• 대한약리학회지
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• 제30권1호
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• pp.11-18
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• 1994

Opioid수용체는 adenylate cyclase의 활성을 억제하므로써 cyclic AMP의 양을 감소시킨다. 본 연구에서는 striatum에서 dopamine과 opioid 신경전달계의 상호관계를 알아보고자 haloperidol(750ug/kg)을 10일간 복강내 투여하여 dopaminergic pathway를 차단시킨후 mouse striatum에서 선택적 opioid ${\mu},\;{\gamma}\;{\kappa}$ 수용체 agonist들에 의해 축적되는 cAMP양을 측정하여 본 결과, haloperidol단독투여에 의해서 cAMP는 유의한 증가를 나타내었으며, haloperidol 장기투여된 mouse striatum 에서 morphine(20mg/kg), DAGO(5Oug/kg), DPDPE(50ug/kg), U5O,488H (500ug/kg)투여에 의해서 haloperidol에 의한 cAMP 증가는 억제되었으며, 정상 mouse에 투여된 morphine, DAGO, DPDPE, U5O,488H에 비해서는 DAGO, DPDPE 투여군에서 증가를 나타내었다. Haloperidol장기투여로 인한 morphine, DAGO, DPDPE, U5O,488H의 영향은 naloxone에 의해서 morphine과 U5O, 488H투여군에서 길항되었으며 정상 mouse에 투여된 morphine, DAGO, DPDPE, U5O,488H에 의한 cAMP의 감소는 naloxone에 의하여 모든 실험군에서 길항되었다. 이상의 결과로 보아 dopaminergic denervation시 mouse striatum에서 ${\mu},\;{\gamma},\;{\kappa}$효현제에 의하여 축적되는 cAMP양은 ${\kappa}$수용체 효현제인 U5O,488H에서 가장 현저한 감소를 보여 각 수용체의 활성화정도는 변화되며, 그중에서 ${\kappa}$수용체는 그 기능이 가장 보존되고 있음을 알 수 있었다.

• 대한임상독성학회지
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• 제10권1호
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• pp.33-36
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• 2012

Opioids are the one of the most commonly used drugs to control cancer pain all over the world. But, we should not overlook the potential risk of opioid intoxication because they have well-known detrimental side effects. The opioid intoxication can be diagnosed thorough various clinical manifestations. The altered mental status, respiratory depression, and miosis is very representative clinical features although these symptoms don't always appear together. Unfortunately the opioid-toxidrome can be varied. A 42 years old man came to our emergency room after taking about 900 mg morphine sulfate per oral. He was nearly alert and his respiration was normal. Even though his symptoms didn't deteriorated clinically, serial arterial blood gas analysis showed increase in PaCO2. So we decided to use intravenous naloxone. Soon, he was fully awaked and his pupils size was increased. After a continuous infusion of intravenous naloxone for 2 hours, PaCO2 decreased to normal range and his pupil size also returned to normal after 12 hours. Though the levels of serum amylase and lipase increased slightly, his pancreas was normal according to the abdominal computed tomography. He had nausea, vomit, and whole body itching after naloxone continuous infusion, but conservatively treated. We stopped the continuos infusion after 1 day because his laboratory results and physical examinations showed normal. As this case shows, it is very important to prescribe naloxone initially. If you suspect opioid intoxication, we recommend the initial use of naloxone even though a patient has atypical clinical features. In addition, we suggest intranasal administration of naloxone as safe and effective alternative and it's necessary to consider nalmefene that has a longer duration for opioid intoxication.

• The Korean Journal of Pain
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• 제9권2호
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• pp.374-379
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• 1996

