• Proceedings of the PSK Conference
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• 2003.10b
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• pp.189.1-189.1
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• 2003

4-(4-Methoxyphenyl)-2-aminothiazole and 3-(4-methoxyphenyl)-5-aminothiadiazole derivatives have been synthesized and evaluated as selective antagonists for human adenosine A$_3$ receptors. A methoxy group in the 4-position of the phenyl ring and N-acetyl or propionyl substitutions of the aminothiazole and aminothiadiazole templates displayed great increases of binding affinity and selectivity for human adenosine A$_3$ receptors. The most potent A$_3$ antagonist of the present series, N-［3-(4-methoxy-phenyl)-［1,2,4］thiadiazol-5-yl］-acetamide exhibiting a K$\_$i/ value of 0.79 nM at human adenosine A$_3$ receptors, showed antagonistic property in functional assay of cAMP biosynthesis involved in one of the signal transduction pathways of adenosine A$_3$ receptors. (omitted)

• The Korean Journal of Food And Nutrition
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• v.30 no.6
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• pp.1364-1369
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• 2017

There is a growing demand for natural sleep aids due to various side effects of long-term administration of pharmacological treatments for insomnia. Honey has been reported to exhibit numerous potential health benefits, and it is hypothesized that honey may favorably affect insomnia treatment. Therefore, this study was performed to investigate the possible hypnotic effect of clover honey (CH) and to determine its in vivo mechanism. The total flavonoid content (TFC) of CH and fractions extracted with ethylacetate (EtOAc) and $H_2O$ was measured. The pentobarbital-induced sleep test using $GABA_A$-benzodiazepine (BZD) agonists and antagonists was conducted to evaluate the potential mechanism of action behind the sedative-hypnotic activity of CH in mice. The results showed that administration of 500 and 1,000 mg/kg of CH significantly (p<0.01) reduced the sleep latency to a level similar to that of diazepam (DZP, 2 mg/kg), and 1,000 mg/kg of CH significantly (p<0.01) prolonged the sleep duration, which was comparable to that of DZP (2 mg/kg). Administration of the EtOAc fraction with a higher TFC significantly reduced the sleep latency at 50 to 200 mg/kg and prolonged the sleep duration at 100 to 200 mg/kg, which were comparable to those after administration of DZP (2 mg/kg). However, co-administration of CH and EtOAc with flumazenil, a specific $GABA_A-BZD$ receptor antagonist, blocked the hypnotic effect. Our findings suggest that the hypnotic activity of CH may be attributed to allosteric modulation of $GABA_A-BZD$ receptors. The TFC of CH is expected to be a key factor that contributes to its hypnotic effect.

• Journal of Korean Neurosurgical Society
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• v.39 no.2
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• pp.130-135
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• 2006

Objective : After ischemic stroke, partial recovery of function frequently occurs and may depend on the plasticity of axonal connections. Here, we examine whether blockade of the Nogo/NogoReceptor[NgR] pathway might enhance axonal sprouting and thereby recovery after focal brain infarction. Methods : Adult male Sprague Dawley rats weighing $250{\sim}350g$ were used. Left middle cerebral artery occlusion[MCAO] was induced with a intraluminal filament. An osmotic mini pump [Alzet 2ML4, Alza Scientific Products, Palo Alto, CA] for the infusion of NgR-Ecto[310]-Fc to block Nogo/NgR pathway was implanted 1 week after cerebral ischemia. Prior to induction of ischemia, all animals received training in the staircase and rotarod test. Two weeks after biotin dextran amine injection, animals were perfused transcardially with PBS, followed by 4% paraformadehyde/PBS solution. Brain and cervical spinal cord were dissected. Eight coronal sections spaced at 1mm intervals throughout the forebrain of each animal with cresyl violet acetate for determination of infarction size. Images of each section were digitized and the infarct area per section was measured with image analysis software. Results : Histological examination at 11 weeks post-MCAO demonstrates reproducible stroke lesions and no significant difference in the size of the stroke between the NgR[310]Ecto-Fc protein treated group and the control group. Behavioral recovery is significantly better and more rapid in the NgR-Ecto[310]-Fe treated group. Blockade of NgR enhances axonal sprouting from the uninjured cerebral cortex and improves the return of motor task performance. Conclusion : Pharmacological interruption of NgR allows a greater degree of axonal plasticity in response this is associated with improved functional recovery of complicated motor tasks.

