A comparative study of the antipyretic effects of indomethacin and dipyrone in rats

Veiga-Souza, Fabiane H.; Cardoso, Rhanderson; Júnior, Mauro de Meló; Fabricio, Aline S C; Silva, V. M. S.; Lora, Maximilien; Brum‐Fernandes, Artur J. de; Rae, Giles A.; Ferreira, Sérgio Henrique; Zampronio, Aleksander Roberto

doi:10.1007/pl00000278

Cited by 59 publications

(62 citation statements)

References 45 publications

(68 reference statements)

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“…Similarly to NSAIDs, metamizole shows an evident antipyretic action, but the data concerning this mechanism are contradictory. Whereas some studies have reported that the antipyretic effect of dipyrone depends on inhibition of PGE 2 synthesis (Shimada et al 1994, Kanashiro et al 2009), others suggest that it does not (De Souza et al 2002, Pessini et al 2006, Malvar et al 2011. Recently, it has been demonstrated that 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 other COX inhibitors, which could be advantageous in treating fever (Malvar et al 2011).…”

Section: Pharmacological Characteristics Of Metamizolementioning

confidence: 99%

Pharmacological characteristics of metamizole

Jasiecka¹,

Maślanka²,

Jaroszewski³

2014

Polish Journal of Veterinary Sciences

113

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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: Pharmacological Characteristics Of Metamizolementioning

confidence: 99%

Pharmacological characteristics of metamizole

Jasiecka¹,

Maślanka²,

Jaroszewski³

2014

Polish Journal of Veterinary Sciences

113

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“…In fact, PGE 2 induces fever when injected centrally (13,33,38), and its levels in the cerebrospinal fluid (CSF) and in the POA rise in parallel with the generation of fever caused by several stimuli (9,12,16,19,23,27,35,42). Moreover, the inhibition of PG synthesis by cyclooxygenase (COX) inhibitors attenuates fever in humans and experimental animals, whereas these drugs do not affect fever induced by the administration of PGs (4,7,12,13,37,39). PGF 2␣ also induces fever when injected centrally (13,34), and its levels are increased in rat CSF in response to LPS (10).…”

mentioning

confidence: 99%

“…Moreover, the inhibition of PG synthesis by cyclooxygenase (COX) inhibitors attenuates fever in humans and experimental animals, whereas these drugs do not affect fever induced by the administration of PGs (4,7,12,13,37,39). PGF 2␣ also induces fever when injected centrally (13,34), and its levels are increased in rat CSF in response to LPS (10).…”

mentioning

confidence: 99%

“…Fever induced by intracerebroventricular injection of 100 fmol ET-1 in the rat is not modified by the pretreatment with a nonselective COX inhibitor, indomethacin, whereas the ET B receptor blockade does not affect fever induced by centrally administered IL-1␤ or TNF-␣ (15), whose pyrexic effects are effectively suppressed by indomethacin (13). Taken together, these findings led us to propose that, similar to corticotropin-releasing hormone, macrophage inflammatory protein-1, preformed pyrogenic factor, and IL-8 (13,31,46,47), ET-1 may act as a mediator of a putative COX-independent pathway of fever triggered by LPS in rats (15).…”

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confidence: 99%

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The effects of selective and nonselective cyclooxygenase inhibitors on endothelin-1-induced fever in rats

