• Title, Summary, Keyword: morphine

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Effects of Morphine on the Transmembrane Potential and the Short Circuit Current of Frog Skin (개구리 피부(皮腐)의 막전위(膜電位) 및 단락전류(短絡電流)에 미치는 Morphine의 영향)

  • Chae Soo-Wan;Cho Kyu-Park
    • The Korean Journal of Pharmacology
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    • v.20 no.1
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    • pp.23-32
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    • 1984
  • The effects of morphine on the transmembrane potential and the short circuit current in the isolated frog skin were studied under different experimental conditions. The measurem ents of the transmembrane potential and the short circuit current were carried out according to Ussing and Zerahn's method. Experimental results were summerized as follows: 1) $5{\pm}10^{-3}$M of morphine markedly depressed the transmembrane potential and the short circuit current of the naive preparation. The peak of these inhibitory effects of morphine was observed about 1 hour after administration of the drug. 2) However $10^{-4}$M of naloxone did not affect these effects of morphine. 3) Decrease of $K^+$, increase of $K^+$ or $Ca^{2+}$ in the perfusate, markedly potentiated the inhibitory action of morphine on both transmembrane potential and short circuit current of the frog skin, and addition of $Mn^{2+}$ to the solution depressed the effect of morphine on the transmembrane potential, while the inhibitory effect of morphine on the short circuit current was diminished in the $Ca^{2+}$-free ringer solution, and increase of $Mg^{2+}$ concentration depressed those effect of morphine on both electrical parameters. 4) In the morphine treated preparations, transmembrane potential and short circuit current were decreased in the early phase of drug treatment ($1{\sim}2$ days), but gradually increased to the significantly high level from the control (48 days after treatment). In these preparations, the effects of morphine on both electrical parameters were also potentiated in the early phase, but markedly diminished in the late phase of treatment. From the above results, it is postulated that the pharmacological actions of morphine as well as development of the tolerance by morphine may be partially related to the changes of ion fluxes and/or permeabilities of skin by the drug.

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Effects of Ginseng Saponins on Morphine 6-Dehydrogenase

  • Kim, Hack-Seang;Jeong, In-Sook
    • Korean Journal of Pharmacognosy
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    • v.25 no.2
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    • pp.160-166
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    • 1994
  • The possible mechanisms of ginseng saponins on the inhibition of the development of morphine tolerance and physical dependence were investigated in the aspects of morphine metabolism by morphine 6-dehydrogenase. The administration of morphine causes a reduction of non-protein sulfhydryl contents in the liver, because morphinone metabolized from morphine by morphine 6-dehydrogenase conjugates with sulfhydryl compounds. However, ginseng saponins inhibited the activity of morphine 6-dehydrogenase which catalyzed the production of morphinone from morphine. In addition, ginseng saponins inhibited the reduction of non-protein sulfhydryl levels by increasing the level of hepatic glutathione. These results suggest that the dual action of the above plays an important role in the inhibition of the development of morphine tolerance and physical dependence. On the other hand, it was observed that less polar components of ginseng saponins with parent structures were more active components in vitro.

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Supraspinal Nitric Oxide Synthesis Inhibition Enhanced Antinociception of Morphine in Morphine Tolerant Rats (모르핀내성시 뇌실내 NO 합성억제제 투여가 모르핀의 진통효과에 미치는 형향)

  • Song, Ho-Kyung;Jang, Yeon
    • The Korean Journal of Pain
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    • v.14 no.2
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    • pp.225-230
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    • 2001
  • Background: Opioids such as morphine are widely used in the treatment for pain, but chronic treatment with morphine can be complicated by the development of tolerance. The mechnisms of tolerance were still not completely understood, but recently it has been reported that NOS inhibitors can prevent development of morphine tolerance in animals. The present study accessed the possible role of supraspinal NO on antinociceptive effect of morphine in morphine tolerance using a highly specific inhibitor of the neuronal isoform of NOS, 1-(2-trifluoromethylphenyl) imidazole (TRIM). Methods: Thirty two male SD rats (300 g) were prepared with intracerebroventricular (icv) and IV cannulae. We administrated IV morphine, 3 mg/kg, daily for 4 days, resulting in tolerance. On the fifth day, a challenge dose of morphine, 3 mg/kg, was administered following pretreatment with icv TRIM, $10{\mu}g$. We also evaluated the antinociceptive effect of icv TRIM alone and the effect on a single dose of morphine (3 mg/kg) in morphine nave rats. Antinociception from morphine was determined by response to intraplantar injection of 5% formalin $100{\mu}l$ was qualified as the number of flinches in the first 0-10 min (first phase), 10-40 min Phase IIa, and 40-60 min (Phase IIb). Results: Pretreatment with icv TRIM significantly enhanced the antinociceptive effects of systemically administered morphine in morphine tolerant rats. The antinociceptive effect of morphine in opioid nave rats was also significantly increased by pretreatment with icv TRIM. Conclusions: Our results further support the hypothesis that supraspinal NO modulates morphine-sensitive nociceptive process in morphine tolerance due to chronic intravenous administration.

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The Development of Tolerance to and Dependence on Morphine are Reduced by Co-administration of Nalbuphine in Rat (Nalbuphine의 병용투여에 의한 morphine의 내성 및 의존성 형성 저하효과)

  • 정면우;임화경;전용준;김혜정;박인숙;오우용;왕소영;박윤주;강주희
    • 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.

Attenuation of Morphine Tolerance and Withdrawal Syndrome by Coadministration of Nalbuphine

  • Jang, So-Yong;Kim, Hee-Jeong;Kim, Dong-Hyun;Jeong, Myeon-Woo;Ma, Tangen;Kim, Seong-Youl;Ho, Ing K.;Oh, Sei-Kwan
    • 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.