• Journal of Yeungnam Medical Science
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• v.8 no.2
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• pp.95-105
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• 1991

This study was designed to investigate the effect of GABA and related substances on the spontaneous contraction of rat small intestine. The rats(Sprague-Dawley), weighing 200-250g, were sacrificed by cervical dislocation, and the small intestine was isolated. Longitudinal muscle strips from duodenum, jejunum and ileum were suspended in Biancani's isolated muscle chambers and myographied isometrically. GABA and muscimol, a GABA A receptor agonist relaxed the duodenum and jejunum significantly, but baclofen-induced relaxation in those muscle strips was negligible. The effectiveness of GABA and muscimol in various regions were the greatest on duodenum, and greater on jejunum than on ileum The effect of GABA and muscimol was antagonized by bicuculline, a compeptitive GABA A receptor antagonist and picrotoxin, a noncomptitive GABA A receptor antagonist. Duodenal relaxation induced by GABA and muscimol was unaffected by hexamethonium, but was prevented by tetrodotoxin. These results suggest that GABA inhibit the contractility of smooth muscle with distinct regional difference of efficacy, and the site of inhibitory action is the GABA A receptor existing at the presynaptic membrane of postganglionic excitatory nerves.

• Journal of Acupuncture Research
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• v.22 no.2
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• pp.19-32
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• 2005

Objectives : to evaluate the analgesic effect of bee venom acupuncture on Choksamni (ST36) in the collagen-induced arthritis rats and investigate the role played by serotonergic receptor subtypes (5-HT1a, 5-HT2a) in the antinociceptive effect of bee venom acupuncture in a thermal hyperalgesia test Methods : Experiments were performed on 5 week-aged 60 male Sprague-Dawley rats according to National Institute of Health guidelines and the ethical guidelines of the International Association for the Study of Pain (IASP). Arthritis was induced with arthrogenic collagen emulsion (Bovine type II collagen ${\mu}g$ with incomplete Freund's adjuvant $100\;{\mu}g$). The onset of arthritis was considered to be present when erythema and swelling were detected in at least one joint. The thermal hyperalgesia was evaluated weekly with tail flick test in the rats of severity grade 3 without any injury at tail and foot (including inflammation, ulceration, snap). In the fourth week after first immunization, the analgesic effect of bee venom acupuncture (Choksamni, ST36) was measured with consecutive tail flick latency after intraperitoneal injection of spiroxatrine (1mg/kg) and spiperone (1mg/kg). Results : Chronic inflammatory pain was induced as time elapsed after the immunization of arthrogenic collagen and the maximum value was reached from third to fifth week. Chronic inflammatory pain induced by CIA was inhibited by bee venom acupuncture on the left ST36. The analgesic effect of bee venom acupuncture was inhibited by intraperitoneal injection of 5-HT1a antagonist spiroxatrine and 5-HT2a antagonist spiperone. Conclusions : Therefore, a conclusion. that the analgesic effect of bee venom acupuncture in the chronic inflammatory pain is partially mediated by 5-HT1a and 5-HT2a receptors can be made.

