The Effect of Paracetamol and Tropisetron on Pain: Experimental Studies and a Review of Published Data

Tiippana, Elina; Hamunen, Katri; Kontinen, Vesa K.; Kalso, Eija

doi:10.1111/j.1742-7843.2012.00935.x

Cited by 24 publications

(16 citation statements)

References 47 publications

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“…Regarding the potential target sites, it has been indicated that the synergism of nefopam and acetaminophen may occurs in connection with the descending serotonergic (5-HT) pathways and spinal serotonin 5-HT receptors. It has been reported that the potential effect of acetaminophen is indirectly/directly related to 5-HT 3 receptors at spinal sites (50,51) and descending serotonergic pathways (52). Similarly, the action of nefopam have been indicated to involve serotonergic pathways and 5-HT receptors (49,53).…”

Section: Discussionmentioning

confidence: 99%

Enhanced analgesic effects of nefopam in combination with acetaminophen in rodents

Zhuang

et al. 2017

biom rep

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Abstract. Nefopam, an analgesic drug, effectively elicits antinociception in the majority of noxious and thermal models in rodents. Acetaminophen is among the most commonly used analgesic and antipyretic drugs worldwide, either on prescription or over the counter. The present study aimed to investigate the analgesic activity of nefopam combined with acetaminophen, which was expected to maximize the potency of analgesia and decrease the dose of nefopam required. Three series of experiments, namely acetic acid-induced writhing tests in mice, hot plate tests in mice and tail flick tests in rats, were used to evaluate the analgesic effect. Initially, an optimum proportion of the two drugs, 3.5 mg/kg nefopam (N) + 60 mg/kg acetaminophen (A), was determined by orthogonal array design based on writhing response number. Subsequently, combinations of N and A (1.75 N + 30 A, 3.5 N + 60 A and 7.0 N + 120 A mg/kg) were determined to elicit antinociception in the writhing test (P<0.01 vs. normal saline control) in a dose-dependent manner. In the hot plate test, hot plate latencies up to 60 min after drug treatment were observed. The combination of 7.0 N + 120 A mg/kg exerted a greater cumulative antinociceptive effect throughout the observation period, with an area under the curve value of 1,156.95±199.30 area units (AU), compared with that achieved by 7.0 N mg/kg alone (632.12±62.38 AU). Furthermore, both monotherapy and compound therapy exhibited antinociception dose-dependently in the tail-flick test. However, a combination of 5.0 N + 84 A mg/kg exerted greater analgesic effect compared with 5.0 N mg/kg alone. The data obtained demonstrate that acetaminophen may enhance the antinociceptive activity of nefopam. Thus, coadministration of nefopam with acetaminophen warrants clinical evaluation.

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Section: Discussionmentioning

confidence: 99%

Enhanced analgesic effects of nefopam in combination with acetaminophen in rodents

Zhuang

et al. 2017

biom rep

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“…It has been shown that acetaminophen intake for 3 days reduces the urinary excretion of PGE2 by 30% in elderly and patients with impaired renal function [25]. Other mechanisms of action of acetaminophen at a molecular level have been proposed as the production of reactive metabolites by the peroxidase function of COX-2 or interaction with serotonin receptors 5-HT3 [26,27]. The similarity in changes in cystatin C and creatinine values throughout the study in patients treated with dipyrone and acetaminophen supports the idea that dipyrone used for short periods of time might be safe in these patients.…”

Section: Discussionmentioning

confidence: 99%

Acute Effects of Dipyrone on Renal Function in Patients with Cirrhosis: A Randomized Controlled Trial

