• Archives of Pharmacal Research
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• v.23 no.1
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• pp.72-78
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• 2000

The general pharmacological properties of YJA20379-1 2-dimethylamino-4,5-dihydrothiazolo[4,5:3,4]pyridol[1,2-a]benzoimidazole, a novel proton pump inhibitor with antiulcer activities were investigated in mice, rats, guinea pigs and rabbits. YJA20379-2 at oral doses of 50, 100 and 200 mg/kg did not affect the general behaviour, hexobarbital hypnosis and motor coordination in mice. The drug did not have analgesic or anticonvulsant action at 200 mg/kg. Locomotor activity and body temperature were not influenced at 100 mg/kg. At a concentration up to 2{\times}10^{-4} g/ml$, YJA20379-2 did not produce any contraction or relaxation of isolated preparations, such as the rat fundus, the guinea pig ileum and the rat uterus, and did not antagonize the contractile response to several spasmogens, such as histamine, acetylcholine, serotonin and oxytocin. At dosages up to 200 mg/kg p.o. YJA20379-2 did not affect the pupil size of mice. Intestinal propulsion of mice was not affected up to 200 mg/kg p.o. and the drug did not affect urinary excretion at 100 mg/kg p.o. These results indicate that at dosages up to 100 gm/kg p.o. YJA20379-2 was found not to affect this pharmacological profile. However, at 200 mg/kg the drug lowered body temperature and showed decreased in locomotor activity and urine volume.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1997.04a
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• pp.115-115
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• 1997

A new capsaicin analog modified with 4-hydroxyl and alkyl chain of capsaicin was a very potent antiinflammatory analgesic drug and may be clinically useful for those who have rheumatoid arthritis, diabetic neuropathy and cancer. The purpose of this study was to investigate histopathology after short and long term application of poloxamer-based gels, and percutaneous absorption of various topical formulations. Poloxamer-based gel was prepared by cold method using poloxamer 407. The poloxamer gels was applied to dorsal sites of hairless mouse skin during one week or one month for the evaluation of skin irritation. The applied site was then sectioned for histopathologic examination. The topical formulations were also prepared using CMC, HPMC, MC, carbopol and glycerylmono stearate. Skin variation of poloxamer gels was studied using excised hairless mouse, rat, hamster and human penis skin. Franz-type diffusion cells were used far skin penetration of drug against receptor phase filled with about 10$m\ell$ of 0.9% saline solution kept at 32$^{\circ}C$. The concentration of drug was determined by the reverse phased C18, Symmetry HPLC with fluorometeric detector. No skin erythema was observed after dorsal application of poloxamer-based gels for one week or one month. No histopathologic changes was also examined, suggesting no skin toxicity of poloxamer-based gels. The order of flux rate was HPMC > MC ( CMC > poloxamer >> glycerylmono stearate ( carbopol. There was a skin variation of poloxamer gels. The flux rate of poloxamer gels was highest in case of hairless mouse followed by rat, human and hamster skin. The Partial support-Ministry of Science and Engineering (HAN project).

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.14
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• pp.5659-5665
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• 2014

Background: To investigate the antioxidant value and anticancer functions of mitragynine (MTG) and its silane-reduced analogues (SRM) in vitro. Materials and Methods: MTG and SRM was analyzed for their reducing power ability, ABTS radical inhibition and 1,1-diphenyl-2-picryl hydrazylfree radicals scavenging activities. Furthermore, the antiproliferation efficacy was evaluated using MTT assay on K 562 and HCT116 cancer cell lines versus NIH/3T3 and CCD18-Co normal cell lines respectively. Results: SRM and MTG demonstrate moderate antioxidant value with ABTS assay (Trolox equivalent antioxidant capacity (TEAC): $2.25{\pm}0.02$ mmol trolox / mmol and $1.96{\pm}0.04$ mmol trolox / mmol respectively) and DPPH ($IC_{50}=3.75{\pm}0.04mg/mL$ and $IC_{50}=2.28{\pm}0.02mg/mL$ respectively). Both MTG and SRM demonstrate equal potency ($IC_{50}=25.20{\pm}1.53$ and $IC_{50}=22.19{\pm}1.06$ respectively) towards K 562 cell lines, comparable to control, betulinic acid (BA) ($IC_{50}24.40{\pm}1.26$). Both compounds showed concentration-dependent cytototoxicity effects and exert profound antiproliferative efficacy at concentration > $100{\mu}M$ towards HCT 116 and K 562 cancer cell lines, comparable to those of BA and 5-FU (5-Fluorouracil). Furthermore, both MTG and SRM exhibit high selectivity towards HCT 116 cell lines with selective indexes of 3.14 and 2.93 respectively compared to 5-FU (SI=0.60). Conclusions: These findings revealed that the medicinal and nutitional values of mitragynine obtained from ketum leaves that growth in tropical forest of Southeast Asia and its analogues does not limited to analgesic properties but could be promising antioxidant and anticancer or chemopreventive compounds.