• The Korean Journal of Pain
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• v.22 no.1
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• pp.58-64
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• 2009

Background: Magnesium is a noncompetitive antagonist of the N-methyl-D aspartate (NMDA) receptor. Magnesium is thought to be involved in opioid tolerance by way of inhibiting calcium entry into cells. Methods: The patients were randomly assigned to three groups according to the anesthetic regimens: Group M received magnesium sulfate and Group C received saline intravenously under remifentanil-based anesthesia. Group S received saline intravenously under sevoflurane based anesthesia in place of remifentanil. The patients in the group M received 25% magnesium sulfate 50 mg/kg in 100 ml of saline, and those patients in groups C and S received an equal volume of saline before induction of anesthesia; this was followed by 10 mg/kg/h infusion of either magnesium sulfate (group M) or an equal volume of saline (groups C and S) until the end of surgery. Pain was assessed on a visual analog scale at 1, 6, 12, 24, and 36 hours after the operation. The time to the first postoperative analgesic requirement and the cumulative analgesic consumption were evaluated in the three groups. Results: The visual analog scales for pain and the cumulative analgesic consumption were significantly greater in group C than in other groups. The time to first postoperative analgesic requirement was significantly shorter in group C than that in the other groups. There were no differences between group M and S for side effects. Conclusions: A relatively high dose and continuous remifentanil infusion is associated with clinically relevant evidence of acute opioid tolerance. NMDA-receptor antagonist, magnesium sulfate as an adjuvant analgesic prevents opioid tolerance in patients who are undergoing major abdominal surgery under high dose and continuous remifentanil infusion-based anesthesia.

• The Korean Journal of Pharmacology
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• v.29 no.1
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• pp.9-22
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• 1993

To evaluate the protective effects of calcium antagonists, oxygen radical scavengers and excitatory amino acid (EAA) antagonist on the ischemic brain damage, we induced in vitro ischemic condition (namely, lack of oxygen and glucose) to rat hippocampal slices. And the degree of ischemic damage was determined by assaying changes in biochemical parameters such as ATP content and lactate ralease, MDA production in the presence or absence of the various drugs. During experimental ischemia for up to 60 min, ATP content was decreased and the amount of lactate release was markedly increased time-dependently. By changing the reaction medium which contained oxygen and glucose those biochemical parameters were recovered. But the recovery was not complete in this experimental condition. In the same ischemic conditions verapamil and vitamine E prevented the decrease of ATP content and the increase of lactate release from the slices. And verapamil and diltiazem decreased MDA release to the reaction medium. Superoxide dismutase (SOD) and MK-801 (as EAA receptor antagonist) protected the decrease of ATP content and reduced MDA release in 20 min ischemic condition, but glutathione affected ATP content and lactate release at the same condition. When oxygen and glucose were resupplied for 20 min after ischemic condition, verapamil showed the protective effect on the changes of ATP content and lactate release, and vitamine E decreased lactate release (at 20 min ischemia) and MDA release (at 60 min ischemia). These results showed that calcium antagonist and vitamine E protect the ischemic biochemical changes from rat hippocampal slices and calcium antagonist is more potent than vitamine E to protect the ischemical brain damege.

• The Korean Journal of Physiology and Pharmacology
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• v.1 no.5
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• pp.565-572
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• 1997

In the freshly isolated rat nephron, the effect of endothelin-1, -2 and -3 (ET-1, -2 and -3) on cytosolic free calcium concentration ($[Ca^{2+}]_i$) was determined using the fluorescent indicator Fura-2/AM. $[Ca^{2+}]_i$ increase was investigated in 9 parts of the single nephron including glomerulus (Glm), $S_1,\;S_2,\;S_3$, cortical and medullary thick ascending limb and cortical (CCT) and outer medullary collecting tubule (OMCT). Endothelins increased $[Ca^{2+}]_i$ in Glm (ET-1; $127{\pm}17%$, ET-2; $93{\pm}5%$, ET-3; $169{\pm}17%$), CCT (ET-1; $30{\pm}6%$, ET-2; $38{\pm}19%$, ET-3; $158{\pm}18%$) and OMCT (ET-1; $197{\pm}11%$, ET-2; $195{\pm}11%$, ET-3; $215{\pm}37%$) at 10-7 M. In OMCT, ET-1 and ET-2 increased $[Ca^{2+}]_i$ in a dose-dependent manner ($10^{-10}{\sim}10^{-6}$ M). To the contrary, ET-3-induced $[Ca^{2+}]_i$ rise was begun from $10^{-12}$ M. BQ-123Na, an antagonist of ETA receptor, at $10^{-4}$ M inhibited about 30% of $[Ca^{2+}]_i$ rise induced by ET-1 and -3. Binding experiments using $[^{125}I]ET-3$ showed the existence of $ET_B$ receptor in OMCT. This binding was replaced by ET-1, ET-2 or ET-3 by the almost same degree but not by angiotensin II or vasopressin.