Zapater

Llanos

Barquero

et al. 2014

Basic Clin Pharma Tox

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Use of non-steroidal anti-inflammatory drugs in cirrhosis has been associated with impairment of renal function based on its ability to inhibit the renal production of prostaglandins. Renal effects of dipyrone in patients with cirrhosis have not been evaluated. We aimed to assess the renal effect of therapeutic doses of dipyrone used for short periods of time in patients with cirrhosis. Twenty-nine patients with cirrhosis were included in an observer-blind clinical trial. Patients were randomized to receive three times a day oral acetaminophen (500 mg; N = 15) or dipyrone (575 mg; N = 14) for 72 hr. Serum and urine samples were obtained at baseline, 48 and 72 hr, and cystatin C, creatinine, aldosterone, 6-keto-Prostaglandin-F1 alpha and prostaglandin E2 were measured. Cystatin C and creatinine levels remained comparable in patients treated with acetaminophen and dipyrone. Urine and serum prostaglandins concentrations were significantly decreased at 72 hr in patients treated with dipyrone regardless of the status of ascites. One patient with ascites treated with dipyrone required a paracentesis and developed renal insufficiency. We conclude that dipyrone and acetaminophen did not reduce renal function when used for short periods of time (up to 72 hr) in patients with cirrhosis. However, considering that dipyrone lowered renal vasodilator prostaglandins synthesis, acetaminophen appears as the safest choice with respect to kidney function in cirrhosis.Patients with advanced cirrhosis show a hyperdynamic circulation, characterized by an enhanced splanchnic blood flow, arterial vasodilatation and hypervolaemia, together with an increased reabsorption of sodium and water related with a marked activation of neurohormonal vasoconstrictor systems such as the sympathetic nervous and renin-angiotensin systems [1,2]. In fact, angiotensin II reduces renal blood flow and renal excretory function by directly constricting the renal vascular smooth muscle and by facilitating renal sympathetic tone. This detrimental effect can partly be counteracted by renal prostaglandin production through their local vasodilating effects [2,3].Patients with cirrhosis show an increased production of prostaglandin E2 (PGE2) in the medullary and juxtamedullary vessels of kidney that has been associated with relative

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“…Controversial data have been observed between the results in healthy volunteers and patients with pain. 16 The findings of these studies will be discussed in the following sections.…”

Section: The Role Of the Central Serotonergic System In Acetaminophenmentioning

confidence: 98%

The Contribution of Serotonergic Receptors and Nitric Oxide Systems in the Analgesic Effect of Acetaminophen: An Overview of the Last Decade

Hamurtekin

Nouilati

Demirbatir

et al. 2020

tjps

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Yeşim HAMURTEKİN, Ammar NOUILATI, Cansu DEMİRBATIR, Emre HAMURTEKİN* Asetaminofen yaygın kullanılan analjezik ve antipiretik bir ajandır. Reçetesiz verilebilen formülasyonlarının da mevcudiyeti sık kullanımını artırmıştır. Günümüze kadar asetaminofenin analjezik etki mekanizmasını inceleyen bir çok çalışma bulunmaktadır. Santral sinir sisteminde siklooksijenaz yolağını inhibe etmesinin yanında, opioiderjik, kannabinoiderjik, dopaminerjik, kolinerjik ve nitrerjik sistemler kadar, bulbospinal serotonerjik yolaklar gibi analjezik etkili inen inhibitör yolakların da asetaminofenin analjezik etkisinde katkısı olan olası mekanizmalar olduğu önerilmiştir. Bu derlemede santral serotonerjik sistem ve santral sinir sistemindeki serotonerjik reseptör alt tiplerinin parasetamolün analjezik etkisine katkısını ortaya koyan verileri bir araya getirmeyi amaçladık. Bunu yaparken, esas olarak son on yılda yapılmış çalışmalara odaklandık ve önceki verilerle son eklenenler arasında bir bağlantı kurmaya çalıştık. Serotonerjik sistemin katkısına ek olarak, aynı zamanda son on yıldaki yeni bulgularla asetaminofenin ağrı kesici etkisinde nitrik oksidin rolünü de derledik. Anahtar kelimeler: Asetaminofen, serotonin, ağrı, nitrik oksit Acetaminophen is a widely used analgesic and antipyretic agent. It is also available in over the counter formulations, which has increased its wide use. There have been many studies to date that have aimed to evaluate the mechanism of the analgesic action of acetaminophen. Additional to the inhibition of the cyclooxygenase pathway in the central nervous system, the involvement of opioidergic, cannabinoidergic, dopaminergic, cholinergic, and nitrergic systems as well as the contribution of descending pain inhibitory systems like the bulbospinal serotonergic pathway has been proposed as possible mechanisms of the analgesic action of acetaminophen. In this review, we aimed to collect the data from studies revealing the contribution of the central serotonergic system and the role of central nervous system-located serotonergic receptor subtypes in the analgesic effect of acetaminophen. While doing this, we mainly focused on the research that has been performed in the last ten years and tried to link the previous data with the lately added results. In addition to serotonergic system involvement, we also reviewed the role of nitric oxide in the analgesic action of acetaminophen, especially with the new findings reported over the last decade.

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The Effect of Paracetamol and Tropisetron on Pain: Experimental Studies and a Review of Published Data

Cited by 24 publications

References 47 publications

Enhanced analgesic effects of nefopam in combination with acetaminophen in rodents

Enhanced analgesic effects of nefopam in combination with acetaminophen in rodents

Acute Effects of Dipyrone on Renal Function in Patients with Cirrhosis: A Randomized Controlled Trial

The Contribution of Serotonergic Receptors and Nitric Oxide Systems in the Analgesic Effect of Acetaminophen: An Overview of the Last Decade

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