Fabricio

Veiga²,

Cristofoletti³

et al. 2005

American Journal of Physiology-Regulatory, Integrative and Comp

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It was previously shown that sustained fever can be induced in rats by central injection of endothelin-1 (ET-1). This peptide appears to participate in the mechanism(s) of LPS-induced fever, which is reduced by pretreatments with ET B receptor antagonists. In this study, we compared the effects of a nonselective cyclooxygenase (COX) inhibitor, indomethacin, with those of two selective COX-2 inhibitors, celecoxib and lumiracoxib, on ET-1-induced fever in rats. Fever induced in conscious animals by ET-1 (1 pmol icv) or LPS (5 g/kg iv) was prevented by pretreatments with celecoxib (5 and 10 mg/kg) or lumiracoxib (5 mg/kg) given by oral gavage 1 h before stimuli. Lower doses of celecoxib had partial (2.5 mg/kg) or no effect (1 mg/kg). Indomethacin (2 mg/kg ip) partially inhibited fever induced by LPS but had no effect on ET-1-induced fever. The levels of PGE2 and PGF2␣ in the cerebrospinal fluid (CSF) of pentobarbital sodium-anesthetized rats were significantly increased 3 h after the injection of LPS or ET-1. The latter increase was abolished by celecoxib at all tested doses and by indomethacin. In conclusion, selective COX-2 inhibitors were able to prevent ET-1-induced fever, indicating a role for COX-2 in this phenomenon. However, the fact that reduced CSF PG levels obtained with indomethacin and a low dose of celecoxib are not accompanied by changes in fever induced by ET-1, along with the lack of inhibitory effects of indomethacin on ET-1 fever, suggests that the latter might also involve COX-2-independent mechanisms.cyclooxygenase-2 inhibitors; indomethacin; prostaglandins; cerebrospinal fluid; lipopolysaccharide IT IS NOW WELL ESTABLISHED that the PGs represent the final mediators of fever induced by exogenous and endogenous pyrogens through an action on PG receptor-expressing neurons in the preoptic area (POA) of the anterior hypothalamus (33). In fact, PGE 2 induces fever when injected centrally (13,33,38), and its levels in the cerebrospinal fluid (CSF) and in the POA rise in parallel with the generation of fever caused by several stimuli (9,12,16,19,23,27,35,42). Moreover, the inhibition of PG synthesis by cyclooxygenase (COX) inhibitors attenuates fever in humans and experimental animals, whereas these drugs do not affect fever induced by the administration of PGs (4,7,12,13,37,39). PGF 2␣ also induces fever when injected centrally (13, 34), and its levels are increased in rat CSF in response to LPS (10).We have previously observed that endothelin-1 (ET-1), a member of the ET family of peptides (29), acts as a mediator of LPS-induced fever (15). In fact, intracerebroventricular (icv) pretreatment with the selective ET B receptor antagonist BQ-788 blunted fever induced by intravenous LPS or intracerebroventricular ET-1 (15). The rise in core temperature induced by intracerebroventricular ET-1 was accompanied by such thermoeffector response as cutaneous vasoconstriction, measured as a decrease in tail skin temperature (Fabricio, unpublished observation). The simultaneous occurrence of increased core temper...

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“…The gastric ulcer produced by indomethacin is due to the fact that this compound inhibits the synthesis of cytoprotective prostaglandins, synthesized by COX-1 and COX-2 in the stomach tissue 32 . Recently, it has been also shown that ROS possess an important role in the pathogenesis of mucosal damages caused by indomethacin, other agents besides the inhibition of COX enzymes 33 .…”

Section: Discussionmentioning

confidence: 99%

Untitled

2015

IJPSR

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Context:The leaves Morus alba have been traditionally used in Asian countries for treatment of different ailments. Objective: Present study was undertaken to evaluate the effect of ethanol extract from Morus alba leaves supplementation on gastric tissue glutathione level in indomethacin induced ulcers in rats. Materials and Methods: Ethanol extract from Morus alba leaves was administered at the doses 200 and 400 mg/kg/day, p.o. for seven days. Ulceration was induced by giving indomethacin. Ulcer index, gastric GSH level, gastric wall mucus level was estimated. The functioning of liver was also assayed. Results: The effects ethanol extract from Morus alba leaves were significant and comparable to reference treated group of rats. The gastric GSH levels were replenished by Morus alba leaves in 400 mg/kg. Conclusion: From this study it was concluded that ethanol extract from Morus alba leaves possess significant ulcer protection by replenishing gastric GSH and increasing gastric mucus level.

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A comparative study of the antipyretic effects of indomethacin and dipyrone in rats

Abstract: The antipyretic effect of dipyrone differs from that of indomethacin in that it does not depend on AVP release or inhibition of PG synthesis.

Cited by 59 publications

References 45 publications

Pharmacological characteristics of metamizole

Pharmacological characteristics of metamizole

The effects of selective and nonselective cyclooxygenase inhibitors on endothelin-1-induced fever in rats

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