Background: Recently, improvements in drug administration technology have intensified interest in the treatment of postoperative pain. this has resulted in increased use of continuous intravenous infusion of opioid and epidural opioid as alternative to traditional intramuscular administration of opioid. The goal of this study, therefore, was to document the effects of pain control and side effects following continuous intravenous infusion of morphine or meperidine and intramuscular meperidine following cesarean section. Methods: The vital signs, pain score, oxygen saturation and side effects were compared in 150 patients receiving continuous intravenous infusion of morphine, 30 ${\mu}g/kg/hr$ (n=50, group 1); continuous intravenous infusion of meperidine, 150 ${\mu}g/kg/hr$ (n=50, group 2); or intramuscular meperidine, 50mg/every 6hrs (n=50, group 3). Results: VAS (Visual Analogue Scale) was significantly decreased after 30 minutes of administration in all three groups and was significantly lower at 1 hour, but higher at 6 hours in group 3 than two other groups. Severe desaturation episode, defined as $SpO_2$<90%, occurred in the group 3(0.2%). Moderate desaturation episodes, defined as $SpO_2$ 91~95%, occurred more in group 3 than in group 1 and 2 (17.4% vs. 10.4%, 8.2%). The incidence of side effects were similar among three groups. Conclusion: The continuous infusion of opioid was more effective and safe method of postoperative pain control than traditional intramuscular injection.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1994년도 춘계학술대회 and 제3회 신약개발 연구발표회
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• pp.50-62
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• 1994

Opium, morphine and rotated natural and synthetic opiates have been used since antiquity, and to the present, for the relief of moderate and severe pain. Morphine and pharmacologically related drugs, however, produced an array of undesired or dangerous side effect that limit their use as analgesics. Prominent among the limiting side effects are constipation, respiratory depression, release of prolactin, and liability for the production of drug dependence. It was our aim to develop, if possible, a drug or class of drugs with analgesic activity similar to that of morphine, but without the serious side effects associated with morphine. Our overall strategy was to take advantage of advancing knowledge concerning multiple types of opioid receptors, to develop ligands selective for the delta type receptors, to determine whether delta receptor agonists offer advantages over mu agonists, then to design compounds with pharmacokinetic properties compatible with practical therapeutic application. All but the last of these objectives have been realized.

• The Korean Journal of Pain
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• 제13권2호
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• pp.218-223
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• 2000

Background: This study was conducted to evaluate the efficacy of a parenteral nonsteroidal anti-inflammatory agent for management of post-surgical pain and its effect on hospital stay and long-term surgical outcome. Methods: Total of 40 patients undergoing lumbar discectomy were randomly assigned to two groups, receiving either 1) 30 mg intravenous ketorolac upon surgical closure, every 6 hours for 36 hours, and morphine IV PCA (intravenous patient controlled analgesia), or 2) only morphine PCA. A blinded investigator recorded; the visual analog pain scores, total postoperative narcotic consumption, complications by morphine PCA, length of hospitalization (from surgery to discharge), and long-term outcome at 6 weeks. Results: The patients who received IV ketorolac and morphine PCA reported significantly lower visual analog pain scores than patients receiving only morphine PCA. Cumulative morphine doses were significantly lower in the ketorolac group (P<0.001). There was no significant difference between groups in the frequency of side effects related to morphine PCA. Mean length of hospitalization was longer for patients receiving only morphine PCA, but there was no statistical significance. Six weeks after surgery, four (20.0%) patients who received only morphine PCA suffered persistent back pain. In contrary, all those patients who received ketorolac were free of back pain at follow-up (P<0.05). Conclusions: These results suggest that intermittent IV bolus ketorolac, when used with opioid IV PCA is more effective than opioid IV PCA alone for postoperative pain following lumbar disc surgery. However, this strategy did not contribute to early discharge from hospital after lumbar disc surgery. The effect to long-term surgical outcome was not conclusive.

• Asian Pacific Journal of Cancer Prevention
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• 제15권12호
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• pp.4983-4988
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• 2014

Background: In Muslim majority countries (MMC) opioid use for pain management is extremely low. The underlying factors contributing to this are not well defined. Aim: The aim of this study was to survey the attitudes of cancer patients towards morphine use for pain management in a MMC and identify the factors that influence patient decisions to accept or refuse morphine as treatment for cancer pain. Settings/participants: Patients were questioned whether they had pain or not, the severity and the medications for pain management. Questions included what type of medication they thought morphine was, whether or not they would be willing to take morphine if recommended for pain management and the basis for their decision if they were against morphine use. Results: Four hundred and eighty-eight patients participated in the study. Some 50% of the patients who refused morphine use and 36.8% of the patients who would prefer another drug, if possible, identified fear of addiction as the basis for their decision. Reservation of morphine for later in their disease was the case for 22.4% of the patients who refused morphine use. Only 13.7 % of the patients refusing morphine and 9.7% of the patients who preferred another drug, if possible, cited religious reasons as the basis for this decision. Conclusions: Identifying the underlying factors contributing to low opioid use for pain management in MMC is important. Once the underlying factors were identified, all efforts should be taken to overcome them as they are barriers to improving patient pain management.

