• Proceedings of the Korean Society of Applied Pharmacology
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• 1996.04a
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• pp.220-220
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• 1996

The objectives of this study were to evaluate the pharmacokinetics of SJ-151 which is a new NSAID in male Beagle dogs following a single oral dosing. Seven beagle dogs (10-l2kg) were all administered a single oral gavage(10mg/kg) of SJ-151 tablet and serial blood samples of approximately 5$m\ell$ were then drawn from the cephalic vein of each animal at 0(predose), 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24hours postdosc. SJ-151 (Cinmetacinㆍbutendiol)and cimetacin were quantified in the plasma fraction by HPLC assay. The pharmacokinetic parameters calculated from the plasma concentrations of SJ-151 in dayl are Cmax(ng/$m\ell$)509$\pm$248, Tmax(hr) 1.50$\pm$0.45, AUC(ng.hr/$m\ell$) 1,750$\pm$762, tl/2$\alpha$ 0.98$\pm$0.30, t1/2$\beta$ 12.0$\pm$6.75. The pharmacokinetic parameters calculated from the plasma concentrations of Cinmetacin in day 1 are Cmax(ng/$m\ell$)258$\pm$74.1, Tmax(hr)2.42$\pm$ 0.92, AUC(ng.hr/$m\ell$) 1,820$\pm$318, t1/2$\alpha$ 1.74$\pm$0.49, t1/2$\beta$ 25.4$\pm$13.4.

• Biomolecules & Therapeutics
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• v.23 no.6
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• pp.590-596
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• 2015

The emergence and use of synthetic cannabinoids have greatly increased in recent years. These substances are easily dispensed over the internet and on the streets. Some synthetic cannabinoids were shown to have abuse liability and were subsequently regulated by authorities. However, there are compounds that are still not regulated probably due to the lack of abuse liability studies. In the present study, we assessed the abuse liability of three synthetic cannabinoids, namely JWH-030, JWH-175, and JWH-176. The abuse liability of these drugs was evaluated in two of the most widely used animal models for assessing the abuse potential of drugs, the conditioned place preference (CPP) and self-administration (SA) test. In addition, the open-field test was utilized to assess the effects of repeated (7 days) treatment and abrupt cessation of these drugs on the psychomotor activity of animals. Results showed that JWH-175 (0.5 mg/kg), but not JWH-030 or JWH-176 at any dose, significantly decreased the locomotor activity of mice. This alteration in locomotor activity was only evident during acute exposure to the drug and was not observed during repeated treatment and abstinence. Similarly, only JWH-175 (0.1 mg/kg) produced significant CPP in rats. On the other hand, none of the drugs tested was self-administered by rats. Taken together, the present results indicate that JWH-175, but not JWH-030 and JWH-176, may have abuse potential. More importantly, our findings indicate the complex psychopharmacological effects of synthetic cannabinoids and the need to closely monitor the production, dispensation, and use of these substances.

• The Korean Journal of Physiology and Pharmacology
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• v.14 no.6
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• pp.435-440
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• 2010

Valproic acid (VPA) is a well-known anti-epileptic and mood stabilizing drug. A growing number of reports demonstrate that VPA is neuroprotective against various insults. Despite intensive efforts to develop new therapeutics for stroke over the past two decades, all treatments have thus far failed to show clinical effect because of treatment-limiting side effects of the drugs. Therefore, a safety-validated drug like VPA would be an attractive candidate if it has neuroprotective effects against ischemic insults. The present study was undertaken to examine whether pre- and post-insult treatments with VPA protect against brain infarct and neurological deficits in mouse transient (tMCAO) and permanent middle cerebral artery occlusion (pMCAO) models. In the tMCAO (2 hr MCAO and 22 hr reperfusion) model, intraperitoneal injection of VPA (300 mg/kg, Lp.) 30 min prior to MCAO significantly reduced the infarct size and the neurological deficit. VPA treatment immediately after reperfusion significantly reduced the infarct size. The administration of VPA at 4 hr after reperfusion failed to reduce the infarct size and the neurological deficit. In the pM CAO model, treatment with VPA (300 mg/kg, i.p.) 30 min prior to MCAO significantly attenuated the infarct size, but did not affect the neurological deficit. Western blot analysis of acetylated H3 and H4 protein levels in extracts from the ischemic cortical area showed that treatment with VPA increased the expression of acetylated H3 and H4 at 2 hrs after MCAO. These results demonstrated that treatment with VPA prior to ischemia attenuated ischemic brain damage in both mice tMCAO and pMCAO models and treatment with VPA immediately after reperfusion reduced the infarct area in the tMCAO model. VPA could therefore be evaluated for clinical use in stroke patients.

