• Biomolecules & Therapeutics
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• v.2 no.4
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• pp.316-321
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• 1994

This study was undertaken to estimate whether nalbuphine, a mixed agonist/antagonist opioid analgesic produced psychic dependence. Moreover, the physical dependence liability of nalbuphine was compared with that of morphine after 7 days administrations of the drugs in mice and rats, and the effects of ginseng total saponin (GTS) on the development of physical dependence on nalbuphine were also studied. Nalbuphine did not produce psychic dependence. However, various abstinence signs precipitated by naloxone were observed in nalbuphine-dependent mice and rats. As the nature of the dependence syndrome produced by nalbuphine 30 mg/kg under these conditions seems similar to that induced by morphine 10 mg/kg, it is clear that nalbuphine possesses the substantial abuse potential. Therefore, nalbuphine may be needed to initiate more stringent controls for the prevention of nalbuphine abuse. On the other hand, GTS inhibited the development of physical dependence on nalbuphine and reduced the contents of dopamine and its metabolite in the brains of mice. Accordingly, results of this study suggest that the inhibitory effects of GTS on the development of physical dependence on nalbuphine may involve dopaminergic mechanism. GTS may be useful for the therapy of physical dependence on nalbuphine.

• Environmental Analysis Health and Toxicology
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• v.20 no.4 s.51
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• pp.343-350
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• 2005

In order to investigate the of effects of nalbuphine on immune system in mice, we examined the various immunological parameters. After single oral administration of nalbuphine (130, 260, 390 mg/kg, i.p.) to female ICR mite, the weights of bodies and organs (thymus, spleen, liver, kidney), and hematological parameters were examined on day 2, 4, 6, and 8. The increased rate of body weight, relative weight of organ, and hematological parameters in nalbuphine -treated groups, were not significantly changed when compared with control group. However, number of WBC was decreased by the treatment of nalbuphine. To assess the effects of nalbuphine on humoral immune responses, splenic IgM plaque forming cell (PFC) and serum IgM were assayed. When nalbuphine wat administered after immunization with SRBC, but not before immunization, splenic IgM PFC and ,serum IgM level against SRBC were significantly lowered in a dole -dependent manner. These results indicate that the suppressive effects of nalbuphine on primary humoral immune response may be dependent on the timing of its administration relative to the initial antigenic sensitization.

• The Korean Journal of Pain
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• v.11 no.2
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• pp.263-267
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• 1998

Background: This study was designed to know the dose requirement, analgesic efficacy and side effects of butorphanol and nalbuphine when administered with ketorolac by patient controlled analgesia (PCA) after total abdominal hysterectomy. Methods: Forty women who underwent total abdominal hysterectomy received ketorolac (bolus dose 2.4 mg, lockout interval 10 min) with either butorphanol (bolus dose 0.1 mg) or nalbuphine (bolus dose 1 mg) using PCA pump postoperatively. Results: Total amounts of 48 hr consumption were 8.7 mg (butorphanol)and 61.5 mg (nalbuphine). There were no significant differences between two groups in total ketorolac infusion doses, VAS score and side effects. Conclusions: Both butorphanol and nalbuphine were useful for PCA for postoperative pain control. We may suggest that ketorolac 180 mg with butorphanol 9 mg or nalbuphine 70 mg would be useful for 48 hr postoperative pain control.

• YAKHAK HOEJI
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• v.46 no.4
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• pp.276-282
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• 2002

