• Biomolecules & Therapeutics
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• v.7 no.1
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• pp.1-6
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• 1999

Effects of Panax ginseng on the morphine toxicity were studied in relation to its effects on the opioid receptor-G protein interactions. Morphine treatments (3 days) reduced the body weight increment rate and the weight of the thymus and spleen. These changes were usually recovered by the concomitant administration of ginseng total saponin (GTS) but occasionally further deteriorated. This discrepancy was studied in relation to the opioid receptor coupling to G protein, that is, the effects of morphine and GTS on the opioid receptors were studied using the antagonist-agonist competitive binding studies. When GTS recovered the morphine toxicity, morphine shifted the striatal $\delta$ receptors to slightly higher affinity state, and this was partly recovered by the GTS treatment. However, morphine did not have any effect on the affinity state of $\delta$ receptor from NG108-15 cells, suggesting that additional factors were needed for the modulation of the affinity states of $\delta$ receptor. Effects of morphine and GTS on $\mu$ receptor were complicate and variable, and we could not reach a clear conclusion. The morphine toxicity might accompany complicate biological involvements, and the modulation of the affinity states of the opioid receptors might explain a part of the effects of GTS on the morphine toxicity.

• Natural Product Sciences
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• v.13 no.1
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• pp.46-53
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• 2007

The effects of the alcoholic extract of Bacopa monniera (BMA) on morphine-induced pharmacological activities were studied in mice. Oral administration of the extract (40 mg/kg) significantly inhibited morphine-induced analgesic tolerance, withdrawal symptoms, hyperactivity, reverse tolerance, Dopamine receptor supersensitivity and apo-morphine-induced climbing behaviour in mice. The results of this study showed that, alcoholic extract of Bacopa monniera (BMA) exerted inhibitory effect against morphine-induced pharmacological effects, suggesting that the extract could be useful in the treatment of morphine toxicity.

• The Korean Journal of Physiology and Pharmacology
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• v.17 no.4
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• pp.347-357
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• 2013

Drug abuse has become a major social problem of the modern world and majority of these abusive drugs or their metabolites are excreted through the kidneys and, thus, the renal complications of these drugs are very common. Morphine, heroin, cocaine, nicotine and alcohol are the most commonly abused drugs, and their use is associated with various types of renal toxicity. The renal complications include a wide range of glomerular, interstitial and vascular diseases leading to acute or chronic renal failure. The present review discusses the renal toxicity profile and possible mechanisms of commonly abused drugs including morphine, heroin, cocaine, nicotine, caffeine and alcohol.

• Biomolecules & Therapeutics
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• v.3 no.3
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• pp.177-181
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• 1995

To investigate the possibility of Panax ginseng as a therapeutic agent for the immune suppression, ginseng total saponin (GTS) extracted from korean red ginseng was tested on immune functions from morphine-induced immune suppressed mice. To study how immune functions are affected by morphine and also to test whether GTS can be an useful therapeutic agent for morphine toxicity, several parameters were employed, body weight, immune organ weight, B cell functions, and T cell function. Morphine impaired the development of body weight and immune organ weight such as spleen and thymus. Morphine also depressed a B-cell function, antibody production. T-cell functions studied by type IV hypersensitivity test were most markedly affected by morphine treatment. GTS restored most of morphine-induced immune suppression. GTS restored the morphine-induced decrease in spleen weight to body weight ratio in a dose dependent manner, but not the body weight decrease. Also all of the morphine-induced impairments of B cell functions and cellmediated immunity were fully recovered by GTS. These results suggest that ginseng product could be very helpful for the treatment of immune suppression occurring in morphine abusers.

• The Korean Journal of Pain
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• v.4 no.1
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• pp.20-25
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• 1991

