• Journal of Ginseng Research
• /
• 제29권2호
• /
• pp.86-93
• /
• 2005

This study was undertaken to determine the antagonism of the ginseng total saponin (GTS) on the development of nalbuphine-induced tolerance and physical dependence. GTS is blown to have antinarcotic action with a dose of 100mg/kg (i.p.) in rats. STS significantly inhibits the development of nalbuphine-induced physical dependence as well as the tolerance. The level of pCREB was elevated in the striatum by the chronic treatment with nalbuphine or GTS, how-ever, the elevation of pCREB was inhibited by the GTS co-treatment. It has been suggested that NMDA receptor and/or NO is involved in the penomena of opioid dependence and withdrawal. However, the level of nNOS and NR1 was not modulated by the treatment with nalbuphine or GTS on the cortex, hippocampus and striatum in the rat brain. These results suggest that the GTS could be used to ameliorate the nalbuphine tolerance and withdrawal symptoms.

• 대한약학회:학술대회논문집
• /
• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
• /
• pp.111.1-111.1
• /
• 2002

• Biomolecules & Therapeutics
• /
• 제13권1호
• /
• pp.13-19
• /
• 2005

The study was undertaken to determine the antagonism of the AP1700 on the development of nalbuphine-induced tolerance and physical dependence. AP1700 is an oriental drug preparationcomposed of 5 natural products and is known to have antinarcotic action with an oral dose of 250 mg/kg in rats. AP1700 significantly inhibits the development of antinarcotic action with an oral dose of 250 mg/kg in rats. AP1700 significantly inhibits the development of nalbuphine-induced physical dependence but does not the tolerance. Mitogen-activated protein kinase, which include extracellular signal-regulated kinase (ERK), p38 and c-Jun N-terminal kinase (JNK)/stress-activated protein kinase (SAPK) play critical roles in cell growth and survival and drug abuse. The level of pCREB was elevated in the hippocampus by the chronic treatment with nalbuphine, however, the elevation of pCREB was not inhibited by the AP1700 co-treatment. Interestingly, the level of pERK was decreased in the co-treatment with nalbuphine and AP1700 on the cortex and striatum. However, the level of nNOS and NR1 was not modulated by the treatment with nalbuphine or AP1700 on the cortex, hippocampus and striatum in the rat brain. These results suggest that the AP1700 could be used to ameliorate the nalbuphine withdrawal symptoms.

• 대한불안의학회지
• /
• 제1권1호
• /
• pp.37-42
• /
• 2005

Benzodiazepines are widely used for a variety of conditions in psychiatric field. In this article, the author reviewed the indications, the effects on anxiety and sleep disorders, the side effects, the drug-drug interactions, and the tapering strategies. Benzodiazepines were relatively safe and useful for the treatment of anxiety and sleep disorders. However, used clinically, benzodiazepines can induce many adverse effects (e. g. over-sedation, cognitive impairments, paradoxical effects, dependence and withdrawal symptoms, and so on). Currently available informations about their effects on the developing fetus is controversial. For this reason, pregnant women and nursing mother should be cautioned against the use of benzodiazepines. Drug-drug interactions have to be considered in combination treatments. For the tapering issues, gradual tapering was important to prevent the withdrawal symptoms. Especially, the tapering schedules have to be individualized for the each long-term benzodiapzepine users.

• 한국응용약물학회:학술대회논문집
• /
• 한국응용약물학회 2004년도 Annual Meeting of the Korean Society ofApplied Pharmacology
• /
• pp.140-144
• /
• 2004

• 약학회지
• /
• 제34권6호
• /
• pp.415-421
• /
• 1990

The effects of temperature, pH, light and concentration on the degradation of trimebutine maleate in aqueous solution were investigated on the basis of accelerated stability analysis, and the stabilization of the solution was attempted by addition of several additives. The decomposition of trimebutine maleate in solution followed first-order reaction the was not only accelerated by temperature elevation but also the lower the concentratin the more speeded up the reaction. The decomposition mechanism of trimebtine could be confirmed by hydrolysis of ester bond in the structure. It was assumed trimebutine maleate is so photosensitive that the solution of the drug underwent accelerated decomposition under UV rays. What is more, the degradation of trimebutine solution was supposed to catalyzed by specific acid-base catalysis considered the pH dependence for the hydrolysis of ester, and the solution was most stable over the range of pH 2-2.8 in solution. The additives, citric acid, asparitc acid and glutamic acid, inhibited considerably the decomposition of the drug solution, and these additives might be used as stabilizers in trimebutine maleate solution.