• 대한약리학회지
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• 제28권2호
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• pp.181-190
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• 1992

흰쥐 적출관류 부신에서 선택적인 nicotine 수용체 효능약인 DMPP(1,1-dimethyl-4-phenylpiperazinium)와 acetylcholine(ACh)의 카테콜아민(CA) 분비작용에 대한 opioids의 영향을 연구하고자 시행하여 얻어진 연구결과는 다음과 같다. Methionine-enkephalin$(9.68{\times}10^{-6}\;M)$으로 전처치시 DMPP(100 uM)과 $ACh(50\;{\mu}g)$에 의한 CA 유리작용이 현저히 억제되었으며 basal CA release는 영향을 받지 않았다. Morphine$(1.73{\times}10^{-5}\;M)$으로 전처치시 DMPP 및 excess $K^+$의 CA 분비작용은 뚜렷이 약화되었다. Morphine 역시 그자체는 basal CA release에는 영향을 미치지 않았다. Opiate 수용체 길항제인 naloxone$(1.22{\times}10^{-7}\;M)$은 DMPP 및 ACh에 의한 CA 분비작용을 현저히 차단 하였으나 basal CA release에는 영향을 미치지 못하였다. 이와 같은 연구결과로 보아, 흰쥐 관류 부신에서 니코틴 수용체에 의한 CA 분비작용은 내인성 opioid peptide에 의해서 억제되며, 이는 부신에 존재하는 opiate 수용체 흥분작용에 기인되는 것으로 사료된다.

• The Korean Journal of Pain
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• 제13권1호
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• pp.49-54
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• 2000

Background: Evidence has accumulated that opioids can produce potent antinociceptive effects by interacting with opioid receptors in peripheral tissues. Bupivacaine has a potent analgesic effect with early peak onset in the postoperative period. The combination of intrapelvic bupivacaine and morphine has been suggested as an ideal analgesic after endoscopic pelvic surgery. Methods: Sixty patients scheduled for endoscopic pelvic surgery under general anesthesia were allocated randomly to three groups. Group 1 received normal saline 20 ml, group 2 received morphine 5 mg in normal saline 20 ml, and group 3 received morphine 5 mg in 0.25% bupivacaine 20 ml into the pelvic cavity. Postoperative pain was assessed using the visual analogue scale at 1, 2, 4, 8, and 24 hours after the intrapelvic instillation. Supplemental analgesic requirements, vital signs, and side effects were recorded for 24 hours. Results: Intrapelvic morphine and bupivacaine produced significant analgesia after endoscopic pelvic surgery. The patients in group 3 had lower pain scores than those in the group 1 and 2 at 1, 2 and 4th hours. There were no significant differences in the pain scores at 8 hours and 24 hours postoperatively between group 2 and 3. Supplemental analgesic requirements were significantly greater in the groups 1 and 2 than the group 3 for 24 hours. No significant side effects occurred. Conclusion: The intrapelvic instillation of morphine and bupivacaine is effective for the postoperative pain control in patients undergoing endoscopic pelvic surgery.

• Journal of Ginseng Research
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• 제13권2호
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• pp.239-241
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• 1989

Naloxone partially antagonized the analgesic effect of a large dose of morphine and inhibited the development of an acute type tolerance. Ginseng total saponins did not antagonize the analgesia of a large dose of morphine but inhibited the delrelopment of acute and delayed types tolerance. The morphine analgesia and the development of acute type tolerance were affected by the opioid receptor antagonist, naloxone, but the development of acute type tolerance was not. Ginseng total saponins partially inhibited the development of the delayed type tolerance that was not inhibited by naloxone, but also partially suppressed the development of the acute type tolerance that was completely inhibited by naloxone. These results imply that the partial inhibition of the development of the acute and delayed types tolerance by ginseng total saponins is not mediated by the opioid receptors.

• 고려인삼학회:학술대회논문집
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• 고려인삼학회 2005년도 창립30주년기념 추계 학술대회 및 정기총회
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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.