Morphine has been used widely on the treatment of many types of chronic pain. However the development of tolerance to morphine by repeat application is a major problem in pain therapy. The purpose of the present study was to investigate whether combined administration of nalbuphine with morphine affects the development of tolerance to and dependence on morphine. We hypothesize that the use of nalbuphine, k-agonist may prove to be useful adjunct therapy to prevent morphine-induced undesirable effects in the management of some forms of chronic pain. Morphine (10 mg/kg) was injected to rats intraperitoneally for 5 days. The variable dose of nalbuphine (0.1, 1.0 and 5.0 mg/kg) was administered (i.p.) in combination with morphine injection. The development of tolerance to morphine was assessed by measuring the antinociceptive effect with the Randall-Selitto apparatus. The development of dependence on morphine was determined by the scoring the precipitated withdrawal signs for 20 min after injection of naloxone (10 mg/kg, i.p.). Nalbuphine did not attenuate antinociceptive effect of morphine in rats. Interestingly, combined administration of morphine with nalbuphine (100:1) significantly attenuated the development of morphine tolerance and dependence. These results suggest that the co-administration of nalbuphine with morphine in chronic morphine treatment can be one of therapies to reduce the development of dependence on morphine.

• The Korean Journal of Pain
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• v.5 no.2
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• pp.221-228
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• 1992

The effect of epidural nalbuphine on pruritus, nausea, vomiting, voiding difficulties and/or analgesia induced by epidural morphine was determined in sixty Cesarian delivery patients. They were physical status 1 or 2 by ASA classification and randomly divided into three groups. They were administered morphine 3 mg only(group A), nalbuphine 5 mg with morphine 3 mg(group B), or nalbuphine 10 mg with morphine 3 mg(group C) at the time of peritoneal closure. During postoperative 24 hours their analgesic effects were evaluated by visual analogue scale(0~10). Respiratory rates, Trieger dot test and severity of side effects(0~2) were also evaluated. The results were as follows; 1) Analgesic duration of the first epidural administration was significantly long in group A than other groups, but there was no difference between that of group B and group C. 2) Pruritus was more severe in group A than other groups but the severity was decreased by increasing nalbuphine dosage. 3) Nausea and or vomiting was mild in group C and the incidence of nausea and/or vomiting combined with pruritus was decreased by increasing nalbuphine dosage. 4) Voiding difficulties was more severe in group A than other groups but the severity was not decreased by increasing nalbuphine dosage. 5) None of the patients had objective sedation or low respiration rate(< 10 times/minute). We concluded that epidural administration of nalbuphine 10 mg with morphine 3mg for post-Cesarean section pain management is one of good methods to reduce side effects induced by epidural morphine.

• Archives of Pharmacal Research
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• v.29 no.8
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• pp.677-684
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• 2006

Morphine has been used widely on the treatment of many types of chronic pain. However the development of tolerance to and dependence on morphine by repeat application is a major problem in pain therapy. The purpose of the present study was to investigate whether combined administration of nalbuphine with morphine affects the development of tolerance to and dependence on morphine. We hypothesize that the use of nalbuphine, ${\kappa}-agonist$ may prove to be useful adjunct therapy to prevent morphine-induced undesirable effects in the management of some forms of chronic pain. Morphine (10 mg/kg) was injected to rats intraperitoneally for 5 day. The variable dose of nalbuphine (0.1, 1.0 and 5.0 mg/kg) was administered (i.p.) in combination with morphine injection. The development of morphine tolerance was assessed by measuring the antinociceptive effect with the Randall-Selitto apparatus. The development of dependence on morphine was determined by the scoring the precipitated withdrawal signs for 30 min after injection of naloxone (10 mg/kg, i.p.). Nalbuphine did not attenuate antinociceptive effect of morphine in rats. Interestingly, combined administration of morphine with nalbuphine (10:1) significantly attenuated the development of dependence on morphine. The elevation of $[^3H]MK-801$ binding in frontal cortex, dentate gyrus, and cerebellum after chronic morphine infusion was suppressed by the coadministration of nalbuphine. In addition, the elevation of NR1 expression by morphine was decreased by the coadministration of nalbuphine in rat cortex. These results suggest that the coadministration of nalbuphine with morphine in chronic pain treatment can be one of therapies to reduce the development of tolerance to and dependence on morphine.