• The Korean Journal of Physiology and Pharmacology
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• v.19 no.6
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• pp.549-555
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• 2015

We attempted to investigate molecular mechanisms underlying phenotypic change of vascular smooth muscle cells (VSMCs) by determining signaling molecules involved in chemokine production. Treatment of human aortic smooth muscle cells (HAoSMCs) with thrombin resulted not only in elevated transcription of the (C-C motif) ligand 11 (CCL11) gene but also in enhanced secretion of CCL11 protein. Co-treatment of HAoSMCs with GF109230X, an inhibitor of protein kinase C, or GW5074, an inhibitor of Raf-1 kinase, caused inhibition of ERK1/2 phosphorylation and significantly attenuated expression of CCL11 at transcriptional and protein levels induced by thrombin. Both Akt phosphorylation and CCL11 expression induced by thrombin were attenuated in the presence of pertussis toxin (PTX), an inhibitor of Gi protein-coupled receptor, or LY294002, a PI3K inhibitor. In addition, thrombin-induced production of CCL11 was significantly attenuated by pharmacological inhibition of Akt or MEK which phosphorylates ERK1/2. These results indicate that thrombin is likely to promote expression of CCL11 via PKC/Raf-1/ERK1/2 and PTX-sensitive protease-activated receptors /PI3K/Akt pathways in HAoSMCs. We propose that multiple signaling pathways are involved in change of VSMCs to a secretory phenotype.

• The Korean Journal of Physiology and Pharmacology
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• v.16 no.6
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• pp.447-453
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• 2012

TLR6 forms a heterodimer with TLR2 and TLR4. While proinflammatory roles of TLR2 and TLR4 are well documented, the role of TLR6 in inflammation is poorly understood. In order to understand mechanisms of action of TLR6 in inflammatory responses, we investigated the effects of FSL-1, the TLR6 ligand, on expression of chemokine CCL2 and cytokine IL-$1{\beta}$ and determined cellular factors involved in FSL-1-mediated expression of CCL2 and IL-$1{\beta}$ in mononuclear cells. Exposure of human monocytic leukemia THP-1 cells to FSL-1 resulted not only in enhanced secretion of CCL2 and IL-$1{\beta}$, but also profound induction of their gene transcripts. Expression of CCL2 was abrogated by treatment with OxPAPC, a TLR-2/4 inhibitor, while treatment with OxPAPC resulted in partially inhibited expression of IL-$1{\beta}$. Treatment with FSL-1 resulted in enhanced phosphorylation of Akt and mitogen-activated protein kinases and activation of protein kinase C. Treatment with pharmacological inhibitors, including SB202190, SP6001250, U0126, Akt inhibitor IV, LY294002, GF109203X, and RO318220 resulted in significantly attenuated FSL-1-mediated upregulation of CCL2 and IL-$1{\beta}$. Our results indicate that activation of TLR6 will trigger inflammatory responses by upregulating expression of CCL2 and IL-$1{\beta}$ via TLR-2/4, protein kinase C, PI3K-Akt, and mitogen-activated protein kinases.

