Synergistic interaction between butorphanol and dexmedetomidine in antinociception

Ahsan, Muhammad Zaeem; Khan, Farhan Ullah; Zhao, Min; Wang, Yongxiang

doi:10.1016/j.ejps.2020.105322

Cited by 13 publications

(9 citation statements)

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“…Previous studies have shown that the combination of midazolam and butorphanol after IN administration produced a better sedative effect in cockatiels ( Nymphicus hollandicus ) than IN midazolam alone [ 6 ], and a combination of midazolam and DXM after IN administration caused a more obvious sedative effect than IN midazolam alone in pigeons ( Columba livia ) [ 7 ]. In mice, the combination of butorphanol and DXM could produce better sedation and antinociception resulting from synergistic interaction between the opioid and alpha2 receptors [ 21 ]. No studies are available on the effect of IN burorphanol or DXM or a combination of DXM and butorphanol in birds.…”

Section: Discussionmentioning

confidence: 99%

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Pharmacokinetics and Pharmacodynamics of Butorphanol and Dexmedetomidine after Intranasal Administration in Broiler Chickens (Gallus gallus domesticus)

Sha

Kongara

Singh

et al. 2022

Veterinary Sciences

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Butorphanol and dexmedetomidine (DXM) can produce analgesia in birds. Intranasal (IN) route of drug administration is easier, and free of risks such as pain and tissue damage compared with intravenous, intramuscular or subcutaneous routes in bird species, including wild birds. Although previous studies have demonstrated the use of IN route for producing sedation, no studies are available on the pharmacokinetics and pharmacodynamics of IN drugs in birds. This study analyzed the pharmacokinetics and sedative–analgesic efficacy of intranasal butorphanol (2 mg/kg), dexmedetomidine (80 µg/kg) and their combination (butorphanol, 2 mg/kg; DXM, 80 µg/kg) in healthy, male, Ross broiler chickens (n = 6/group) aged between 6 and 8 weeks. Maximum plasma concentration (Cmax, p = 0.01), area under the plasma concentration-time curve from time zero to 120 min (AUC0 to 120, p = 0.02) and apparent volume of distribution at steady state (Vss, p = 0.02) of DXM were significantly higher than that of DXM co-administered with butorphanol. The mechanical nociceptive thresholds and the sedation scores of DXM group were significantly higher than the baseline value. Dexmedetomidine (80 µg/kg, IN) was effective in chickens, and the drug absorption was more rapid than that of DXM with butorphanol. However, the duration of action of DXM was short. Lower value of Cmax and nociceptive thresholds showed the nonsignificant efficacy of butorphanol at a dose of 2 mg/kg after IN administration in broiler chickens.

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Section: Discussionmentioning

confidence: 99%

“…Both butorphanol and DXM are metabolized in mammals by hepatic hydroxylation and glucuronidation [ 24 , 25 ], and a study has reported synergism in their effect in mice [ 21 ]. There are no reports of pharmacokinetic interactions of butorphanol and DXM in any avian species.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics and Pharmacodynamics of Butorphanol and Dexmedetomidine after Intranasal Administration in Broiler Chickens (Gallus gallus domesticus)

Sha

Kongara

Singh

et al. 2022

Veterinary Sciences

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“…In addition, butorphanol is widely used in postoperative patient-controlled intravenous analgesia (PCIA), but it can cause many side effects when used alone ( 13 ). However, clinical studies suggest that dexmedetomidine can enhance the analgesic effect of butorphanol, and its combination can reduce its adverse effects ( 14 , 15 ). In the present study, we designed to study the analgesic and sedative effect of different doses of dexmedetomidine combined with butorphanol in continuous analgesia after a cesarean section.…”

Section: Introductionmentioning

confidence: 99%

Analgesic and Sedative Effects of Different Doses of Dexmedetomidine Combined with Butorphanol in Continuous Analgesia after a Cesarean Section

Liu

Wang

et al. 2022

Front. Surg.

