Enhancement of Antinociception but not Constipation by Combinations Containing Tramadol and Metamizole in Arthritic Rats

López‐Muñoz, Francisco; Moreno-Rocha, Luis Alfonso; Bravo, Gerardo Ferrando; Guevara-López, Uriah; Domínguez-Ramírez, Adriana Miriam; Déciga-Campos, Myrna

doi:10.1016/j.arcmed.2013.09.004

Cited by 8 publications

(10 citation statements)

References 33 publications

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“…The combination of metamizol and tramadol (177.8 + 17.8 mg/kg) was selected from a total of 25 combinations studied (López-Muñoz et al, 2013a) because this proportion gives an adequate antinociceptive effect and presents fewer side effects than other combinations. The results obtained after administration of the combination of metamizol and tramadol after a single dose, confirmed the potentiation of the antinociceptive effect elicited by the drugs given alone ( P < 0.05).…”

Section: Discussionmentioning

confidence: 99%

“…Metamizol and tramadol are analgesic drugs with complex mechanisms of action, extensively used in combination in the management of acute postoperative pain in humans (Poveda et al, 2003). The pharmacodynamic mechanism for the interaction between metamizol and tramadol could be attributed partially to their participation in the opioidergic system (Vasquez and Vanegas, 2000, López-Muñoz et al, 2013a). Other mechanisms such as the l -arginine-NO-cyclic GMP pathway and interaction with N-methyl d -aspartic acid receptors could be proposed to explain the antinociceptive synergism observed with the combination of such drugs.…”

Section: Introductionmentioning

confidence: 99%

“…Other mechanisms such as the l -arginine-NO-cyclic GMP pathway and interaction with N-methyl d -aspartic acid receptors could be proposed to explain the antinociceptive synergism observed with the combination of such drugs. In a previous study, 25 different combinations of metamizol and tramadol were analyzed using the model of “pain-induced functional impairment in rat” (PIFIR) after a single dose administration, and the results as antinociceptive effects were additive or potentiative, for all the combinations studied (López-Muñoz et al, 2013a).…”

Section: Introductionmentioning

confidence: 99%

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Effect of tramadol on metamizol pharmacokinetics and pharmacodynamics after single and repeated administrations in arthritic rats

Moreno-Rocha

López‐Muñoz

López

et al. 2016

Saudi Pharmaceutical Journal

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Combined administration of certain doses of opioid compounds with a non-steroidal anti-inflammatory drug can produce additive or supra-additive effects while reducing unwanted effects. We have recently reported that co-administration of metamizol with tramadol produces antinociceptive effect potentiation, after acute treatment. However, none information about the effect produced by the combination after chronic or repeated dose administration exists. The aims of this study were to investigate whether the antinociceptive synergism produced by the combination of metamizol and tramadol (177.8 + 17.8 mg/kg, s.c. respectively) is maintained after repeated treatment and whether the effects observed are primarily due to pharmacodynamic interactions or may be related to pharmacokinetics changes. Administration of metamizol plus tramadol acute treatment significantly enhanced the antinociceptive effect of the drugs given alone ( < 0.05). Nevertheless, this effect decreased about 53% after the chronic treatment (3 doses per day, for 4 days). No pharmacokinetic interaction between metamizol and tramadol was found under acute treatment ( > 0.05). The mechanism involved in the synergism of the antinociceptive effect observed with the combination of metamizol and tramadol in single dose cannot be attributed to a pharmacokinetic interaction, and other pharmacodynamic interactions have to be considered. On the other hand, when metamizol and tramadol were co-administered under repeated administrations, a pharmacokinetic interaction and tolerance development occurred. Differences found in metamizol active metabolites' pharmacokinetics ( < 0.05) were related to the development of tolerance produced by the combination after repeated doses. This work shows an additional preclinical support for the combination therapy. The clinical utility of this combination in a suitable dose range should be evaluated in future studies.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Effect of tramadol on metamizol pharmacokinetics and pharmacodynamics after single and repeated administrations in arthritic rats

Moreno-Rocha

López‐Muñoz

López

et al. 2016

Saudi Pharmaceutical Journal

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“…No unchanged MET was detected in the samples analysed, since it is immediately hydrolysed to its major active metabolite MAA, which is known to have antinociceptive activity in the ‘tail‐flick’ model and the PIFIR model …”

Section: Resultsmentioning

confidence: 99%

“…Previously, it was demonstrated that the antinociceptive effect of the combination of morphine (MOR) and metamizol (MET), 5.6 + 562.3 mg/kg s.c. respectively, was significantly higher than that observed with the drugs administered individually at the same doses in arthritic rats, either after single or chronic treatments . In this case, the pharmacodynamic mechanism for the interaction between MOR and MET was partially attributed to opioidergic system participation . Other mechanisms such as the l ‐arginine‐NO‐cyclic GMP pathway and interaction with N ‐methyl d ‐aspartic acid receptors were proposed to explain the synergism and the delay in the development of tolerance observed with the combination of such drugs.…”

Section: Introductionmentioning

confidence: 80%

Pharmacokinetics and pharmacodynamics of metamizol in co-administration with morphine under acute and chronic treatments in arthritic rats

Carrillo-Calzadilla

López‐Muñoz

Moreno-Rocha

et al. 2017

Journal of Pharmacy and Pharmacology

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The mechanism involved in the potentiation of the antinociceptive effect produced by the combination, cannot be explained by the interaction of morphine on metamizol pharmacokinetics. Other pharmacokinetic interactions along with known pharmacodynamic interactions in which metamizol active metabolites contribute, should be considered. The frequency of administration enhances tolerance development and induces metamizol elimination process.

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Antinociceptive Interactions Between Meloxicam and Gabapentin in Neuropathic Pain Depend on the Ratio used in Combination in Rats

Espinosa-Juárez

Jaramillo-Morales

Corona-Ramos

et al. 2016

Drug Development Research

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Preclinical Research Neuropathic pain is particularly difficult to treat because of its diverse etiologies and underlying pathophysiological mechanisms. Drug combinations have been proposed to effectively treat some neuropathies. In the present study the interaction of five combinations of meloxicam and gabapentin, were studied to assess the possible synergistic antinociceptive response in neuropathic pain using the von Frey and acetone tests in rat models. Coadministration of meloxicam and gabapentin increased the antihyperalgesic or antiallodynic effects as compared with the compounds administered alone. The area under the curve (AUC) of the antihyperalgesic effects produced by the combination of the two drugs was generally similar to the theoretical sum of effects produced by each drug alone. However, the AUC of the antiallodynic effect produced by one combination (meloxicam 1.0 mg/kg + gabapentin 10 mg/kg) was greater than the theoretical sum of the effects produced by each drug alone. The type of final interaction on the drug combinations can be additive or cause potentiation of antinociceptive effects and depends on the proportion of each compound used in dosing. Drug Dev Res 77 : 134-142, 2016. © 2016 Wiley Periodicals, Inc.

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Enhancement of Antinociception but not Constipation by Combinations Containing Tramadol and Metamizole in Arthritic Rats

Cited by 8 publications

References 33 publications

Effect of tramadol on metamizol pharmacokinetics and pharmacodynamics after single and repeated administrations in arthritic rats

Effect of tramadol on metamizol pharmacokinetics and pharmacodynamics after single and repeated administrations in arthritic rats

Pharmacokinetics and pharmacodynamics of metamizol in co-administration with morphine under acute and chronic treatments in arthritic rats

Antinociceptive Interactions Between Meloxicam and Gabapentin in Neuropathic Pain Depend on the Ratio used in Combination in Rats

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