• Biomolecules & Therapeutics
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• 제5권2호
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• pp.133-149
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• 1997

4-week repeated dose toxicity of DA-5018, a new capsaicin analogue analgesic agent, was examined in 5D rats at dosage levels of 0,0.4,2, 10 and 50 mg/kg/day. DA-5018 was administered orally to 17 males and 17 females per group at doses of 0, 10 and 50 mg/kg and to 12 males and 12 females per group at doses of 0.4 and 2 mg/kg. After the administration period, 5 males and 5 females at the 0, 10 and 50 mg/kg were placed on withdrawal for 2 weeks. Treatment-related clinical signs were observed at 10 and 50 mg/kg. Clinical signs observed immediately after the administration of DA-5018 were grooming, sedation or depression, lacrimation, atacia, reddening of extremities and ears, ventral or lateral recumvincy, respiratory distress, cyanosis and convulsion. Delayed-type clinical signs including focal scabbing and depilation around nose were also observed 1 or 2 weeks after the start of administration of DA-5018. Only at the 50 mg/kg group, corneal opacities, reduced body weight gain (male) and death (male 6/17, female 3/17) were noted. In blood biochemical analysis, serum levels of glucose and triglyceride decreased at 10 and 50 mg/kg. In hematological examination, there were increases in the number of red blood cell, hemoglobin content and percent of hematocrit at 10 and 50 mg/kg. Pulmonary enlargement and hemorrhagic spot, focal scabbing and depilation around nose and corneal opacities were seen at the necropsy of the animals died during the dosing of DA-5018 50 mg/kg. Focal scabbing and depilation around nose were observed in the animals terminally necropsied at doses of 10 and 50 mg/kg. Histopathological examination revealed pulmonary hemorrhage, focal necrosis in the scabbed area, corneal necrosis, fibrosis and neovasculization in the stroma. At 0.4 and 2 mg/kg, there were no significant toxic changes attributable to the administration of DA-5018. In conclusion, target organs following to 4-week repeated dose of DA-5018 in the rat were determined to be lung, skin and eyes. Definite toxic dose and no-observed-adverse-effect-level (NOAEL) were estimated to be 50 and 2 mg/kg/day, respectively.

• Biomolecules & Therapeutics
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• 제4권4호
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• pp.391-397
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• 1996

The aim of this study was to assess the allergenic potential of 0.3% DA-5018 cream, a non-narcotic analgesic agent, using a guinea pig maximization test. Five male and female guinea pigs in the experimental group were sensitized in two steps. First, ,0.3% DA-5018 cream was injected intradermally, and 7 days later, the material was applied topically. After another 2 weeks test material was applied, the skin response was evaluated by visual observation. Five male and female guinea pigs served as cream base group, negative(ultreated) group or positive (2,4-dinitrochlorobenzene, DNCB) group, respectively. 0.3% DA-5018 cream provoked slight erythema in 1 out of 5 cases in male and female guinea pigs sensitized with 0.3% DA-5018 cream or cream base. The animals challenged with cream base also showed slight erythema in 1/5 female guinea pig sensitized with 0.3% 3A-5018 cream or 2/5 male guinea pjgs sensitized with cream base, respectively. Histologically, however, no indication of skin sensitization was observed in all of these cases. The positive control group was sensitized with 0.1% DNCB suspended in olive oil and challenged with 0.01% and 0.1% DNCB ointment, all the animal showed remarkable skin reactions and obvious skin sensitization reactions in a dose dependent manner. From the challenge test it was evident that 0.3% DA-5018 cream did not elicit positive skin reaction interpreted as delayed hypersensitivity reactions, compared with cream base or untreated control group. These findings indicate that allergenic side effects by 0.3% DA-5018 cream is not likely in the clinical use.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2001년도 추계학술대회 및 정기총회
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• pp.93-93
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• 2001

Loxoprofen sodium is an orally used anti-inflammatory, analgesic and antipyretic agent. For alleviation or inhibition of the pain symptoms regardless of referred or superficial pain, the prompt absorption of a drug and its immediate bioavailability might be generally required for a formulation or development of a new drug. Therefore, in intramuscular administration, its anti-inflammatory, analgesic, and antipyretic effects were evaluated compared with an oral administration in animals. The occurrence of gastric damages which is common in nonsteroidal anti-inflammatory drugs was also observed.

