The antinociceptive efficacy of morphine, metamizol, or their combination in an experimental rat model with different levels of inflammatory pain

López‐Muñoz, Francisco; Godínez‐Chaparro, Beatriz; Huerta-Cruz, Juan Carlos; Guevara-López, Uriah; Domínguez-Ramírez, Adriana Miriam; Cortés-Arroyo, Alma Rosa

doi:10.1016/j.pbb.2008.07.007

Cited by 10 publications

(11 citation statements)

References 31 publications

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“…This is also true for metamizole, as it has been proven that co-administration of metamizole with morphine (López-Muñ oz et al 2008, Domtnguez-Ramtrez et al 2010, paracetamol or ketoprofen (Oberhofer et al 2005) is able to produce potentiation of antinociceptive effects. Domínguez-Ramírez et al (2010) demonstrated that co-administration of morphine and metamizole under acute treatment produced a significantly higher antinociceptive effect than that obtained with morphine alone.…”

Section: Interactions With Other Analgesicsmentioning

confidence: 94%

“…Combinations of analgesic drugs with different mechanisms of action may produce effective analgesia and limit side effects by reducing doses of one or both compounds (López-Muñ oz et al 2008). This is also true for metamizole, as it has been proven that co-administration of metamizole with morphine (López-Muñ oz et al 2008, Domtnguez-Ramtrez et al 2010, paracetamol or ketoprofen (Oberhofer et al 2005) is able to produce potentiation of antinociceptive effects.…”

Section: Interactions With Other Analgesicsmentioning

confidence: 99%

“…Over recent years, they have gained popularity as a medication to relieve postoperative pain; used alone to stop mild to moderate pains, but even more importantly as a component of multimodal analgesia (Schug and Manopas 2007). Very good effects have been attained in treatment of acute pain using metamizole in combination with NSAIDs, including ketoprofen (Oberhofer et al 2005) or with opioid analgesics (López-Muñ oz et al 2008, Baumgartner et al 2009). The efficacy of metamizole in post-operative pain therapy has been confirmed in studies conducted on humans (Edwards et al 2001, Chaparro et al 2012) and on animals (Imagawa et al 2011).…”

Section: Clinical Applications In Peoplementioning

confidence: 99%

“…Thus, most probably the potentiation of morphine antinociception by metamizole originates not only from the interaction at the pharmacodynamic level, but also from the modification of the pharmacokinetics of morphine. An experiment conducted by López-Muñ oz et al (2008) implies that the synergism between metamizole and morphine is of a superadditive nature; these researchers demonstrated that co-administration of the two drugs ensured a potentiated and better antinociceptive effect than each drug given individually or their expected theoretical aggregated effects. This finding verifies the existence of some superadditive synergism between metamizole and morphine.…”

Section: Interactions With Other Analgesicsmentioning

confidence: 99%

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Pharmacological characteristics of metamizole

Jasiecka¹,

Maślanka²,

Jaroszewski³

2014

Polish Journal of Veterinary Sciences

126

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Metamizole (dipyrone) is a popular analgetic, non-opioid drug, commonly used in human and veterinary medicine. In some cases, this agent is still incorrectly classified as a non-steroidal anti-inflammatory drug (NSAID). Metamizole is a pro-drug, which spontaneously breaks down after oral administration to structurally related pyrazolone compounds. Apart from its analgesic effect, the medication is an antipyretic and spasmolytic agent. The mechanism responsible for the analgesic effect is a complex one, and most probably rests on the inhibition of a central cyclooxygenase-3 and activation of the opioidergic system and cannabinoid system. Metamizole can block both PG-dependent and PG-independent pathways of fever induced by LPS, which suggests that this drug has a profile of antipyretic action distinctly different from that of NSAIDs. The mechanism responsible for the spasmolytic effect of metamizole is associated with the inhibited release of intracellular Ca 2+ as a result of the reduced synthesis of inositol phosphate. Metamizole is predominantly applied in the therapy of pain of different etiology, of spastic conditions, especially affecting the digestive tract, and of fever refractory to other treatments. Co-administration of morphine and metamizole produces superadditive, antinociceptive effects. Metamizole is a relatively safe pharmaceutical preparation although it is not completely free from undesirable effects. Among these side-effects, the most serious one that raises most controversy is the myelotoxic effect. It seems that in the past the risk of metamizole-induced agranulocytosis was exaggerated. Despite the evidence showing no risk of teratogenic and embryotoxic effects, the drug must not be administered to pregnant women, although it is allowed to be given to pregnant and lactating animals. This paper seeks to describe the characteristics of metamizole in the light of current knowledge.

