Effects of naloxone and flumazenil on antinociceptive action of acetaminophen in rats

Madenoğlu, Halit; Kaçmaz, Mustafa; Aksu, Recep; Biçer, Cihangir; Yaba, Gülay; Yildiz, Karamehmet; Doğru, Kudret; Boyacı, Adem

doi:10.1016/j.curtheres.2010.03.001

Cited by 7 publications

(9 citation statements)

References 16 publications

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“…Interestingly, the combination of vitexin and acetaminophen showed clear infra-additive or antagonistic interaction. Recent evidence indicated that the antinociceptive action of acetaminophen is antagonized by flumazenil, a benzodiazepine sensitive GABA A receptor antagonist, which suggests GABA A receptors play an important role in acetaminophen-induced analgesia 45 . Our study also reveals the involvement of GABA A receptors in vitexin-induced analgesia.…”

Section: Discussionmentioning

confidence: 99%

Antinociceptive effects of vitexin in a mouse model of postoperative pain

Zhu

Mao

Liu

et al. 2016

Sci Rep

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Vitexin, a C-glycosylated flavone present in several medicinal herbs, has showed various pharmacological activities including antinociception. The present study investigated the antinociceptive effects of vitexin in a mouse model of postoperative pain. This model was prepared by making a surgical incision on the right hindpaw and von Frey filament test was used to assess mechanical hyperalgesia. Isobolographical analysis method was used to examine the interaction between vitexin and acetaminophen. A reliable mechanical hyperalgesia was observed at 2 h post-surgery and lasted for 4 days. Acute vitexin administration (3–10 mg/kg, i.p.) dose-dependently relieved this hyperalgesia, which was also observed from 1 to 3 days post-surgery during repeated daily treatment. However, repeated vitexin administration prior to surgery had no preventive value. The 10 mg/kg vitexin-induced antinociception was blocked by the opioid receptor antagonist naltrexone or the GABAA receptor antagonist bicuculline. The doses of vitexin used did not significantly suppress the locomotor activity. In addition, the combination of vitexin and acetaminophen produced an infra-additive effect in postoperative pain. Together, though vitexin-acetaminophen combination may not be useful for treating postoperative pain, vitexin exerts behaviorally-specific antinociception against postoperative pain mediated through opioid receptors and GABAA receptors, suggesting that vitexin may be useful for the control of postoperative pain.

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Section: Discussionmentioning

confidence: 99%

Antinociceptive effects of vitexin in a mouse model of postoperative pain

Zhu

Mao

Liu

et al. 2016

Sci Rep

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“…As a result, they found out that the enhancement in antinociceptive action made by 100 mg kg -1 acetaminophen was blocked by naloxone. In their study, Madenoglu et al (19) showed that opioid receptors were blocked with naloxone and then with acetaminophen which was administered at a dose of 300 mg kg -1 . Sawadogo et al (20) showed in a mouse study that 100 mg kg -1 administration of paracetamol had an analgesic effect.…”

Section: Discussionmentioning

confidence: 99%

The evaluation of effects of lornoxicam on blood flow and erythrocyte deformability in comparison with iv paracetamol in rats

Arslan

Fm²,

Işık³

et al. 2012

BLL

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Background: Lornoxicam and iv paracetamol are commonly preferred to be used for postoperative analgesia. Although Aspirin is a well known non-steroid anti-infl ammatory drug that decreases the erythrocyte deformability, there is no study comparing lornoxicam and iv paracetamol regarding their effects on erythrocyte deformability recorded in literature. The aim of this study was to compare the effects of lornoxicam and IV paracetamol on blood perfusion and erythrocyte deformability on rats. Methods: Twenty male Wistar Albino rats were randomly divided into three groups as Lornoxicam group (Group L), IV paracetamol group (Group P), and control group (Group C). Intraperitoneal administrations were done in all groups except Group C. Liver and renal blood fl ows were conducted by laser Doppler and euthanasia was performed via intraabdominal blood uptake. Erythrocyte deformability was measured using a constant fl ow fi ltrometer system. Results: Lornoxicam increased the relative resistance which shows the erythrocyte deformability in rats (p<0.05). The comparison of Groups C and P revealed no statistically different results (p=0.731) while Group L revealed statistically higher results than Group C (p=0.022). No statistically signifi cant differences were found between groups L and P (p=0.073). Liver and renal blood fl ow values in Group L were just numerically decreased not statistically whilst no statistically signifi cant difference was found between the three groups. Conclusions: Lornoxicam have lead to functional disorders related to tissue perfusion as a result of both decreased blood fl ow and erythrocyte deformability (Fig. 3, Ref. 21).