• Natural Product Sciences
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• 제17권3호
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• pp.256-260
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• 2011

Polygoni multiflori Ramulus, the stem of Polygonum multiflorum Thunb., has been widely used as a traditional medicine for the treatment of many diseases. Presently, antinociceptive tests of the butanolic fraction of P. multiflorum (SPB) were performed using several thermal and chemical pain models. SPB had strong and dosedependent antinociceptive activities, both thermal and chemical, compared to the reference drugs Tramadol and Indomethacin. In combination with naloxone, the analgesic activity of SPB was unchanged indicating that the antinociceptive activity of SPB was not due to action as an opioid receptor agonist. The present results indicate the potential of SPB as an analgesic agent for pain control.

• 생약학회지
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• 제25권3호
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• pp.258-263
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• 1994

Ohjuksan has been used for the treatment of cold and pantalgia in traditional medicine. The anti-inflammatory activity of the aqueous extract from Ohjuksan (OJSE) was investigated utilizing acetic acid-induced edema and adjuvant arthritis in rats. The effects of this agent on acute toxicity and acetic acid-induced writhing syndrome in mice were also examined. OJSE did not showed acute toxicity at 2400mg/kg (p.o.) and 1200mg/kg(i.p.) body weight. It was also showed to have significant analgesic action on the writhing syndrome in mice induced by 0.7% acetic acid at 300,600mg/kg body weight. It showed anti-inflammatory activity in 5% acetic acid-induced edema and adjuvant arthritis with oral administration in rats and exhibited significant preventive effect on edema at 300 and 600mg/kg(p<0.01). In the method of adjuvant arthritis, orally administered for 19 days, it inhibited the hind paw edema in rats with 300 and 600 mg/kg body weight from 5 th day to 19th day. These results suggest that OJSE had analgesic and anti-inflammatory action.

• 생약학회지
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• 제36권4호통권143호
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• pp.338-343
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• 2005

Inflammatory mediators such as interleukin-1 (IL-1), tumor necrosis $factor-{\alpha}\;(TNF-{\alpha}),\;interferon-{\gamma}\;(IFN-{\gamma})$ and lipopolysaccharide (LPS) are thought to play major roles in joint diseases such as a rheumatoid arthritis (RA), and there is considerable evidence playing a role for these cytokines in osteoarthritis (OA). Therefore, we have studied the effects on anti-inflammation and analgesic by ethyl acetate fraction from 70% ethanol extract of Artemisia capillaries (EAC). As a positive control, apigenin, which is known as an anti-inflammatory agent as an iNOS inhibitor, was used and showed the dose-dependent inhibitory effect. EAC showed strong inhibitory efficacy against cytokine-induced proteoglycan degradation, $PGE_2$ production, nitric oxide (NO) production, and matrix-matalloproteinases (MMPs) expression in rabbit articular chondrocyte. In the writhing test induced by acetic acid, EAC $(200{\sim}400\;mg/kg)$ exhibited a dose-dependent inhibition of writhing. The results indicate that EAC have anti-inflammatory and analgesic activities, and could be a good herbal medicine candidate for curing of RA and/or OA.

• 약학회지
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• 제43권3호
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• pp.320-327
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• 1999

Six novel aryl alkanoic acid derivatives as potential nonsteroidal antiinflammatory and analgesic compounds, were prepared through consecutive reactions of Ullman ether synthesis, $NaBH_4$ reduction ; bromination ; $SN_2$ reaction with nitrile and alkaline hydrolysis of the nitrile.