During the past decade the use of epidural opioids for treatment of chronic as well as postoperative pain has increased Epidural droperidol significantly reduced the side effects of epidural morphine without any appreciable toxicity, except possibly sedation. The purpose of this study was to assess the side effects and potentiation of analgesia of epidural morphine by dose-related droperidol. The results were as follows: 1) Duration of analgesia and pain score: There was no significant difference between morphine and dose-related droperidol groups. 2) Pruritus: Droperidol did not affect the incidence of pruritus with epidural morphine (P>0.05). 3) Nausea and vomiting: Significantly fewer patients experienced nausea and vomiting (16.7%) with droperidol 2.5mg(P<0.001). 4) Hypotensive episode Hypotension occurred in the groups with droperidol 1.25 mg (27. 8%) and 2.5mg(33.3%). 5) Sedation: It there was increased severity and incidence of sedation with dose related epidural droperidol. 6) Respiratory depression: There was no patient with respiratory depression in the morphine or droperidol group. 7) Extrapyramidal symptoms and others: There was no extrapyramidal symptom in the group with morphine and 0.25 mg droperidol, but 3 patients in the group with l.25 mg droperidol and 5 patients in the group with 2.5 mg droperidol how extrapyramidal symptoms. One patient in droperidol 2.5 mg developed suspicious NMS. It is suggested that the use of epidural droperidol to reduce the side effects of morphine may not be appropriate.

• Proceedings of the Ginseng society Conference
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• 2005.11a
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• pp.41-63
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• 2005

Ginseng has been useful for the treatment of diverse disease in oriental countries for thousands of years. In addition, a folk medicine prescribed by seven herbal drugs including Panax ginseng has been antinarcotics in the treatment of morphine-dependent patients. Many articles have been reported on these works. Therefore, we review the protective effects of Panax ginseng on the neurotoxicity induced by abuse drugs. Ginseng total saponins (GTS) extracted and isolated by Panax ginseng antagonized morphine-induced analgesia, and inhibited the development of analgesic tolerance to and physical dependence on morphine. CTS inhibited morphine-6 dehydrogenase, which catalyzes production of mophinone from morphine, and increased hepatic glutathione level responsible to toxicity. Therefore, wehypothesized that these dual actions of ginseng can be associated with the detoxication of morphine. In addition, the inhibitory or facilitated effects of GTS on electrically evoked contraction in guinea pig ileum (${\mu}$-receptors) and mouse vas deferens(${\delta}$-receptors) were not mediated through opioid receptors, suggesting non-opioid mechanisms. On the hand, antagonism of U-50,488H (${\kappa}$-agonist)-induced antinociception is mediated by serotonergic mechanisms. GTS also inhibited hyperactivity, reverse tolerance (sensitization) and conditioned place preference-induced by psychostimulants such as methamphetamine, cocaine and morphine. On the other hand, GTS reduced the dopamine levels induced by methamphetamine. Moreover, GTS blocked the development of dopamine receptor activation, showing antidopaminergic effect. We suggest that GTS prevent the methamphetamine-induced striatal dopaminergic neurotoxicity. In addition, Ginsenoside also attenuates morphine-induced CAMP signaling pathway. These results suggested that GTS might be useful for the therapy of the adverse actions of drugs with abuse liability.

• Archives of Pharmacal Research
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• v.28 no.9
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• pp.995-1001
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• 2005

Morphine-induced analgesia has been shown to be antagonized by ginseng total saponins (GTS), which also inhibit the development of analgesic tolerance to and physical dependence on morphine. GTS is involved in both of these processes by inhibiting morphine-6-dehydrogenase, which catalyzes the synthesis of morphinone from morphine, and by increasing the level of hepatic glutathione, which participates in the toxicity response. Thus, the dual actions of ginseng are associated with the detoxification of morphine. In addition, the inhibitory or facilitated effects of GTS on electrically evoked contractions in guinea pig ileum (I-L-receptors) and mouse vas deferens $(\delta-receptors)$ are not mediated through opioid receptors, suggesting the involvement of non-opioid mechanisms. GTS also attenuates hyperactivity, reverse tolerance (behavioral sensitization), and conditioned place preference induced by psychotropic agents, such as methamphetamine, cocaine, and morphine. These effects of GTS may be attributed to complex pharmacological actions between dopamine receptors and a serotonergic/adenosine $A_{2A}1\delta-opioid$ receptor complex. Ginsenosides also attenuate the morphine-induced cAMP signaling pathway. Together, the results suggest that GTS may be useful in the prevention and therapy of the behavioral side effects induced by psychotropic agents.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2005.11a
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• pp.49-66
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• 2005

