been reported previously. We describe here the ability of pGlu-Phe-Pro amide an...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章

    doi:10.1016/s0014-2999(98)00593-7

    authors: Cremades A,Peñafiel R,Rausell V,Del Rio-Garcia J,Smyth DG

    更新日期:1998-09-25 00:00:00

  • Studies on the role of 5-HT2C and 5-HT2B receptors in regulating generalised seizure threshold in rodents.

    abstract::The present studies were conducted to investigate the role of 5-HT2C and 5-HT2B receptors in the generation of pentylenetetrazol and electroshock-evoked seizures. The 5-HT2C/2B receptor-preferring agonist 1-(m-chlorophenyl)-piperazine (mCPP; 2.5-7 mg/kg i.p.) weakly elevated seizure threshold in the mouse (but not the...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章

    doi:10.1016/s0014-2999(98)00621-9

    authors: Upton N,Stean T,Middlemiss D,Blackburn T,Kennett G

    更新日期:1998-10-16 00:00:00

  • Contribution of supraspinal mu- and delta-opioid receptors to antinociception in the rat.

    abstract::This study evaluated the contribution of supraspinal opioid receptors to the production of antinociception, in the rat. I.c.v. administration of a selective mu- (DAMGO) and a selective delta- (DPDPE), but not a selective kappa- (U50,488H) opioid receptor agonist, produced significant dose-dependent increase in mechani...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章

    doi:10.1016/0014-2999(91)90905-6

    authors: Miaskowski C,Taiwo YO,Levine JD

    更新日期:1991-12-03 00:00:00

  • The neuronal KCNQ channel opener retigabine inhibits locomotor activity and reduces forebrain excitatory responses to the psychostimulants cocaine, methylphenidate and phencyclidine.

    abstract::Many central stimulating drugs have a pronounced stimulatory effect on striatal and cortical activity which is associated to enhanced function of mesencephalic dopaminergic neurons. Mesencephalic KCNQ (also termed K(v)7) potassium channels suppress the basal activity of dopaminergic neurons in the substantia nigra and...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.ejphar.2007.05.029

    authors: Hansen HH,Andreasen JT,Weikop P,Mirza N,Scheel-Krüger J,Mikkelsen JD

    更新日期:2007-09-10 00:00:00

  • Levocetirizine ameliorates high fructose diet-induced insulin resistance, vascular dysfunction and hepatic steatosis in rats.

    abstract::This study investigates the possible protective effects of levocetirizine against fructose-induced insulin resistance, hepatic steatosis and vascular dysfunction, in comparison to pioglitazone, a standard insulin sensitizer. Male Sprague Dawley rats (150-200 g) were divided into 4 groups. Three groups were fed on high...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.ejphar.2014.07.021

    authors: Shawky NM,Shehatou GS,Abdel Rahim M,Suddek GM,Gameil NM

    更新日期:2014-10-05 00:00:00

  • Increased resting Ca2+ maintains the myogenic tone and activates K+ channels in arteries from young spontaneously hypertensive rats.

    abstract::We examined whether the Ca2+ channel function in the resting state alters the resting tone in femoral and carotid arteries from spontaneously hypertensive rats (SHR) at early hypertensive stages (6 and 4 weeks of age), and data were compared with findings in age-matched normotensive Wistar-Kyoto rats (WKY). Strips of ...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章

    doi:10.1016/0922-4106(93)90198-i

    authors: Asano M,Matsuda T,Hayakawa M,Ito KM,Ito K

    更新日期:1993-11-15 00:00:00

  • Mechanisms underlying the inhibitory effect of dibutyryl cyclic AMP in vascular smooth muscle.

    abstract::The mechanism by which dibutyryl cyclic AMP (db-cAMP) induces vasodilatation was examined in isolated rat aorta. The contraction induced by norepinephrine (NE) was more sensitive to the inhibitory effect of db-cAMP than that induced by high K+, and the contraction induced by lower concentrations of each stimulant was ...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章

    doi:10.1016/0014-2999(92)90385-h

    authors: Abe A,Karaki H

    更新日期:1992-02-18 00:00:00

  • Comparison of clenbuterol enantiomers using four psychopharmacological tests sensitive to beta-agonists.

