• Biomolecules & Therapeutics
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• v.19 no.1
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• pp.45-51
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• 2011

These experiments were designed to use typical makers from behaviors and molecular basis in addicted animals of morphine and cocaine. Morphine has been widely abused with a high physical dependence liability. Morphine withdrawal activates the intracellular cAMP signaling pathway and further leads to changes in the expression of the cAMP response element binding protein (CREB), which may be important to the development and expression of morphine dependence. From these experiments, repeated morphine (10 mg/kg, twice per day for 7 days) developed physical dependence. Withdrawal signs were precipitated by naloxone and also increased the expression of the CREB. In addition, repeated exposure of cocaine (15 mg/kg) to mice develops locomotor sensitization and produced lasting behavioral sensitivity. Cocaine- and amphetamine-regulated transcript peptide (CART) peptide was up-regulated by repeated administration of cocaine in the striatum. Therefore, repeated morphine induced the development of physical dependence and increased pCREB. In addition, repeated cocaine induced locomotor sensitization and over-expressed CART peptide. In conclusion, the development of physical dependence and pCREB for morphine, and locomotor sensitization and CART peptide over-expression for cocaine would be useful markers to predict the abuse potential of opioid analgesics and pychostimulant drugs in animals, respectively.

• Bulletin of the Korean Chemical Society
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• v.34 no.6
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• pp.1800-1808
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• 2013

Dual-responsive amphiphilic block copolymers were synthesized by combining enzymatic ring-opening polymerization (eROP) of ${\varepsilon}$-caprolactone (CL) and ATRP of N,N-dimethylamino-2-ethyl methacrylate (DMAEMA). The obtained block copolymers were characterized by gel permeation chromatography (GPC), $^1H$ NMR and FTIR-IR. The critical micelle concentration (CMC) of copolymer was determined by fluorescence spectra, it can be found that with hydrophilic block (PDMAEMA) increasing, CMC value of the polymer sample increased accordingly, and the CMC value was 0.012 mg/mL, 0.025 mg/mL and 0.037 mg/mL for $PCL_{50}$-b-$PDMAEMA_{68}$, $PCL_{50}$-b-$PDMAEMA_{89}$, $PCL_{50}$-b-$PDMAEMA_{112}$, $PCL_{50}$-b-$PDMAEMA_{89}$ was chosen as drug carrier to study in vitro release profile of anti-cancer drug (taxol). The temperature and pH dependence of the values of hydrodynamic diameter (Dh) of micelles, and self-assembly of the resulting block copolymers in water were evaluated by dynamic light scattering (DLS). The result showed that with the temperature increasing and pH decreasing, the Dh decreased. Drug-loaded nanoparticles were fabricated using paclitaxel as model. Transmission electron microscopy (TEM) and atomic force microscopy (AFM) had been explored to study the morphology of the hollow micelles and the nanoparticles, revealing well-dispersed spheres with the average diameters both around 80 nm. In vitro release kinetics of paclitaxel from the nanoparticles was also investigated in different conditions (pH and temperature, etc.), revealing that the drug release was triggered by temperature changes upon the lower critical solution temperature (LCST) at pH 7.4, and at $37^{\circ}C$ by an increase of pH.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1994.04a
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• pp.50-62
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• 1994

Opium, morphine and rotated natural and synthetic opiates have been used since antiquity, and to the present, for the relief of moderate and severe pain. Morphine and pharmacologically related drugs, however, produced an array of undesired or dangerous side effect that limit their use as analgesics. Prominent among the limiting side effects are constipation, respiratory depression, release of prolactin, and liability for the production of drug dependence. It was our aim to develop, if possible, a drug or class of drugs with analgesic activity similar to that of morphine, but without the serious side effects associated with morphine. Our overall strategy was to take advantage of advancing knowledge concerning multiple types of opioid receptors, to develop ligands selective for the delta type receptors, to determine whether delta receptor agonists offer advantages over mu agonists, then to design compounds with pharmacokinetic properties compatible with practical therapeutic application. All but the last of these objectives have been realized.

• Archives of Pharmacal Research
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• v.12 no.4
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• pp.239-242
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• 1989

Several physiological components containing a secondary amino group were capable of reacting sodium nitroprusside to form potentially carcinogenic nitrosamines under physiological conditions (pH 7.3, 37). In each case the products were identical to those produced upon reaction with nitrous acid at much lower pH values. Reaction rates measured with proline were shown to reflect a first order dependence on both amine and nitroprusside concentrations. The strong influences of pH on the reactions of sodium nitro prusside with amines were also observed. These results show sodium nitroprusside could be a very potent nitrosation agent under physiological conditions.

• Journal of The Korean Society of Clinical Toxicology
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• v.1 no.1
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• pp.21-26
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• 2003

Methamphetamine (MA) is a major drug of abuse in Korea. Currently preliminary evidence suggests that MA dependence may cause long-term neural damage in human. Repeated exposure to psychostimulants such as methamphetamine results in behavioral sensitization, a paradigm thought to be relevant to drug craving and addiction in human. Sensitization alters neural circuitry involved in normal processes of incentrive, motivation, and reward. However the precise mechanism of this behavioral sensitization has not yet been fully elucidated. Repeated use of high dose MA causes neurotoxicity which is characterized by a long-lasting depletion of striatal dopamine (DA) and tyrosin hydroxylase activity of DA, DA-transporter binding sites in the striatum. The loss of DA transporters correlates with memory problems and lack of motor coordination. DA fuels motivation and pleasure, but it' s also crucial for learning and movement. This selective review provides a summary of studies that assess the neurobiological mechanisms of MA.

