• 대한약학회:학술대회논문집
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• 대한약학회 2000년도 춘계총회 및 학술대회
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• pp.70-81
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• 2000

DA-5018 is a synthetic capsaicin derivative under development as a non-narcotic a analgesic ag$\varepsilon$nt. DA-50 18 showed a potent analgesic activity against acute and chronic pain m model(Tablel, 2.), but it had a narrow margin of safety. DA-5018 did not bind to opioid(${\kappa}, {\delta}, {\mu}$), NKl, CGRP receptors in vitro and its analgesic effect was not antagonized by naloxone, a and it did not develop analgesic tolerance. In addition DA-5018 had no inhibitory effects against c cyclooxygenase and 5-lipooxygenase activities. DA-5018 significantly increased the relcase of substance P from the slices of the rat spinal cord. These results suggest that DA-50 18 is not a narcotic nor aspirin-like analgesic and the release of substance P is one of analgesic mechanism of action of DA-5018. We found that DA-5018 was almost ten times more potent and was at l least IOO-times less irritable compared to capsaicin. Accordingly development of topical formula was adopted. Topical formula was desiged and screened by flux test of DA-5018 using hairless mouse skin and several formulas were selected. With these topical formulas we a assessed the analgesic efficacy and carried out the toxicity, skin irritation and pharmacokinetic studies. In streptozotocin-induced hyperalgesic rat and 50 % galactose-fed hyperalgesic rat as diabetic pain models, DA-5018 cream increased the pain thresh이ds up to 77.0% and 24.4% respectively, while Zostrix-HP(capsaicin cream) incr$\varepsilon$as cd by 65.9% and 21.0%. DA-5018 c cream showed a good analgesic effect as welI in FCA-induced arthritic rat. DA-5018 cream did not show any toxicological signs in acute and chronic toxicity test and had little skin irritation in car swclIing and scratching t$\varepsilon$st. Pharmacokinetics of DA-50 18 were studied after topical application of ${14}^C$-Iabelled or unlabelIed DA-5018 cream. Plasma and skin concentrations c except applied skin wcre below the dctection limit and after 7-day cummulative application, plasma concentrations were also below detection limit DA-50 18 may have an advantag$\varepsilon$ ov$\varepsilon$r c capsaicin and is now being developed as a topical agent for the treatment of pains. DA-50 18 cream was approved for Korean IND and is now under a Phase II clinical study for arthritic pain a after finising Phase I study. DA-50 18 was also liscensed out to Stiefel Company in America in

• Journal of Ginseng Research
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• 제23권4호
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• pp.239-246
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• 1999

백서를 이용하여 진세노사이드 흑은 모르핀을 척수강내 투여한 다음 tail-flick test를 통하여 진통 작용을 연구하였다. 또한, 진세노사이드를 모르핀과 함께 척수강내 장기 처리할 경우 모르핀에 의한 내성 및 의존성 유발에 미치는 영향을 연구하였다. 연구 결과, 척수강내 진세노사이드의 투여는 200 ${\mu}g$/rat에서 약한 진통 작용이 있는 것으로 나타났다. 모르핀은 투여 농도에 의존적으로 좋은 진통 효능을 보여주었으며, $ED_50$은 1.2 ${\mu}g/rat$인 것으로 나타났다. 그러나 진세노사이드의 모르핀을 함께 척수강내 투여할 경우 모르핀의 진통 작용을 증가 시키지 않은 것으로 나타났다. 200 ug/rat 진세노사이드를 10 ${\mu}g$/rat모르핀을 7일 동안 같이 투여할 경우 모르핀에 의한 통증 작용에 대한 내성을 억제하였으며, 모르핀에 의한 의존성을 부분적으로 억제하는 것으로 나타났다. 이러한 연구 결과는 척수 수준에서 진세노사이드가 모르핀의 장기 투여에 의하여 유도되는 모르핀에 대한 내성 및 의존성을 억제하는 것으로 사료된다.

• Biomolecules & Therapeutics
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• 제18권2호
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• pp.159-165
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• 2010