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Section: Interactions With Other Analgesicsmentioning

confidence: 94%

Section: Interactions With Other Analgesicsmentioning

confidence: 99%

Section: Clinical Applications In Peoplementioning

confidence: 99%

Section: Interactions With Other Analgesicsmentioning

confidence: 99%

See 2 more Smart Citations

Pharmacological characteristics of metamizole

Jasiecka¹,

Maślanka²,

Jaroszewski³

2014

Polish Journal of Veterinary Sciences

126

View full text Add to dashboard Cite

show abstract

“…Opioid receptors are among the most important systems which modulate nociception and antinociception, these receptors being distributed in many regions of the CNS (Mao, 1999). In this regard, the antinociceptive effect of morphine as a known agonist of mu opioid receptors and the role of these receptors in modulating nociception have been documented (de Lima et al ., 2009; Lopez‐Munoz et al ., 2008; Yoon et al ., 2008).…”

Section: Discussionmentioning

confidence: 99%

Silymarin potentiates the antinociceptive effect of morphine in mice

Malekinejad

Taheri-Broujerdi

Moradi

et al. 2011

Phytotherapy Research

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Silymarin is a natural flavonoid found in the seeds of the milk thistle (Silybum marianum). Accumulating evidence indicates that silymarin exerts preventive/protective effects in animals and humans against many diseases. This study aimed to evaluate the antinociceptive effect of silymarin in the tail flick and writhing reaction assays. To understand the mechanism of the antinociceptive effect, the interaction of silymarin and morphine on acetic acid-induced reaction was examined. Moreover, the effect of naloxone as a narcotic receptor antagonist on silymarin-induced antinociception was studied. The antioxidant potency of silymarin was assessed by measuring the level of total thiol molecules in serum and the free radical scavenging activity. Silymarin lowered significantly (P < 0.05) the latency time in the tail flick test in a dose-dependent fashion. In the writhing reaction assay, silymarin dose- and time-dependently decreased the number of acetic acid-induced contractions. Silymarin also enhanced the morphine produced antinociceptive effect, while pretreatment with naloxone resulted in antagonism of the silymarin-induced antinociceptive effect, significantly (P < 0.05). Additionally, silymarin elevated the total thiol molecule level in the serum, which latter antioxidant property was confirmed by the concentration-dependent radical scavenging activity. The data suggest that the silymarin antinociceptive effect may be attributed to its interaction with the opioid system and its antioxidant capacity.

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Synergistic interaction between tramadol and dipyrone in thermal paw stimulation model in the rat

Rodrı́guez-Silverio

Arrieta

Flores‐Murrieta

2009

Drug Development Research

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Dipyrone, also known as metamizol, and tramadol are drugs that are widely used for the treatment of pain; however, side effects can limit their use. As dipyrone and tramadol produce side effects that are dose dependent, it seems appropriate to combine these drugs to reduce their dose requirements and, consequently, side effects. The purpose of this study was to evaluate whether dipyrone and tramadol produce antihyperalgesic effects in the thermal paw stimulation model in the rat, and whether there is a synergistic interaction between them. Using this model, dose-response curves were constructed for dipyrone (10-178 mg/kg, p.o.) and tramadol (1-32 mg/kg p.o.). From these curves, an ED 50 value was obtained and isobolographic analyses were carried out based on 1:1 and 0.6:0.4 (dipyrone:tramadol) potency ratio proportions. When the proportion was 1:1, an additive interaction was obtained, whereas the 0.6:0.4 proportion showed a synergistic interaction. These results suggest a good therapeutic potential of this combination. Drug Dev Res 70 : 450-454, 2009.

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The antinociceptive efficacy of morphine, metamizol, or their combination in an experimental rat model with different levels of inflammatory pain

Cited by 10 publications

References 31 publications

Pharmacological characteristics of metamizole

Pharmacological characteristics of metamizole

Silymarin potentiates the antinociceptive effect of morphine in mice

Synergistic interaction between tramadol and dipyrone in thermal paw stimulation model in the rat

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