• The Korean Journal of Physiology and Pharmacology
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• v.27 no.1
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• pp.95-103
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• 2023

Rosiglitazone is a thiazolidinedione-class antidiabetic drug that reduces blood glucose and glycated hemoglobin levels. We here investigated the interaction of rosiglitazone with Kv3.1 expressed in Chinese hamster ovary cells using the wholecell patch-clamp technique. Rosiglitazone rapidly and reversibly inhibited Kv3.1 currents in a concentration-dependent manner (IC₅₀ = 29.8 µM) and accelerated the decay of Kv3.1 currents without modifying the activation kinetics. The rosiglitazonemediated inhibition of Kv3.1 channels increased steeply in a sigmoidal pattern over the voltage range of -20 to +30 mV, whereas it was voltage-independent in the voltage range above +30 mV, where the channels were fully activated. The deactivation of Kv3.1 current, measured along with tail currents, was also slowed by the drug. In addition, the steady-state inactivation curve of Kv3.1 by rosiglitazone shifts to a negative potential without significant change in the slope value. All the results with the use dependence of the rosiglitazone-mediated blockade suggest that rosiglitazone acts on Kv3.1 channels as an open channel blocker.

• Journal of Pharmaceutical Investigation
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• v.37 no.4
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• pp.229-235
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• 2007

Multi-layered granules were prepared by a fluidized-bed coater and uniformed granules were obtained with a size range between $950{\sim}1000{\mu}m$ in diameter. The granule system was composed of three layers, i.e. seed layer with sugar sphere bead and a water-swellable polymer, middle layer with a drug, solubilizer and polymer, and the top layer of porous membrane with a polymeric binder. The aim of this work is to find out the dependence of a drug dissolution rate on the amount of a water-soluble binder and a solubilizer in the granule system. The results showed that the higher amount of hydrophilic binder in the porous membrane, gave the bigger pore size and porosity and made faster dissolution rate and also the higher amount of solubilizer in drug layer enhanced the dissolution rate of drug.

• Archives of Pharmacal Research
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• v.26 no.7
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• pp.540-544
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• 2003

Morphine, an analgesic with significant abuse potential, is considered addictive because of drug craving and psychological dependence. It is reported that repeated treatment of morphine can produce conditioned place preference (CPP) showing a reinforcing effect in mice. CPP is a useful method for the screening of morphine-induced psychological dependence. In the present study, we investigated the effect of the methanolic extract of Coptis japonica (MCJ) on morphine-induced CPP in mice. Furthermore, we examined c-fos expression in the parietal cortex, piriform cortex, striatum, nucleus accumbens, and hippocampus of the morphine-induced CPP mouse brain. Treatment of MCJ 100 mg/kg inhibited morphine-induced CPP. Expression of c-fos was increased in the cortex, striatum, nucleus accumbens, and hippocampus of the morphine-induced CPP mouse brain. These increases of expression were inhibited by treatment with MCJ 100 mg/kg, compared to the morphine control group. Taken together, these results suggest that MCJ inhibits morphine-induced CPP through the regulation of c-fos expression in the mouse brain.

• Biomolecules & Therapeutics
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• v.16 no.2
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• pp.113-117
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• 2008

Morphine is a potent analgesic with significant abuse potential, because of drug craving and psychological dependence. It is reported that repeated treatment of morphine can produce conditioned place preference (CPP) showing a reinforcing effect in mice. Previously, we have reported the inhibitory effect of the methanolic extract of Coptis japonica (MCJ) on morphine-induced CPP in mice. The present study was employed whether p-CREB expression is involved in the inhibitory effect of MCJ on the morphine-induced CPP in the mouse hippocampus. Repeated administration of MCJ 100 mg/kg inhibited morphine-induced CPP. Expression of p-CREB was increased in the dentate gyrus of the hippocampus that had undergone morphineinduced CPP. This increase of expression was significantly inhibited by administration of MCJ 100 mg/kg, compared to the morphine control group. Taken together, these results suggest that MCJ inhibits morphine-induced CPP through the regulation of p-CREB expression in the mouse dentate gyrus of the hippocampus.

• Macromolecular Research
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• v.17 no.2
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• pp.72-78
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• 2009

Size control of therapeutic carriers in drug delivery systems has become important due to its relevance to biodistribution in the human body and therapeutic efficacy. To understand the dependence of particle size on the formation condition during nanoprecipitation method, we prepared nanoparticles from biodegradable, amphiphilic block copolymers and investigated the particle size and structure of the resultant nanoparticles according to various process parameters. We synthesized monomethoxy poly(ethylene glycol)-poly($\varepsilon$-caprolactone) block copolymer, MPEG-PCL, with different MPEG/PCL ratios via ring opening polymerization initiated from the hydroxyl end group of MPEG. Using various formulations with systematic change of the block ratio of MPEG and PCL, solvent choice, and concentration of organic phase, MPEG-PCL nanoparticles were prepared through nanoprecipitation technique. The results indicated that (i) the nanoparticles have a dual structure with an MPEG shell and a PCL core, originating from self-assembly of MPEG-PCL copolymer in aqueous condition, and (ii) the size of nanoparticles is dependent upon two sequential processes: diffusion between the organic and aqueous phases and solidification of the polymer.