• The Korean Journal of Physiology and Pharmacology
• /
• 제26권5호
• /
• pp.397-404
• /
• 2022

Fesoterodine, an antimuscarinic drug, is widely used to treat overactive bladder syndrome. However, there is little information about its effects on vascular K⁺ channels. In this study, voltage-dependent K⁺ (Kv) channel inhibition by fesoterodine was investigated using the patch-clamp technique in rabbit coronary artery. In whole-cell patches, the addition of fesoterodine to the bath inhibited the Kv currents in a concentration-dependent manner, with an IC₅₀ value of 3.19 ± 0.91 μM and a Hill coefficient of 0.56 ± 0.03. Although the drug did not alter the voltage-dependence of steady-state activation, it shifted the steady-state inactivation curve to a more negative potential, suggesting that fesoterodine affects the voltage-sensor of the Kv channel. Inhibition by fesoterodine was significantly enhanced by repetitive train pulses (1 or 2 Hz). Furthermore, it significantly increased the recovery time constant from inactivation, suggesting that the Kv channel inhibition by fesoterodine is use (state)-dependent. Its inhibitory effect disappeared by pretreatment with a Kv 1.5 inhibitor. However, pretreatment with Kv2.1 or Kv7 inhibitors did not affect the inhibitory effects on Kv channels. Based on these results, we conclude that fesoterodine inhibits vascular Kv channels (mainly the Kv1.5 subtype) in a concentration- and use (state)-dependent manner, independent of muscarinic receptor antagonism.

• Journal of Radiation Protection and Research
• /
• 제31권4호
• /
• pp.181-186
• /
• 2006

본 연구에서는 최근 들어 새롭게 소개되고 있는 유리선량계의 재현성 및 선량의 선형성 그리고 에너지 의존성을 조사하였다. 50개의 유리선량계를 5번 판독한 결과, 재현성은 모두 ${\pm}1.2%$(1SD)이내에서 잘 일치하는 것을 알 수 있었으며 $^{60}Co$ 감마선에서 선량 0.5 Gy부터 50 Gy까지 유리선량계의 반응도를 평가해 본 결과는 0.9998의 선형계수를 확인할 수 있었다. 또한 유리선량계의 에너지의존성은 원통형의 전리함으로 측정한 선량과 비교했을 때 광자선에너지 6, 15 MV 각각에 대해 $^{60}Co$ 감마선의 반응도로 일반화시킨 결과 모두 ${\pm}1.5%$(1SD)이내에서 일치하였다. 이는 고에너지 광자선에 대해 열형광선량계와는 비슷한 결과이며 다이오드 선량계와 비교해서 했을 때는 낮은 에너지 의존성을 가지는 것이다. 따라서 유리선량계는 기존의 다른 선량계에 비해 사용 가능한 선량범위가 넓고 고에너지 광자선에서 에너지의존성이 낮으며 유효크기가 작은 장점 등으로 인해 소조사면의 고선량을 사용하는 방사선 수술분야의 선량측정에 적합한 선량계라는 것을 확인할 수 있었다.

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권7호
• /
• pp.3293-3297
• /
• 2014

Background: Pine needle oil from crude extract of pine needles has anti-tumor effects, but the effective component is not known. Methods: In the present study, compounds from a steam distillation extract of pine needles were isolated and characterized. Alpha-pinene was identified as an active anti-proliferative compound on hepatoma carcinoma BEL-7402 cells using the MTT assay. Results: Further experiments showed that ${\alpha}$-pinene inhibited BEL-7402 cells by arresting cell growth in the G2/M phase of the cell cycle, downregulating Cdc25C mRNA and protein expression, and reducing cycle dependence on kinase 1(CDK1) activity. Conclusion: Taken together, these findings indicate that ${\alpha}$-pinene may be useful as a potential anti-tumor drug.

• Journal of Pharmaceutical Investigation
• /
• 제24권3호
• /
• pp.155-165
• /
• 1994

Some mucoadhesive polymers such as hydroxypropylcelluose (HPC) and carbopol-934 (CP) have been employed for the preparation of mucoadhesive polymeric systems, and their physical properties including mucoadhesion, swelling, and drug release were evaluated. A new simple experimental technique that can quantitatively measure the bioadhesive properties of various polymeric systems has been developed by the methods of detachment force test. As the polymeric systems, the discs of freeze-dried HPC/CP solid dispersions were prepared. The mucosa used in these tests were upper, middle, and lower parts of small intestine of male rats weighing $300{\sim}350\;g$. Detachment forces were increased as the mole fraction of CP increased in discs of HPC/CP solid dispersions. In the points of intestinal site dependence of mucoadhesion, the solid dispersions revealed non-specific mucoadhesion to the intestine. Swelling and drug release characteristics of mucoadhesive polymeric systems were studied extensively to find out the feasibility for the oral controlled delivery systems. Swelling ratio, expressed as the final height/initial height, has been determined in various pH buffer solutions. Hydrochlorothiazide (HCT) was employed as a model drug for release study. Apparent swelling and drug release rate constants, $K_s$ and $K_r$ respectively, were obtained from the square-root time plot of either swelling ratio or released amount of drug, particularly for the time periods before reaching the equilibrium. As a result, the swelling ratio of HPC/CP solid dispersions was increased as the weight percentage of CP increased. Similarly, the release of HCT from the solid dispersions was dependent on pH changes and CP contents, resulted in the slower release of HCT with the increases of pH and CP contents.