• Biomolecules & Therapeutics
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• 제5권1호
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• pp.12-22
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• 1997

Intravenous and oral acute toxicity tests in ICR mice and SD rats and percutaneous acute toxicity tests in SD rats and NZW rabbits were conducted to evaluate the toxicity of DA-5018 and DA-5018 cream, respectively Clinical signs observed in mice and rats after the administration of DA-5018 were similar regardless of administration route. The observed clinical signs were jumping, wild running, lacrimation, ataxia, reddening of extremities and ears, ventral or lateral recumbency, respiratory distress, cyanosis, convulsion and death. Pulmonary enlargement and hemorrhage were observed in the animals died immediately after the dosing of DA-5018. At terminal necropsy, pulmonary enlargement and hemorrhage, corneal opacity and focal scabbing and depilation around nose were seen. LD$_{50}$ Values of DA-5018 are 11.5 mg/kg (mice, male), 12.6 mg/kg (mice, female), 88.3 mg/kg (rat, male) and 73.2 mg/kg (rat, female) in oral toxicity tests and 11.0 mg/kg (mice, male), 18.7 mg/kg (mice, female), 0.12 mg/kg (rat, male) and 0.32 mg/kg (rat, female) in i.v. toxicity tests. In the percutaneous acute toxicity tests of DA-5018 cream, no deaths occured in all the tested groups during 14-day observation period. There were also no abnormalities in the general conditions, body weight changes and on necropsy findings in all groups. LD$_{50}$ values of 0.1 ~0.9% DA-5018 creams in male and female rats and rabbits are >2000 mg/kg./kg.

• The Korean Journal of Pain
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• 제32권2호
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• pp.79-86
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• 2019

Background: The use of aroma oils dates back to at least 3000 B.C., where it was applied to mummify corpses and treat the wounds of soldiers. Since the 1920s, the term "aromatherapy" has been used for fragrance therapy with essential oils. The purpose of this study was to determine whether the essential oil of Eucalyptus (EOE) affects pain pathways in various pain conditions and motor coordination. Methods: Mice were subjected to inhalation or intraperitoneal injection of EOE, and its analgesic effects were assessed by conducting formalin, thermal plantar, and acetic acid tests; the effects of EOE on motor coordination were evaluated using a rotarod test. To determine the analgesic mechanism, 5'-guanidinonaltrindole (${\kappa}$-opioid antagonist, 0.3 mg/kg), naltrindole (${\delta}$-opioid antagonist, 5 mg/kg), glibenclamide (${\delta}$-opioid antagonist, 2 mg/kg), and naloxone (${\mu}$-opioid antagonist, 4, 8, 12 mg/kg) were injected intraperitoneally. Results: EOE showed an analgesic effect against visceral pain caused by acetic acid (EOE, 45 mg/kg); however, no analgesic effect was observed against thermal nociceptive pain. Moreover, it was demonstrated that EOE did not have an effect on motor coordination. In addition, an anti-inflammatory effect was observed during the formalin test. Conclusions: EOE, which is associated with the ${\mu}$-opioid pain pathway, showed potential effects against somatic, inflammatory, and visceral pain and could be a potential therapeutic agent for pain.

• 한국임상약학회지
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• 제28권4호
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• pp.279-284
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• 2018

Objective: To compare the analgesic effects and adverse drug reactions (ADRs) of fentanyl intravenous patient-controlled analgesia (ivPCA) with nefopam, a centrally acting analgesic agent with demonstrated opioid sparing activity, as compared to ketorolac in a tertiary teaching hospital. Methods: A retrospective evaluation of electronic medical records was conducted on patient records including either nefopam or ketorolac with opioid ivPCA for post-operative pain management in general surgery department from January to December 2014. The status of pain control and ADRs were collected. Results: Out of 6,330 general surgery cases, nefopam was given in 153 prescriptions (6.9%) and ketorolac in 81 prescriptions (3.6%). The level of pain control was not different between two groups (70.9% vs. 75.3%; p = 0.51), but ADRs were more frequently reported in nefopam group (9.8% vs. 2.5%; p < 0.05). New ADRs of hot flushes (n = 1) and paresthesia in hands (n = 1) were reported in nefopam group and they were unlisted in the approved package insert. No serious ADRs were reported in both groups. Conclusion: Our findings presented that nefopam showed a similar analgesic effect and higher ADR rates compared to ketorolac as an adjuvant to fentanyl iv PCA for post-operative pain management in general surgery patients in South Korea.