• Korean Journal of Pharmacognosy
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• v.45 no.3
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• pp.194-199
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• 2014

The roots of Paeonia lactiflora (PL) has been traditionally used as analgesic, spasmolytic and tonic in Korea, China, and Japan. As part of a search for herbal medicine to treat diabetes and obesity, we confirmed hypoglycemic effect of PL through high fat diet-induced obese and diabetic mice experiments in vivo. Treatment of ethanolic extract from PL led to a significant decrease in glucose level, which is comparable to that of an antidiabetic drug metformin. In addition, PL selectively stimulates the transcriptional activities of both peroxisome proliferator-activated receptor $(PPAR){\alpha}$ and ${\gamma}$, and inhibits enzymatic activity of protein tyrosine phosphatase 1B (PTP1B), which are predicted to be therapeutic target in treatment of type2 diabetes and obesity. Especially, the n-hexane fraction (Hx) from PL ethanol extract showed more potent activities on $PPAR{\alpha}$ and than others and exihibited moderate inhibitory activity against PTP1B.

• Journal of the Korean Orthopaedic Association
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• v.55 no.1
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• pp.9-28
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• 2020

Non-steroidal anti-inflammatory drugs (NSAIDs) are the most commonly used drugs worldwide for chronic pain, such as arthritis, and there are many different types depending on their composition and mechanism. After long-term use, various side effects can occur, such as gastrointestinal and cardiovascular complications. With a similar analgesic effect to that of traditional non-selective NSAIDs, cyclooxygenase-2-selective NSAIDs have been highly anticipated, because they could complement gastrointestinal tolerance. On the other hand, because of concerns about cardiovascular safety in 2004 and 2005, and the license withdrawals of rofecoxib and valdecoxib, the interest in the side effects of NSAIDs is increasing. Therefore, it is important to use the necessary drugs at a minimum, considering the side effects and interactions of each drug. This study examined the side effects and characteristics of each NSAID that may occur and reviewed the recent research and guidelines related to the use of non-selective NSAIDs and cyclooxygenase-2-selective NSAIDs.

• The Korean Journal of Pain
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• v.27 no.4
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• pp.326-333
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• 2014

Background: Nefopam is a centrally acting non-opioid analgesic agent. Its analgesic properties may be related to the inhibitions of monoamine reuptake and the N-methyl-D-aspartate (NMDA) receptor. The antinociceptive effect of nefopam has been shown in animal models of acute and chronic pain and in humans. However, the effect of nefopam on diabetic neuropathic pain is unclear. Therefore, we investigated the preventive effect of nefopam on diabetic neuropathic pain induced by streptozotocin (STZ) in rats. Methods: Pretreatment with nefopam (30 mg/kg) was performed intraperitoneally 30 min prior to an intraperitoneal injection of STZ (60 mg/kg). Mechanical and cold allodynia were tested before, and 1 to 4 weeks after drug administration. Thermal hyperalgesia was also investigated. In addition, the transient receptor potential ankyrin 1 (TRPA1) and TRP melastatin 8 (TRPM8) expression levels in the dorsal root ganglion (DRG) were evaluated. Results: Pretreatment with nefopam significantly inhibited STZ-induced mechanical and cold allodynia, but not thermal hyperalgesia. The STZ injection increased TRPM8, but not TRPA1, expression levels in DRG neurons. Pretreatment with nefopam decreased STZ-induced TRPM8 expression levels in the DRG. Conclusions: These results demonstrate that a nefopam pretreatment has strong antiallodynic effects on STZ-induced diabetic rats, which may be associated with TRPM8 located in the DRG.

• Journal of Dental Anesthesia and Pain Medicine
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• v.16 no.4
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• pp.289-294
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• 2016

Background: Control of postoperative pain is an important aspect of postoperative patient management. Among the methods of postoperative pain control, patient-controlled analgesia (PCA) has been the most commonly used. This study tested the convenience and safety of a PCA method in which the dose adjusted according to time. Methods: This study included 100 patients who had previously undergone orthognathic surgery, discectomy, or total hip arthroplasty, and wished to control their postoperative pain through PCA. In the test group (n = 50), the rate of infusion was changed over time, while in the control group (n = 50), drugs were administered at a fixed rate. Patients' pain scores on the visual analogue scale, number of rescue analgesic infusions, side effects, and patients' satisfaction with analgesia were compared between the two groups. Results: The patients and controls were matched for age, gender, height, weight, and body mass index. No significant difference in the mount of drug administered was found between the test and control groups at 0-24 h after the operation; however, a significant difference was observed at 24-48 h after the operation between the two groups. No difference was found in the postoperative pain score, number of side effects, and patient satisfaction between the two groups. Conclusions: Patient-controlled anesthesia administered at changing rates of infusion has similar numbers of side effects as infusion performed at a fixed rate; however, the former allows for efficient and safe management of postoperative pain even in small doses.