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“…Madenoglu et al (14) reported that fl umazenil antagonized the antinociceptive effect of acetaminophen in rats. However, this study proposed that fl umazenil caused an analgesic effect by using GABA receptors because the mechanism of action of paracetamol has not been fully understood.…”

Section: Discussionmentioning

confidence: 99%

“…Flumazenil, as a derivate of 1,4-imidazodiazepine, is an antagonist of benzodiazepines with partial agonist properties (13). In previous study, Flumazenil was shown to be able to antagonize the acetaminophen-related antinociceptive effect (14). These studies examined fl umazenil's potential benefi cial contribution to the reduction of APAP hepatotoxicity.…”

mentioning

confidence: 99%

The effect of different doses of flumazenil on acetaminophen toxicity in rats

Bozogluer

Madenoğlu²,

Aksu³

et al. 2012

BLL

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Abstract:Background: Acetaminophen is an analgesic drug that is used safely in therapeutic doses. At high doses, it causes hepatotoxicity, resulting in hepatic necrosis. Some medications and methods are available for treatment of acetaminophen overdose. However, results are inconsistent, and suffi cient outcomes cannot always be obtained. Objective: The mechanism of action of acetaminophen has not been fully understood. It has been suggested that it exerts its effects on GABA receptors. Flumazenil has been experimentally proven to produce an antagonism on acetaminophen's analgesic effect. The purpose of this study was to determine whether fl umazenil antagonized the toxic effects of acetaminophen overdose in rats. Methods: A total of 49 Wistar albino rats weighing between 250 -350 g were used in the study. Nine rats were examined for a preliminary study, and the other rats were randomly divided into fi ve groups with eight subjects in each. Control group: Saline; Acetaminophen group: 3 g/kg acetaminophen; Experimental Group F1: 3 g/kg acetaminophen + 0.1 mg/kg fl umazenil; Experimental group F2: 3 g/kg acetaminophen + 1 mg/kg fl umazenil; Experimental group F3: 3 g/kg acetaminophen + 10 mg/kg fl umazenil. Acetaminophen was administered in a 3 ml saline solution by way of gastric catheter. Flumazenil was administered by way of intraperitoneal injections. Serum levels of acetaminophen, AST, ALT, LDH, ALP and bilirubin were recorded over a 24-hour period. Results: Serum acetaminophen levels were similar between the groups. The AST, ALT, ALP, LDH, total bilirubin and direct bilirubin levels of Group A were signifi cantly higher compared with the Group C, Group F1, Group F2 and Group F3. There was not a statistically signifi cant difference in the AST, ALT, ALP, LDH, total bilirubin or direct bilirubin levels of the fl umazenil-administered groups. Conclusion: Flumazenil's prevention of the acetaminophen-induced increase in liver enzymes is promising. There is some indication that fl umazenil could be used in treatment of acetaminophen intoxication (Tab. 2, Ref. 25). Full Text in PDF www.elis.sk.

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Effects of naloxone and flumazenil on antinociceptive action of acetaminophen in rats

Abstract: Flumazenil antagonized the analgesic effect exerted by acetaminophen, while naloxone had no significant effect on acetaminophen's antinociceptive action in this pain model in rats.

Cited by 7 publications

References 16 publications

Antinociceptive effects of vitexin in a mouse model of postoperative pain

Antinociceptive effects of vitexin in a mouse model of postoperative pain

The evaluation of effects of lornoxicam on blood flow and erythrocyte deformability in comparison with iv paracetamol in rats

The effect of different doses of flumazenil on acetaminophen toxicity in rats

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