Effects of Glycine on the Development of Analgesic Tolerance to and Physical Dependence on Morphine in Mice

  • Baik, Jong-Won;Hong, Jin-Tae;Yun, Young-Won;Oh, Ki-Wan
    • Toxicological Research
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    • v.19 no.4
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    • pp.311-314
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    • 2003
  • This study was performed to investigate the effects of glycine on the development of tolerance to and physical dependence on morphine. Repeated administration of morphine (10 mg/kg) developed tolerance and physical dependence. Glycine (100, 200 and 400 mg/kg) was administered intraperitoneally (i.p.) to mice for 7 days prior to the morphine injection. Analgesic effects were estimated by the tail flick methods. The inhibitory degree of the development of morphine-induced analgsic tolerance by i.p. administration of glycine was evidenced by the increase in analgesic response to morphine. Glycine inhibited the development of tolerance to morphine. In addition, we separately measured jumping response as the naloxone-precipitated withdrawal sign in mice that had received the same morphine. Glycine reduced the number of jumping behaviors in morphine dependent mice. These results suggest that glycine might be useful the prevention or treatment of morphine tolerance and physical dependence.

Effects of Panax Ginseng on the Development of Morphine Induced Tolerance and Dependence (II) -Effects of Ginseng Butanol Fraction on the Development of Morphine Induced Tolerance and Dopamine Receptor Supersensitivity in Rats- (Morphine의 내성(耐性) 및 의존성(依存性) 형성(形成)에 미치는 인삼(人蔘)의 효과(II) -인삼(人蔘)의 Butanol 분획이 흰쥐의 Morphine 내성(耐性) 및 Dopamine 수용체(受容體) 초과민성(超過敏性) 형성에 미치는 영향(影響)-)

  • Kim, Hack-Seang;Oh, Sei-Kwan;Kim, Gap-Cheol
    • Korean Journal of Pharmacognosy
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    • v.16 no.1
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    • pp.31-35
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    • 1985
  • Intraperitoneal administration of ginseng butanol fraction(GBF) to chronic morphinization in male Sprague-Dawley rats inhibited the development of tolerance to the analgesic effect and hyperthermic action of morphine. Rats were rendered tolerant to morphine by subcutaneous multiple morphine injections for a period of 8 days. The development of tolerance was evidenced by the decreased analgesic response to morphine and inhibition of tolerance by the greater analgesic response. Concomitant administration of morphine with GBF blocked the tolerance to the hyperthermic effect of morphine as evidenced by elevation of body temperature by morphine. Dopamine receptor sensitivity was enhanced in morphine tolerant rats as measured by apomorphine induced in spontaneous motor activity. GBF administration also blocked dopamine receptor supersensitivity induced by chronic morphinization.

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Effects of Coptis japonica on Morphine-Induced Conditioned Place Preference in Mice

  • Lee, Seok-Yong;Song, Dong-Keun;Jang, Choon-Gon
    • Archives of Pharmacal Research
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    • v.26 no.7
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    • pp.540-544
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    • 2003
  • Morphine, an analgesic with significant abuse potential, is considered addictive because of drug craving and psychological dependence. It is reported that repeated treatment of morphine can produce conditioned place preference (CPP) showing a reinforcing effect in mice. CPP is a useful method for the screening of morphine-induced psychological dependence. In the present study, we investigated the effect of the methanolic extract of Coptis japonica (MCJ) on morphine-induced CPP in mice. Furthermore, we examined c-fos expression in the parietal cortex, piriform cortex, striatum, nucleus accumbens, and hippocampus of the morphine-induced CPP mouse brain. Treatment of MCJ 100 mg/kg inhibited morphine-induced CPP. Expression of c-fos was increased in the cortex, striatum, nucleus accumbens, and hippocampus of the morphine-induced CPP mouse brain. These increases of expression were inhibited by treatment with MCJ 100 mg/kg, compared to the morphine control group. Taken together, these results suggest that MCJ inhibits morphine-induced CPP through the regulation of c-fos expression in the mouse brain.

Effects of Ginseng Saponins on Morphine 6-Dehydrogenase

  • 김학성;정인숙;이명구;오기완
    • Proceedings of the Korean Society of Applied Pharmacology
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    • pp.304-304
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    • 1994
  • The possible mechanisms of ginseng saponins on the inhibition of development of morphine tolerance and physical dependence were investigated in the aspects of morphine metabolism by morphine 6-dehydrogenase. Administration of morphine causes a reduction of non-protein sulfhydryl contents in liver, because morphinone is metabolized from morphine by morphine 6-dehydrogenase conjugates with sulfhydryl compounds. However, ginseng saponins inhibited the activity of morphine 6-dehydrogenase which catalized the production of morphinone from morphine. In addition, ginseng' saponins inhibited the reduction of non-protein sulfhydryl levels by Increasing the level of hepatic glutathione. These results suggest that the dual action of the above plays an important role in the inhibition of development of morphine tolerance and physical dependence. On the other hand, it was observed that less polar components of ginseng saponins with parent structures were more active components in vitro.

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Effects of Berberine on Morphine-induced Neurotoxicity in Mice

  • Jang, Choon-Gon
    • Proceedings of the PSK Conference
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    • pp.112-112
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    • 2003
  • Morphine is a potent analgesic and addictive substance. Morphine produces neurotoxicity such as rewarding effect, analgesic tolerance and physical dependence. It has been restricted to the use of morphine in patients because of these problems. The present study was investigated the effect of berberine on the neurotoxicity of morphine. Repeated administration of morphine produced conditioned place prefernece (CPP) and behavioral sensitization in mice. (omitted)

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