Alpinia katsumadai has been widely used in traditional Chinese and Korean medicine to treat a variety of conditions including emesis and gastric disorders such as gastric pain and distended abdomen. To investigate the antinociceptive potential and mechanism of A. katsumadai, ethanolic extracts of A. katsumadai were assayed on cyclooxygenase-2 and evaluated for analgesic activity based on phenylbenzoquinone (PBQ)-induced writhing and carrageenan-induced hyperalgesia tests. A. katsumadai extracts inhibited the cyclooxygenase-2 enzyme activity in a dose-dependent fashion at an $IC_{50}$ value of 0.044 ${\mu}g$/ml. A. katsumadai extract (30-300 mg/kg, orally (p.o.) administered) significantly inhibited PBQ-induced writhing. This inhibition was judged not to be a false positive because a Rota-rod test revealed no difference in muscular coordination when compared to the controls. With regard to the carrageenan-induced hyperalgesia, A. katsumadai extract (30-300 mg/kg, p.o.) produced a significant, dose-dependent increase in the withdrawal response latencies. Naloxone did not reverse the analgesic effect of A. katsumadai extract in the carrageenan-induced hyperalgesia. Taken together, these results suggest that the antinociceptive activity of A. katsumadai is not related to the opioid receptor. A. katsumadai extract has remarkable, non-opioidreceptor-mediated analgesic effects on PBQ-induced writhing and carrageenan-induced hyperalgesia that occur via cyclooxygenase-2 inhibition.

• Journal of Acupuncture Research
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• 제20권4호
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• pp.11-23
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• 2003

Objective: In this study, the analgesic effect of gold injection aqua-acupuncture on CFA induced arthritis in rats was inverstigated. Furthermore, to determine the antinociceptive mechanism of gold injection aqua-acupuncture, naloxone and yohimbine were administrated intraperitoneally 15min prior to the gold injection aqua-acupuncture. Methods: The experimental groups were divided into 6 groups. Control group, NSI, AMI, AMI+SL : AMI+Nx, AMI+Yb. Thereafter we measured the chages of TFL between control and experimental groups. Results: 1. The tail flick latency induced by CFA was significantly increased on AMI as compared with the NSI group. 2. Effect of sodium aurothiomalate aqua-acupuncture in TFL on CFA was decreased after application of naloxone. The anti-nociceptive effect of AMI was completely antagonized by naloxone(an opioid receptor antagonist). 3. Effect of sodium aurothiomalate aqua-acupuncture in TFL on CFA was decreased after application of yohimbine. The anti-nociceptive effect of AMI was completely antagonized by yohimbine(${\alpha}2$-adrenoceptor antagonist). Conclusions: According to the results, gold injection aqua-acupuncture has significant analgesic effects on adjuvant induced arthritis in rats and the effect of anti-nociception was mediated by opiodergic system and ${\alpha}2$-adrenergic system.

• Advances in Traditional Medicine
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• 제6권4호
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• pp.349-354
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• 2006

In the present study, three Malaysian Channa spp. fish Channa striatus, Channa micropeltes and Channa lucius were assessed for their analgesic activity. Distilled water and mixture of chloroform: methanol were used for extraction. The analgesic or antinociceptive activity was investigated by abdominal writhing and hot plate test. The water extract of Channa striatus and the chloroform: methanol extract Channa lucius produced potent antinociceptive effect when assessed with the abdominal writhing test. The activity was compared to morphine where the activity of the extracts was less potent than the opioid. In the hote plate test, water extract of Channa striatus revealed significant activity and chloroform:methanol extract of Channa micropeltes had moderate activity. However, these activities were statistically lower than morphine. Collectively, this study also showed that Channa striatus extract was more potent analgesic agent when compared to the other closely related snakehead Channa micropeltes and Channa lucius.

• The Korean Journal of Pain
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• 제18권1호
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• pp.10-14
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• 2005

Background: Previous studies have suggested synergistic analgesic drug interactions between NSAIDs and opioids in neuropathic and inflammatory pain models. The aim of this study was to investigate the analgesic drug interaction between intraperitoneal (IP) ketorolac and morphine in radiant thermal stimulation rat. Methods: Initially, we assessed the withdrawal latency time of the hindpaw to radiant thermal stimulation every 15 min for 1 hour and every 30 min for next 1 hour after IP normal saline 5 ml (control group). The latency time was changed into percent maximal possible effect (%MPE). Next, IP dose response curves were established for the %MPE of morphine (0.3, 1, 3, 10 mg/kg) and ketorolac (3, 10, 30 mg/kg) to obtain the $ED_{50}$ for each agent. And we confirmed that the IP morphine effect was induced by opioid receptor through IP morphine followed by IP naloxone. At last, we injected three doses of IP ketorolac (3, 10, 30 mg/kg) mixed with one dose of morphine (2 mg/kg) for fixed dose analysis. Results: IP morphine delayed the paw withdrawal latency time dose dependently, but not ketorolac. $ED_{50}$ of IP morphine was 2.1 mg/kg. And the IP morphine effect was reversed to control level by IP naloxone. IP ketorolac + morphine combination showed no further additional effects on paw withdrawal latency time over morphine only group. Conclusions: IP ketorolac did not produce antinociceptive effect during radiant thermal stimulation. There was neither additional nor synergistic analgesic interaction between IP morphine and ketorolac in thermal stimulation rat.