Panax ginseng has been useful for the treatment of diverse disease in oriental countries for thousands of years. In addition, a folk medicine prescribed by seven herbal drugs including Panax ginseng has been antinarcotics in the treatment of morphine-dependent patients. Many articles have been reported on these works. Therefore, we review the protective effects of Panax ginseng on the neurotoxicity induced by abuse drugs. Ginseng total saponins (GTS) extracted and isolated by Panax ginseng antagonized Morphine-induced analgesia, and inhibited the development of analgesic tolerance to and physical dependence on morphine. GTS inhibited morphine-6 dehydrogenase, which catalyzes production of mophinone from morphine, and increased hepatic glutathione level responsible to toxicity. Therefore, we hypothesized that these dual actions of ginseng can be associated with the detoxication of morphine. In addition, the inhibitory or facilitated effects of GTS on electrically evoked contraction in guinea pig ileum ($\mu$-receptors) and mouse vas deferens($\delta$-receptors) were not mediated through opioid receptors, suggesting non-opioid mechanisms. On the hand, antagonism of U-50,488H ($\kappa$-agonist)-induced antinociception is mediated by serotonergic mechanisms. GTS also inhibited hyperactivity, reverse tolerance (sensitization) and conditioned place preference-induced by psychostimulants such as methamphetamine, cocaine and morphine. On the other hand, GTS reduced the dopamine levels induced by methamphetamine. Moreover, GTS blocked the development of dopamine receptor activation, showing antidopaminergic effect. We suggest that GTS Prevent the methamphetamine-induced striatal dopaminergic neurotoxicity. In addition, Ginsenoside also attenuates morphine-induced cAMP signaling pathway. These results suggested that GTS might be useful for the therapy of the adverse actions of drugs with abuse liability.

• The Korean Journal of Pain
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• v.12 no.1
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• pp.48-53
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• 1999

Background: Despite the popularity of epidural bupivacaine-morphine infusions for postoperative pain management, the optimum concentrations and dosages of bupivacaine have not been determined. At present, due to the disadvantages conferred by intense motor block and the increased risk of toxicity, many trials focus on reducing bupivacaine concentration and thus the evaluation of concentrations less than 0.1% may be warranted. Methods: Forty patients having epiduro-general anesthesia for hysterectomy were randomly assigned to one of two study groups. As a mean of postoperative pain control, all received 2 mg of epidural morphine bolusly 1 hr before the end of surgery and continuous epidural infusion was started using a two-day Infusor containing 4 mg of morphine in 100 ml of 0.125% bupivacaine (Group 0.125B, n=20) or 100 ml of 0.0625% bupivacaine (Group 0.0625B, n=20). Study endpoints included visual analog scales (VAS) for pain during rest and movement, sensory change and motor blockade. They were assessed at 2, 4, 8, 16, 24, 32, 40 and 48 hrs postoperatively. Results: For VAS during rest, no significance could be found between two groups over the course of study. But for VAS during movement, the 0.125B group showed more satisfactory results especially during early postoperative periods. For the incidence of complications, the 0.125B group revealed greater frequency of sensory change (25.0%) and motor blockade (10.0%) compared with the 0.0625B group. Conclusion: This study suggests that 0.0625% bupivacaine with morphine via epidural route was sufficient for pain control during rest but it was not satisfactory during movement especially in early postoperative periods. We also recommend that careful attention to motor blockade should be paid when using 0.125% bupivacaine.

• Toxicological Research
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• v.14 no.3
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• pp.427-433
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• 1998

The acute and genetic toxicity of DK1002 was subjected in this study. DK1002 which is a morphine-like new drug candidate synthesized by Dong-Kook Pharmaceutical Co. Ltd. is now under developing as a analgesics that have better drug efficacy and least addictive property. In acute toxicity study, the 50% lethal doses ($LD_{50}$) of DK1002 were determined as>2000mg/kg (p.o.), 237.0mg/kg(i.p.), 57.5mg/kg(i.v.), and 1266.9mg/kg (s.c.). And also, to study the genotoxicity of DK1002, we performed bacterial reversion assay with Salmonella typhimurium TA98, TA100, TA1535, and TA1537, and in vitro chromosomal aberration assay with Chinese hamster lung cells in the presence and absence of S-9 metabolic activation system. In vivo micronucleus assay using mouse bone marrow cells was also performed. From these results, DK1002 was revealed nonmutagenic potential in S. typhimurium TA98, TA100, TA1535, and TA537 both in the absence and presecne of metablic activation system. No clastogenicity of DK1002 was observed in chromosomal aberration assay in vitro as well as in micronucleus assay in vivo.