• The Korean Journal of Physiology and Pharmacology
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• v.3 no.4
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• pp.383-391
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• 1999

This study was carried out to determine whether the effects of an ${\alpha}_2-adrenoceptor$ agonist, clonidine, on mean arterial pressure (MAP) and heart rate (HR) are influenced by mild hypothermia. Experiments were performed in respiration-controlled and spontaneously breathing pentobarbital-anesthetized rats. Rectal temperature was maintained at $37.5{\pm}0.3^{circ}C$ for normothermic groups or at $35.2{\pm}0.3^{circ}C$ for mild hypothermic groups. Intravenous injection of clonidine (1 and 2 ${\mu}g/kg)$ produced depressor and bradycardic responses in spontaneously breathing rats under both normothermic and mild hypothermic condition: a decrease in MAP was not altered but bradycardic response was significantly augmented in the mild hypothermic group as compared with the normothermic group. Under the respiration-controlled condition, the hypotensive effect of clonidine $(2\;{\mu}g/kg)$ was reduced, whereas the bradycardic effect was increased in mild hypothermic rats as compared with normothermic rats. Both hypotensive and bradycardic effects of clondine $(2\;{\mu}g/kg)$ were blocked by pretreatment with an ${\alpha}_2-adrenoceptor$ antagonist, yohimbine (0.5 mg/kg), in both thermal conditions. Yohimbine (0.5 mg/kg, i.v.) alone produced signifcantly an increase in heart rate in the mild hypothermic group than in the normothermic group. Pretreatment with a muscarinic receptor antagonist, atropine methylnitrate (1 mg/kg, i.v.), attenuated the bradycardic effect of clonidine in the mild hypothermic group but not in the normothermic group. These results suggest that clonidine- induced bradycardia is amplified by mild hypothermia probably through an increased parasympathetic activity.

• The Korean Journal of Physiology and Pharmacology
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• v.6 no.1
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• pp.27-31
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• 2002

${\gamma}-Aminobutyric$ Acid (GABA) is contained in pancreatic islet ${\beta}-cells$ although its physiological role in pancreatic exocrine function is completely unknown at the present time. Recently, we have reported that exogenous GABA enhances secretagogue-evoked exocrine secretion in the isolated, perfused rat pancreas. This study was aimed to investigate an effect of exogenous GABA on pancreatic exocrine secretion in vivo evoked by intestinal stimulation. Rats were anesthetized with urethane (1.4 g/kg) after 24-h fast with free access to water. GABA $(10,\;30\;and\;100\;{\mu}mol/kg/h),$ given intravenously, did not change spontaneous pancreatic amylase secretion but dose-dependently elevated the amylase secretion evoked by intraduodenal sodium oleate (0.05 mmol/h). GABA $(30\;{\mu}mol/kg/h)$ also further increased the amylase secretion stimulated by CCK (30 pmol/kg/h) plus secretin (20 pmol/kg/h) but failed to modify the amylase secretion induced by secretin alone. GABA $(10,\;30\;and\;100\;{\mu}mol/kg/h)$ also dose-dependently elevated pancreatic amylase secretion evoked by CCK alone. Bicuculline $(100\;{\mu}mol/kg/h),$ a $GABA_A-receptor$ antagonist, markedly reduced the GABA-enhanced pancreatic responses to sodium oleate, CCK plus secretin or CCK alone. The results indicate that GABA enhances the sodium oleate-evoked pancreatic amylase secretion via $GABA_A-receptor$ in anesthetized rats, which may account for elevating the action of CCK released by sodium oleate.