• Journal of Ginseng Research
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• v.32 no.1
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• pp.1-7
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• 2008

Ginseng saponin has been shown to inhibit the development of dependence on morphine, cocaine, methamphetamine, but the antinarcotics effects of ginseng on nalbuphine remains still largely unknown. Ginseng administration attenuated the naloxone-induced jumping behavior on nalbuphine dependent mice. The development of morphine dependence was mediated through ${\mu}-opioid$ receptor, however, development of nalbuphine dependence was mediated through ${\kappa}-opioid$ receptor. However, it was found that the efficacy of analgesic antagonism of GTS was mediated through the serotonergic mechanism, not mediated through the opioid receptor. In addition, ginseng administration modulated cellular signal transduction in the brain. The increased NMDA receptor subunit (NR1, pNR1), phosphate extracellular signal regulated protein kinase (pERK), phosphate cAMP response element binding protein (pCREB) expression by nalbuphine was decreased by the administration of ginseng powder in cortex, hippocampus, striatum of rat brain. These results suggest that ginseng could be one of the targets of antinarcotic therapies to reduce the development of tolerance and dependence on nalbuphine as well as morphine.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1997.04a
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• pp.108-108
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• 1997

The effects of nalbuphine.HCI on the spontaneous locomotor activity and primary humoral immune response were investigated in ICR mice. Nalbuphine was intraperitoneally administered with the dose of 130, 260, 360 mg/kg in mice. The locomotor activity such as distance traveled was observed for 90min at 10min intervals. Nalbuphine showed the biphasic dose-response relationship on the spontaneous locomotor activity. IgM plaque forming cells(PFC) in splenocytes and IgM level in antiserum were significantly decreased depending on the dose of nalbuphine when nalbuphine was administered after the immunization, but slightly increased only at the low dose in the case of nabuphine administration after the immunization(SRBC).

• The Korean Journal of Pain
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• v.3 no.1
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• pp.44-50
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• 1990

Epidural injection of narcotics for postoperative pain relief has been well reported. Caudal nalbuphine was assessed as a postoperative analgesic in a randomized double blind study of 80 patients after perianal surgery. Caudal block was carried out with 1.5% lidocaine 25 ml (Group 1) in 20 patients, and mixed with nalbuphine 3 mg (Group 2) in 20 patients, nalbuphine 5 mg (Group 3) in 20 patients, and nalbuphine 10 mg (Group 4) in 20 patients. Pain relief was evaluated by the subsquent need for systemic analgesics (Pethidine). In group 4, the use of systemic analgesics was significantly reduced for the first 24 hours postoperatively. Urinary retention was not correlated with nalbuphin dose.

• The Korean Journal of Pain
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• v.6 no.1
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• pp.60-66
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• 1993

The clinical effects of epidural nalbuphine were compared to those of epidural morphine in sixty Cesarean delivery. They were physical status 1 or 2 by ASA classification and randomly divided into three groups. They were administered nalbuphine 5 mg(Group N5), nalbuphine 10 mg(Group N10) or morphine 3 mg(Group M3) through an indwelling epidural catheter at the time of peritoneal closure. During the first postoperative 24 hours, their analgesic effects were evaluated by visual analogue scale(0-10), respiration rates and Trieger dot test. The severity of side effects(0-2) was also evaluated. The results were as follows ; 1) The number of patients who needed additional epidural analgesics was least in group M3 (p<0.05). There was no significant difference between group N5 and group N10. 2) The duration between the first and second epidural administration was ; 19.2 hours in group M3, 8.6 hours in group N10 and 5.4 hours in group N5. There was a significant difference each group (p<0.05). 3) From the fourth post operative hour, both groups receiving nalbuphine showed a higher VAS score compared to group M3(p<0.05). 4) The incidence of pruritus, nausea, vomiting and voiding difficulty were more severe in group M3 compared with the other groups. However the severity did not increase with increasing nalbuphine dosage. 5) There were no patients showing objective sedation or low respiration rate(10 times/minute). We concluded that epidural administration of nalbuphine 5 mg or 10 mg is one way of post operative pain control. Its side effects were less than epidural morphine, but it is a less convenient in the method of analgesia.