• Journal of Dental Anesthesia and Pain Medicine
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• v.20 no.1
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• pp.19-27
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• 2020

Background: Surgical extraction of third molars is associated with postoperative pain and swelling at the extraction site. Pain is commonly managed using non-steroidal anti-inflammatory drugs (NSAIDs). Postoperative pain is usually moderate to severe in the first 12 h postoperatively and lasts for 3-5 days. However, with NSAIDs, these symptoms usually subside within 24 h. Diclofenac sodium and etodolac are NSAIDs, more selectively cyclooxygenase-2 inhibitors, with good analgesic efficacies. Methods: We compared the safety and analgesic efficacy of diclofenac sodium with etodolac peroral after surgical extraction of third molars in a double-blind, double-dummy, parallel-group study. The subjective pain improvement and pain relief after 2, 6, 24, 48, and 72 h using the visual analogue scale were measured as the study outcome. Results: Etodolac was equivalent to diclofenac sodium in pain alleviation at all postoperative time periods. No significant differences were found between diclofenac sodium and etodolac groups (P > 0.05). Both study medications were well tolerated and safe with mild adverse effects in only a few participants. Conclusion: Diclofenac sodium and etodolac are comparable in terms of analgesic efficacy and safety after surgical removal of third molars.

• Biomolecules & Therapeutics
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• v.9 no.1
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• pp.63-68
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• 2001

General pharmacological properties of (R)-JG-381 were examined in laboratory animals to investigate its safety profile. Administration of (R)-JG-381 (50 and 100 mg/kg) in mice and rats had no effects of general behaviors, central nervous system of the animals in test systems of pentobarbital-induced sleeping time, writhing syndromes induced by 0.7% acetic acid, chemo-shock produced by pentylenetetrazole, and, however, had mild effects on motor coordination. Heart rate and blood pressure were not changed by (R)-JG-381 treatment. (R)-JG-381 also showed mild effects on intestinal propulsion and gastric secretion. These results suggest that (R)-JG-381 dose not exert serious pharmacological effects.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.432-432
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• 2002

Drug used in hospital is allowed marketing through after pharmacological and toxicological tests using various animals and clinical test of human in developing state. But as pre-marketing clinical study take short period with relatively a few of patients and strict selection criteria of people, pediatric, geriatric. pregnancy, liver and kidney patients may be excluded. As the safety of drug isn't completely evaluated before launching. it is important to collect and evaluate drug adverse reaction newly reported by medical practitioners and pharmacists. (omitted)

• Korean Journal of Pharmacognosy
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• v.33 no.2 s.129
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• pp.151-155
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• 2002

Previously, we have reported that the butanol fraction of the head of Panax ginseng had significant gastroprotective activity on gastritis and gastric ulcer models of rats. Considering the safety of the fraction for development of new anti-ulcerative agent or food supplement, general pharmacological study was carried on. The fraction was revealed that have no influence on spontaneous activity, phenobarbital-induced sleeping time, rotarod test, body temperature, gastro-intestinal motility, respiration and blood pressure. The fraction showed weak analgesic action in writhing syndrome and did not show any sign of acute toxicity in mice.

• Biomolecules & Therapeutics
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• v.1 no.2
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• pp.137-142
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• 1993

The possible tumor-promoting activities of sodium chloride (NaCl) and dimethyl itaconate (DMI), one of the quinone reductase inducers, were examined on stomach of male Wistar rats treated with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Administrations of NaCl and DMI after the initiation by MNNG resulted in various sized masses in the rat forestomach. Histopathologic studies showed that the combination of NaCl and DMI made an enhancing effect on the MNNG-induced carcinogenesis, resulting in papilloma in 5 weeks and squamous cell carcinoma in 20 weeks in submucosal area of forestomach. We also used an in vivo shortterm method for evaluating possible tumor-promoting activity with ornithine decarboxylase (ODC) as a marker. The markable inductions of the ODC activities by MNNG, NaCl, and DMI were found in the pyloric mucosa of rat stomach in time-dependent manners. A single administration of MNNG induced ODC activity up to 288 pmol $CO_2$/hr/mg protein at 24 hr after the administration. NaCl caused induction of ODC with a maximum of 179 pmol $CO_2$/hr/mg protein at 8 hr after the administration. ODC was induced up to 539 pmol $CO_2$/hr/mg protein at 16 hr after the administration of DMI. Additional treatment of NaCl and NaCl plus DMl caused 2 fold and 7 fold increases, respectively, in the ODC activity of the MNNG-alone group at 24 hr after the administration. These results suggest that NaCl and DMI have promoting activities in the rat gastric carcinogenesis initiated by MNNG.