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ObjectiveThe present study is designed to study the analgesic and sedative effect of different doses of dexmedetomidine combined with butorphanol in continuous analgesia after a cesarean section.MethodsA total of 60 puerperae undergoing a cesarean section recruited from a single center were divided into three groups according to the postoperative continuous analgesia protocol: control group (100 mL of normal saline containing 10 µg/kg fentanyl and 0.25 mg of palonosetron, 2 mL/h for continuous analgesia for 48 h), DB1 group (100 mL of normal saline containing 1.0 µg/kg dexmedetomidine, 4 mg of butorphanol, 10 µg/kg fentanyl, and 0.25 mg of palonosetron, 2 mL/h for continuous analgesia for 48 h), and DB2 group (100 mL normal saline containing 2.0 µg/kg dexmedetomidine, 4 mg of butorphanol, 10 µg/kg fentanyl, and 0.25 mg of palonosetron, 2 mL/h for continuous analgesia for 48 h). We compared the blood pressure, heart rate, oxygen saturation, VAS score, Ramsay score, and adverse reactions of puerperae among the three groups after surgery.ResultsThe baseline data all have no significant difference in the three groups (p > 0.05). Compared with those in the control group, the systolic blood pressure, diastolic blood pressure, heart rate, and VAS score of the puerperae in the DB1 group and DB2 group were significantly decreased at 6, 24, and 48 h (P < 0.05), while the Ramsay scores of the puerperae in DB1 group and DB2 group were significantly increased at 6, 24, and 48 h (p < 0.05). At the same time, the systolic blood pressure, diastolic blood pressure, heart rate, and VAS score of the puerperae in the DB2 group were significantly lower than those in the DB1 group (P < 0.05), while the Ramsay scores of the puerperae in DB2 group were significantly higher than those in the DB1 group (P < 0.05). Also, there is no significant difference in oxygen saturation and adverse reactions of puerperae among the three groups after surgery (p > 0.05).ConclusionDexmedetomidine combined with butorphanol can improve the analgesic and sedative effects in continuous analgesia after a cesarean section, and the analgesic and sedative effects of dexmedetomidine in the high-dose group are better than those in the low-dose group.

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“…They have cardioprotective effects on ischemic heart disease (Tanaka et al, 2014). Butorphanol is a synthetic opioid, which is used for the treatment of chronic pain (Ahsan et al, 2020; Gress et al, 2020). Butorphanol exerts the pulmonary protective, anti‐inflammatory, and antitumor activities (Meng et al, 2019; Wang, Li, et al, 2020; Wang, Zeng, et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Multiple pathways are responsible to the inhibitory effect of butorphanol on OGD/R‐induced apoptosis in AC16 cardiomyocytes

Wu¹,

Liu²,

Tu³

et al. 2021

J of Applied Toxicology

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Ischemic heart disease is the leading cause of cardiovascular mortality, which is related to cardiac myocyte apoptosis. Butorphanol is an opioid receptor agonist with potential cardioprotective function. The purpose of this work is to explore the function and mechanism of butorphanol in oxygen and glucose deprivation/reperfusion (OGD/R)‐induced cardiomyocyte apoptosis. The overlapping targets of ischemic heart disease and butorphanol were analyzed according to GeneCards, ParmMapper, Cytoscape, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Human cardiomyocyte AC16 cells were incubated with butorphanol and then stimulated with OGD/R. Cell injury was investigated by Cell Counting Kit‐8, lactate dehydrogenase (LDH) assay kit, TUNEL staining, caspase‐3 activity assay kit, and Western blotting. The proteins in signaling pathways were measured using Western blotting. A total of 93 overlapping targets of ischemic heart disease and butorphanol were obtained. Pathway analysis exhibited that these targets might be involved in multiple signaling pathways. Butorphanol alone showed little cytotoxicity to cardiomyocytes, and it protected against OGD/R‐induced viability inhibition, LDH release, cell apoptosis, and increase of caspase‐3 activity and expression levels of cleaved caspase‐3 and Bim. Butorphanol promoted the activation of the phosphoinositide 3‐kinase (PI3K)/protein kinase B (Akt)/forkhead box O (FoxO) and hypoxia‐inducible factor‐1α (HIF‐1α)/vascular endothelial growth factor (VEGF) pathways and attenuated the activation of the mitogen‐activated protein kinase (MAPK) signaling in OGD/R‐treated cardiomyocytes. In conclusion, butorphanol prevents OGD/R‐induced cardiomyocyte apoptosis through activating the PI3K/Akt/FoxO and HIF‐1α/VEGF pathways and inactivating the MAPK pathway.

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Synergistic interaction between butorphanol and dexmedetomidine in antinociception

Cited by 13 publications

References 50 publications

Pharmacokinetics and Pharmacodynamics of Butorphanol and Dexmedetomidine after Intranasal Administration in Broiler Chickens (Gallus gallus domesticus)

Pharmacokinetics and Pharmacodynamics of Butorphanol and Dexmedetomidine after Intranasal Administration in Broiler Chickens (Gallus gallus domesticus)

Analgesic and Sedative Effects of Different Doses of Dexmedetomidine Combined with Butorphanol in Continuous Analgesia after a Cesarean Section

Multiple pathways are responsible to the inhibitory effect of butorphanol on OGD/R‐induced apoptosis in AC16 cardiomyocytes

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