Interactions Between Metoclopramide and Morphine: Enhanced Antinociception and Motor Dysfunction in Rats

Kamerman, Peter R.; Becker, N; Fick, Linda G.

doi:10.1111/j.1440-1681.2007.04533.x

Cited by 8 publications

(7 citation statements)

References 60 publications

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“…Metoclopramide is suggested to potentiate morphine analgesia [19] through the interaction with opioid receptors [20] and other putative mechanisms [21]; nonetheless more recent experimental studies [22] and clinical data [23] do not support these hypotheses, which is in line with our results. However, it should be noted that conflicting results on morphine and metoclopramide analgesic interaction might be due to different dosing schedules and rat strains used in the aforementioned experimental studies.…”

Section: Discussionsupporting

confidence: 43%

Analgesic Effects of Morphine in Combination with Adjuvant Drugs in Rats

Leppert¹,

Okulicz-Kozaryn

Kamińska

et al. 2014

Pharmacology

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Background: Morphine is co-administered with adjuvant drugs to treat pain, nausea, vomiting, dyspnoea and delirium in cancer patients. Aim of the Study: To investigate analgesic effects of morphine when co-administered with adjuvant drugs. Material and Methods: Two-month-old male Wistar rats received single morphine doses alone (0.45 and 0.9 mg/kg) or with midazolam (0.3 mg/kg), haloperidol (0.15 and 0.45 mg/kg), levomepromazine (0.35 mg/kg), metoclopramide (1.0 mg/kg), and hyoscine butylbromide (1.7 mg/kg) as single subcutaneous injections. Analgesia was measured by the tail-flick test after 15, 30, 45, 60, and 90 min of drug administration. In the case of significant analgesia enhancement, analgesic and sedative effects were explored in 3-, 5-, 6-, 8-, and 11-month-old rats. Results: Significant morphine (0.9 mg/kg) analgesia enhancement was observed 60 min after haloperidol (0.15 and 0.45 mg/kg) and hyoscine butylbromide co-administration. The addition of haloperidol to morphine significantly increased analgesia in 6-, 8- and 11-month-old rats while in the case of hyoscine butylbromide co-administration this effect was observed only in 11-month-old rats. Conclusions: Haloperidol and hyoscine butylbromide enhanced morphine analgesia. Future studies may explore the repeated administration of these drug combinations in rats and humans. i 2014 S. Karger AG, Basel

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Section: Discussionsupporting

confidence: 43%

Analgesic Effects of Morphine in Combination with Adjuvant Drugs in Rats

Leppert¹,

Okulicz-Kozaryn

Kamińska

et al. 2014

Pharmacology

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“…Either drug alone is associated with side-effects, and it is unclear whether the combination alters the activity or the toxicity profile of either drug. The present study was conducted to evaluate potential interactions between morphine and metoclopramide, as has been suggested in some recent reports (Krenn et al 2000;Suchitra et al 2003;Kamerman et al 2007). Drug-drug interactions (DDI) can be caused by altered pharmacokinetics or altered pharmacodynamics (Pleuvry 2005;Leucuta and Vlase 2006).…”

Section: Discussionmentioning

confidence: 95%

“…One theory postulates an interaction between the two drugs via common central dopamine systems, but no direct mechanistic studies have been conducted to prove this. There are some reports of metoclopramide enhancing opioid-induced analgesia, and recent animal studies have reported such an interaction between metoclopramide and morphine (Suchitra et al 2003;Kamerman et al 2007). Whether metoclopramide alters the pharmacokinetics or pharmacodynamics of morphine is unknown.…”

Section: Introductionmentioning

confidence: 93%

“…Of these, M6G is an active metabolite. Morphine and metoclopramide are co-prescribed medications that have been reported to interact in a few studies, although the evidence has been indirect (Krenn et al 2000;Suchitra et al 2003;Kamerman et al 2007). One theory postulates an interaction between the two drugs via common central dopamine systems, but no direct mechanistic studies have been conducted to prove this.…”