• 고려인삼학회:학술대회논문집
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• 고려인삼학회 1990년도 Proceedings of International Symposium on Korean Ginseng, 1990, Seoul, Korea
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• pp.36-44
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• 1990

The analgesic effect of morphine was antagonized and the development of tolerance was suppressed by the modification of the neurologic function in the animals treated with ginseng saponins. The activation of the spinal descending inhibitory systems as well as the supraspinal structures by the administration of morphine was inhibited in the animals treated with ginseng saponins intracerebrally or intrathecally The development of morphine tolerance and dependence, and the abrupt expression of naloxone induced abstinence syndrome were also inhibited by ginsenoside Kbl , Rba, Rgl and Re. These results suggest that ginsenoside Kbl, Rba, Rgl and Re are the bioactive components of panax ginseng on the inhibition of the development of morphine tolerance and dependence, and the inhibition of abrupt abstinence syndrome. In addition, further research on the minor components of Panax ginseng should be investigated. A single or daily treatment with ginseng saponins did not induce any appreciable changes in the brain level of monoamines at the various time intervals and at the various day intervals, respectively The inhibitory or facilitated effects of ginseng saponins on electrically evoked contractions in guinea pig ileum (U-receptor) and mouse was definers (5·receptor) were not mediated through opioid receptors. The antagonism of a x receptor agonist, U-, iO.488H was also not mediated through opioid receptors in the animals treated with ginseng saponins, bolt mediated through serotonergic mechanisms. Ginseng saponins inhibited morphine S-dehydrogenase that catalyzed the production of morphine from morphine, and increased hepatic glutathione contents for the detoxification of morphine. This result suggests that the dual action of the above plays an important role in the inhibition of the development of morphine tolerance and dependence.

• 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.

• 대한한의학회지
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• 제24권4호
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• pp.34-42
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• 2003

This study was designed to investigate the modulation of the Corydalis tuber on glycine-activated ion current in rat periaqueductal gray (PAG) neurons. Aqueous extract from Corydalis tuber has been widely used for pain control such as dysmenorrhea, irregular menstruation or amenorrhea with abdominal cramping, neuralgia, headache and gastrointestinal spasm. The PAG region of the brain is known to be involved heavily with nociception. Modulation of the Corydalis tuber on glycine-induced ion current in rat periaqueductal gray (PAG) neurons was studied by a nystatin-perforated patch-clamp technique. High concentrations of Corydalis tuber elicited ion current, which was suppressed by strychnine application. Low concentrations of Corydalis tuber reduced glycine-induced ion currents in the PAG neurons. Inhibitory action of Corydalis tuber on glycine-activated ion current was reduced by treatment with naltrexone, a non- selective opioid antagonist. Application of N-methylmalemide (NEM), a sulfhydryl alkylating agent, also reduced the inhibitory action of Corydalis tuber on glycine-activated ion current in the PAG neurons. These results suggest that the inhibitory effect of Corydalis tuber on glycine-activated ion current in the PAG neurons is one of the analgesic mechanisms of the Corydalis tuber, which may activate descending pain control system in PAG neurons.

• The Korean Journal of Pain
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• 제21권1호
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• pp.51-56
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• 2008

Background: Preoperative dexamethasone improves the surgical outcome after laparoscopic cholecystectomy(LC). The purpose of this study was to determine the effect of preoperative dexamethasone on the postoperativepain according to age and gender in patients who undergo LC.Methods: In this double blind prospective study, 400 patients, males or females :< 45 yr and males or femaless 65 yr (n = 50 in each of eight groups) who undergoing LC were randomized to receive dexamethasone 8mg (5 ml) or saline 5 ml intravenously 100 minutes before their operation, Postoperative pain was assessedon a visual analog scale (VAS) at 1, 6, 12, and 24 hour, and the time to administering the first postoperativeanalgesics was recorded.Results: Dexamethasone was administered without consideration for age and gender, and it reduced thepostoperative pain VAS score at 1, 6, and 12 hours, and the opioid analgesic requirement, but there was nosignificant difference between administering saline or dexamethasone in the same gender and age groups.Females U 45 yr who were administered saline had the most pain sensitivity and males S 65 yr who wereadministered dexamethasone had the least pain sensitivity.Conclusions: Preoperative dexamethasone reduces the pain intensity and opioid consumption, but does notreduce the pain intensity, according to age and gender in the patients undergoing LC. As a result, Preoperativedexamethasone should be considered for routine use for patients who are undergoing laparoscopic cho-lecystectomy. (Korean J Pain 2008; 21: 51 56)