Etorphine inhibition of pancreatic exocrine secretion in rats: Comparison with methadone

Chariot, J; Appia, F.; Vaille, C; Rozé, C

doi:10.1016/0014-2999(86)90394-8

Cited by 5 publications

(3 citation statements)

References 26 publications

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“…While the mechanisms remain unknown, these investigations have raised the possibility of a spinally medicated central effect, although a more direct endocrine effect on the pancreas cannot be ruled out. In this regard, it is interesting that in rats methadone inhibited pancreatic exocrine secretion in a naloxone-reversible manner (Chariot et al 1986). Thus, these observations emphasize the importance of opioids in endocrine actions and especially in glucose homeostasis.…”

Section: Introductionmentioning

confidence: 99%

Methadone-Induced Hypoglycemia

2013

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To determine if recent observations of hypoglycemia in patients receiving high dose methadone extended to an animal model, we explored the effects of methadone and other mu opioids on blood glucose levels in mice. Methadone lowered blood glucose in a dose-dependent manner with 20 mg/kg yielding a nadir in average glucose levels to 55 ± 6 mg/dL from a baseline of 172 ± 7 mg/dL, an effect that was antagonized by naloxone and mu selective antagonists β-funaltrexamine and naloxonazine. The effect was stereoselective and limited to only the l-isomer, while the d-isomer was ineffective. Despite the robust decrease in blood glucose produced by methadone, a series of other mu opioids, including morphine, fentanyl, levorphanol, oxycodone or morphine-6β-glucuronide failed to lower blood glucose levels. Similar differences among mu opioid agonists have been observed in other systems, suggesting the possible role of selected splice variants of the mu opioid receptor gene Oprm1. This mouse model recapitulates our clinical observations and emphasizes the need to carefully monitor glucose levels when using high methadone doses, particularly intravenously, and the need for controlled clinical trials.

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Section: Introductionmentioning

confidence: 99%

Methadone-Induced Hypoglycemia

2013

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“…25,26,27 Methadone's uniquely variable and relatively long half-life in comparison to other opioids may suggest a mechanism related to its constant effect on the HPA axis. Methadone displays antagonistic activity at the NMDA receptor and inhibits the reuptake of serotonin and norepinephrine in the central nervous system.…”

Section: Discussionmentioning

confidence: 99%

Methadone Use and the Risk of Hypoglycemia for Inpatients With Cancer Pain

Flory

Wiesenthal

Thaler

et al. 2016

Journal of Pain and Symptom Management

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Context Methadone is an important drug in the management of both cancer-related and non-cancer-related pain and is the main pharmacologic agent used in the treatment of opioid addiction. Unexpected hypoglycemia has been observed in patients receiving methadone, prompting a more detailed investigation. Objectives To evaluate the incidence of hypoglycemia in a cohort of inpatients receiving methadone versus other opioids including fentanyl, hydromorphone and morphine. Methods Retrospective observational cohort of inpatients in a tertiary cancer center admitted for more than 48 hours from November 1, 2011 to October 30, 2013. The main outcomes were lowest measured daily blood glucose (in mg/dl) and incidence of hypoglycemia (defined as blood glucose < 70 mg/dl, equivalent to 3.9 mmol/l) with variable methadone doses compared with other non-methadone opioids. Results Of the 641 eligible patients admitted during the study period who received at least one dose of methadone during admission, multivariable logistic regression showed significant associations between methadone and hypoglycemia at doses greater than 40 mg oral equivalents per day or with patient-controlled analgesia (PCA) use. A dose-response relationship was observed, with an odds ratio of 3.1 (95% confidence interval 2.5, 3.6) when doses greater than 80 mg/day were used. No evidence of increased risk of hypoglycemia or of a dose-response curve was seen for the other opioids. Conclusion The risk of hypoglycemia is increased for patients taking more than 40 mg oral methadone equivalents per day. When starting methadone at or above 40 mg a day, we recommend routine blood glucose monitoring.

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“…In anaesthetized rats, 2-deoxyglucose (ZDG) stimulates pancreatic secretion through a central effect involving activation of hypothalamic glucosensitive neurons projecting on motor neurons of the motor dorsal nucleus of the vagus. We have previously shown in this rat model that various opiates, including morphine, methadone, etorphine and other drugs, can potently depress 2DG-stimulated pancreatic secretion via central receptors (Vaille et al, 1975;RozC et al, 1978RozC et al, , 1982Chariot et al, 1986;Nagain et al, 1990Nagain et al, , 1992. whereas in the same model, chronic alcohol intake induces only faint inhibitory effects (Chariot, 1977(Chariot, , 1981RozC et al, 1979).…”

Section: Introductionmentioning

confidence: 92%

Modulation by alcohol and methadone of 2‐deoxyglucose‐stimulated pancreatic secretion in the rat

Nagain-Domaine

Tsocas

Presset

et al. 1996

Fundamemntal Clinical Pharma

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Alcohol intake is a major problem in drug addicts, and it is not clear whether the effects of alcohol and opiates are additive or potentiating. Vagally stimulated pancreatic secretion in rats is potently inhibited by opiates acting centrally at mu-receptors. In the present experiments, we determined the effects of methadone on 2-deoxyglucose (2DG)-stimulated pancreatic secretion in rats treated with acute (1.9 g/kg.3 h, intravenously) or chronic (1 or 3 month drinking) ethanol. In both acute and 1 month chronic alcoholic rats, methadone administered at its 50% inhibitory dose (ID50) reduced by about 50% 2DG-stimulated pancreatic secretion of sodium, bicarbonate and protein, and ethanol had only faint, nonsignificant inhibitory effects. In 3 month chronic alcoholic rats, similar results were obtained, but methadone inhibited 2DG-stimulated pancreatic secretion by 60 to 90% in these older rats. No significant interaction was found in any condition between ethanol and methadone, suggesting that they had only additive, but not potentiating effects in this method.

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Etorphine inhibition of pancreatic exocrine secretion in rats: Comparison with methadone

Cited by 5 publications

References 26 publications

Methadone-Induced Hypoglycemia

Methadone-Induced Hypoglycemia

Methadone Use and the Risk of Hypoglycemia for Inpatients With Cancer Pain

Modulation by alcohol and methadone of 2‐deoxyglucose‐stimulated pancreatic secretion in the rat

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