Section: Introductionmentioning

confidence: 94%

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Lack of interaction between metoclopramide and morphinein vitroand in mice

et al. 2008

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1. This study examined interactions via common metabolism or via common pharmacodynamic pathways between frequently co-prescribed metoclopramide (a prokinetic) and morphine (an opioid analgesic). 2. In human liver microsomes, morphine 3-glucuronide and morphine 6-glucuronide formation had V(max) estimates of 6.2 +/- 0.07 and 0.75 +/- 0.01 (nmole min(-1) mg(-1) protein) and K(m) estimates of 1080 +/- 37 and 665 +/- 55 (microM), respectively. The in vitro K(i) for morphine 3-glucuronide formation in the presence of metoclopramide in human liver microsomes or recombinant uridine diphosphoglucuronosyltransferase 2B7 predicted a lack of in vivo interaction. 3. Morphine (2 mg kg(-1) subcutaneously) delayed gastrointestinal meal transit in mice, metoclopramide (10 mg kg(-1) subcutaneously) had no effect on meal transit, and metoclopramide did not alter this effect of morphine. 4. Morphine (2 or 5 mg kg(-1) subcutaneously) was antinociceptive in mice (hot plate test) and metoclopramide (10 mg kg(-1) subcutaneously) did not alter the antinociceptive effects of morphine. 5. Together, the data suggest a lack of interaction between morphine and metoclopramide.

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“…MID may also evoke hyperalgesia and its analgesic effects may be influenced by rats' races [32]. MET is suggested to potentiate opioid analgesia [33] through the interaction with opioid receptors [34] and other putative mechanisms [35], although experimental [36] and clinical data did not confirm these observations [37]. However, it should be noted that conflicting results on opioid and MET analgesic interaction might be due to different dosing schedules and rats races used in the aforementioned experimental studies.…”

Section: Research Wojciech Leppertmentioning

confidence: 56%

Analgesic and Anti–Inflammatory Effects of Oxycodone with Adjuvant Drugs in an Experimental Study of Nociceptive and Neuropathic Pain

Leppert¹,

Szulc²,

Kaczmarek³

et al. 2018

Neuropsychiatry

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Objective: Opioids are often combined with adjuvants to treat symptoms that accompany pain and with adjuvant analgesics to treat neuropathic pain. Herein, we aim to investigate the analgesic and anti-inflammatory effects of oxycodone and selected adjuvants in rats.Methods: Analgesic and anti-inflammatory effects of oxycodone were assessed after single subcutaneous (SC) (0.56 mg/kg) injections in rats, with the following drugs: midazolam (0.3 mg/kg), haloperidol (0.45 mg/kg), ketamine (0.3 mg/kg), hyoscine butylbromide (1.7 mg/kg), levomepromazine (0.35 mg/kg), and metoclopramide (1.0 mg/kg). Analgesia was assessed by the tail flick test. Anti-inflammatory activity was evaluated using a plethysmometer after carrageenan-induced edema. For neuropathic pain, analgesia was explored using the tail flick and von Frey tests. Neuropathic pain was induced by vincristine (0.1 mg/kg, i.p.) in male Wistar rats.Results: All tested combinations of oxycodone with particular adjuvants showed increased analgesia in comparison to oxycodone alone. Compared to oxycodone alone, combinations with midazolam, haloperidol, hyoscine butylbromide, and levomepromazine prolonged analgesia. Anti-inflammatory activities were observed after coadministration of oxycodone paired with haloperidol and ketamine, which is a new aspect of the pharmacological profile of oxycodone. In the neuropathic pain model, vincristine lowered pain threshold in rats and inhibited growth of normal rat body weight. Oxycodone in combination with adjuvant analgesics showed more potent analgesia than oxycodone alone, especially in the tail-flick test. In most cases, the maximum effects were observed for 15-30 min since combined SC administration.Conclusions: Analgesic and anti-inflammatory effects were observed in oxycodone combined with selected adjuvants in rats; although the mechanism of these interactions is not yet well understood. Further studies should test these combinations after chronic administration and assess the benefits and risks associated with the use of the tested combinations in humans.

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Interactions Between Metoclopramide and Morphine: Enhanced Antinociception and Motor Dysfunction in Rats

Cited by 8 publications

References 60 publications

Analgesic Effects of Morphine in Combination with Adjuvant Drugs in Rats

Analgesic Effects of Morphine in Combination with Adjuvant Drugs in Rats

Lack of interaction between metoclopramide and morphinein vitroand in mice

Analgesic and Anti–Inflammatory Effects of Oxycodone with Adjuvant Drugs in an Experimental Study of Nociceptive and Neuropathic Pain

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