• The Korean Journal of Pain
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• v.29 no.3
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• pp.153-157
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• 2016

Tapentadol is a novel oral analgesic with a dual mode of action as an agonist of the ${\mu}$-opioid receptor (MOR), and as a norepinephrine reuptake inhibitor (NRI) all in a single molecule. Immediate release (IR) tapentadol shows its analgesic effect quickly, at around 30 minutes. Its MOR agonistic action produces acute nociceptive pain relief; its role as an NRI brings about chronic neuropathic pain relief. Absorption is rapid, with a mean maximal serum concentration at 1.25-1.5 h after oral intake. It is present primarily in the form of conjugated metabolites after glucuronidation, and excretes rapidly and completely via the kidneys. The most common adverse reactions are nausea, dizziness, vomiting, and somnolence. Constipation is more common in use of the ER formulation. Precautions against concomitant use of central nervous system depressants, including sedatives, hypnotics, tranquilizers, general anesthetics, phenothiazines, other opioids, and alcohol, or use of tapentadol within 14 days of the cessation of monoamine oxidase inhibitors, are advised. The safety and efficacy have not been established for use during pregnancy, labor, and delivery, or for nursing mothers, pediatric patients less than 18 years of age, and cases of severe renal impairment and severe hepatic impairment. The major concerns for tapentadol are abuse, addiction, seeking behavior, withdrawal, and physical dependence. The presumed problem for use of tapentadol is to control the ratio of MOR agonist and NRI. In conclusion, tapentadol produces both nociceptive and neuropathic pain relief, but with worries about abuse and dependence.

• The Korean Journal of Pain
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• v.24 no.3
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• pp.131-136
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• 2011

Background: Pregabalin is an anticonvulsant and analgesic agent that interacts selectively with the voltage-sensitive-$Ca^{2+}$-channel alpha-2-delta subunit. The aim of this study was to evaluate whether the analgesic action of intrathecal (IT) pregabalin is associated with KATP channels in the rat formalin test. Methods: IT PE-10 catheters were implanted in male Sprague-Dawley rats (250.300 g) under inhalation anesthesia using enflurane. Nociceptive behavior was defined as the number of hind paw flinches during 60 min after formalin injection. Ten min before formalin injection, IT drug treatments were divided into 3 groups: normal saline (NS) $20\;{\mu}l$ (CON group); pregabalin 0.3, 1, 3 and $10\;{\mu}g$ in NS $10\;{\mu}l$ (PGB group); glibenclamide $100\;{\mu}g$ in DMSO $5\;{\mu}l$ with pregabalin 0.3, 1, 3 and $10\;{\mu}g$ in NS $5\;{\mu}l$ (GBC group). All the drugs were flushed with NS $10\;{\mu}l$. Immunohistochemistry for the $K_{ATP}$ channel was done with a different set of rats divided into naive, NS and PGB groups. Results: IT pregabalin dose-dependently decreased the flinching number only in phase 2 of formalin test. The log dose response curve of the GBC group shifted to the right with respect to that of the PGB group. Immunohistochemistry for the $K_{ATP}$ channel expression on the spinal cord dorsal horn showed no difference among the groups 1 hr after the formalin test. Conclusions: The antinociceptive effect of pregabalin in the rat formalin test was associated with the activation of the $K_{ATP}$ channel. However, pregabalin did not induce $K_{ATP}$ channel expression in the spinal cord dorsal horn.

• Journal of Dental Anesthesia and Pain Medicine
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• v.17 no.1
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• pp.47-53
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• 2017

Background: Every patient who undergoes mandibular third molar surgery is concerned about post-operative pain. Indeed, previous researchers have used various methods to treat such pain. This study aimed to assess the effectiveness of sublingual injection of dexamethasone (8 mg) to treat post-operative pain after mandibular third molar surgery. Method: This was a randomized, double-blind, split-mouth, clinical trial, involving 48 healthy patients who required surgical removal of two mandibular third molars with similar bilateral positions. All operations were performed by the same experienced surgeon. The patients were randomized into a study group (8 mg dexamethasone injection) and a placebo group (normal saline injection). Both interventions were injected into the sublingual space immediately after local anesthesia, 30 min before the first incision. The study group received an 8 mg dexamethasone injection, while the placebo group received a normal saline injection. The wash period between the patients' two operations was 3 to 4 weeks. Pain was assessed by recording the number of analgesic tablets (rescue drug) consumed, as well as by noting the patients' responses to the visual analog scale (VAS) on the first, second, and third days after surgery. Results: The study group differed significantly from the placebo group in terms of VAS score and analgesic consumption. Conclusion: Dexamethasone (8 mg), injected sublingually, significantly eased post-operative pain after surgical removal of the mandibular third molar.