    abstract::The effects of the enantiomers of clenbuterol were compared in four psychopharmacological tests in which beta-adrenergic agonists are known to be active. In mice (+/-)-clenbuterol 0.06 mg/kg decreased motor activity and antagonized the hypothermia induced by 16 mg/kg of apomorphine; at 0.5 mg/kg it increased head-twit...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章

    doi:10.1016/0014-2999(85)90481-9

    authors: Martin P,Puech AJ,Brochet D,Soubrié P,Simon P

    更新日期:1985-10-29 00:00:00

  • Inhibitory effect of ethanol on the 5-hydroxytryptamine-induced Bezold-Jarisch reflex--involvement of peripheral 5-HT3 receptors.

    abstract::The influence of ethanol (0.5, 1.0 and 2.0 g/kg i.p.) on the Bezold-Jarisch reflex in urethane-anaesthetized rats was studied. 5-Hydroxytryptamine (serotonin; 5-HT; 1, 3, 10 and 30 micrograms/kg i.v.) and capsaicin (1, 3 and 10 micrograms/kg i.v.) reflexly decreased heart rate in a dose-dependent manner. The 5-HT3 rec...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章

    doi:10.1016/0926-6917(95)90020-9

    authors: Malinowska B,Göthert M,Godlewski G,Wróbel B,Bönisch H,Buczko W

    更新日期:1995-05-26 00:00:00

  • The discriminative stimulus properties of cocaine: effects of BAY K 8644 and nimodipine.

    abstract::Calcium channel blockers appear to reduce the cardiac toxicity of cocaine and some stimulant-induced behaviors. The present experiment was designed to test whether the internal state induced by cocaine is altered by the calcium antagonist nimodipine. Substitution tests with the calcium agonist BAY K 8644 were also con...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章

    doi:10.1016/0014-2999(90)94072-6

    authors: Callahan PM,Cunningham KA

    更新日期:1990-09-04 00:00:00

  • Homologous desensitization of the effects of endothelin on rabbit aorta rings and on cultured rat aorta smooth muscle cells.

    abstract::The effects of endothelin-1 on normal and everted rabbit aorta rings and on cultured rat aortic smooth muscle cells were studied. Endothelin-1 (40 nM) contracted both normal and everted rings, and was still able to induce a prolonged contraction in Ca2(+)-free medium. Treatment of cultured cells with 100 nM endothelin...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章

    doi:10.1016/0014-2999(90)90412-y

    authors: Miasiro N,Paiva AC

    更新日期:1990-04-10 00:00:00

  • Myosin phosphorylation and Ca2+ sensitization in porcine coronary arterial smooth muscle stimulated with endothelin-1.

    abstract::We examined the mechanism of endothelin-1-induced contraction in the porcine coronary artery by assessing the changes in myosin light chain phosphorylation and cytosolic Ca2+ concentration ([Ca2+]i) determined by fura-2 and front-surface fluorometry. Endothelin-1 induced a rapid phosphorylation of myosin both in the p...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章

    doi:10.1016/0922-4106(94)90011-6

    authors: Kodama M,Yamamoto H,Kanaide H

    更新日期:1994-12-15 00:00:00

  • Bortezomib influences the expression of malignant plasma cells membrane antigens.

    abstract::Multiple myeloma cells can be characterized immunophenotypically as the expression levels of several membrane antigens differ from those of normal plasma cells. These antigens are important for making a diagnostic of multiple myeloma; they have a significant role in survival and proliferation of multiple myeloma cells...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章

    doi:10.1016/j.ejphar.2013.02.002

    authors: Tagoug I,Plesa A,Dumontet C

    更新日期:2013-04-15 00:00:00