• Sleep Medicine and Psychophysiology
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• v.7 no.1
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• pp.10-17
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• 2000

To investigate the neurobiological bases of learning and memory is one of the ambitious goals of modern neuroscience. The progress in this field of recent years has not only brought us closer to understanding the molecular mechanism underlying long-lasting changes in synaptic strength, but it has also provided further evidence that these mechanisms are required for memory formation. Since twenty years ago, several studies for the tests of the hypothesis that NMDA-dependent hippocampal long-term potentiation(LTP) underlies learning have been reported. Also, in the recent year, data from mutant mice showed that a potential role for NMDA-dependent LTP in hippocampal CA1 and spatial learning. Although the current evidence for the role of NMDA receptor in learning and memory is not still obvious, NMDA receptor seems to act as a critical switch for activation of a cascade of events that underlie synaptic plasticity.

• The Korean Journal of Pharmacology
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• v.10 no.1 s.15
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• pp.61-65
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• 1974

Berberis koreana Palibin belonging to Berberidaceae family, a common herb in Korea, has been contained some quantity of Berberine analogue and other ingredients. Authors therefore paid attention to its pharmacological actions and examined the effects on sleep duration and rectal temperature in mouse with crystal (A) from Berberis koreana Palibin in Korean native plans. The experiment searching for the effect on sleep duration was performed with pretreatment of Berberis Koreana Palibin crystal (A) 30 min before the administration of 25 % ethanol, and its crystal were also administered intraperitoneally with the intention to examine the effect on rectal temperature in mouse. The results of the experiment were as follows; 1. Crystal (A) from Berberis koreana Palibin was made by extraction with ethanol and HCI. 2. Crystal (A) enhanced the hypnotic activity of alcohol in concentratins of 0.1 mg/10g or 0.15 mg/10g. 3. Rectal temperatures in mice were significantly reduced with administration of crystal (A) in concentrations of 0.1 mg/10g or 0.15 mg/10g. 4. The maximal reduction of rectal temperature and potentiation of the hypnotic activity were observed at 30 min after its administration. From the above results, it is clear that crystal (A) from Berberis koreana Palibin exerts the potentiation of hypnotic action of alcohol and reduction of rectal temperature in normal mouse. Its pharmacological effects are probably derived from the action upon the central nervous system.

• Sleep Medicine and Psychophysiology
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• v.3 no.1
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• pp.15-24
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• 1996

After rapid eye movement(REM) sleep was idenified in 1953, a lively interest developed concerning a possible role of this kind of sleep in memory processes. The author reviewed studies relating REM to memory/learning. Many studies in animals and humans gave substantial evidence for relating REM sleep to memory function. The evidence supporting the position taken in this paper comes from experiments showing that : (1) learning session is followed by the significant augmentation of REM sleep : (2) REM sleep deprivation, prior to learning or immediately thereafter, impairs the formation of a permanent memory/learning : (3) there is a vulnerable period of time(eg, REM sleep "window") following succussful learning, during which REM sleep deprivation results in memory impairment : (4) theta rhythm which develops during REM sleep induces long-term potentiation in hippocampus : (5) there are some evidences providing the relationship of neurotransmitter systems to the maintenance of REM sleep and memory storage processes.

• Sleep Medicine and Psychophysiology
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• v.6 no.1
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• pp.19-25
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• 1999

Sleep alters both breathing pattern and the ventilatory responses to external stimuli. These changes during sleep permit the development or aggravation of sleep-related hypoxemia in patients with respiratory disease and contribute to the pathogenesis of apneas in patients with the sleep apnea syndrome. Fundamental effects of sleep on the ventilatory control system are 1) removal of wakefulness input to the upper airway leading to the increase in upper airway resistance, 2) loss of wakefulness drive to the respiratory pump, 3) compromise of protective respiratory reflexes, and 4) additional sleep-induced compromise of ventilatory control initiated by reduced functional residual capacity on supine position assumed in sleep, decreased $CO_2$ production during sleep, and increased cerebral blood flow in especially rapid eye movement(REM) sleep. These effects resulted in periodic breathing during unsteady non-rapid eye movement(NREM) sleep even in normal subjects, regular but low ventilation during steady NREM sleep, and irregular breathing during REM sleep. Sleep-induced breathing instabilities are divided due primarily to transient increase in upper airway resistance and those that involve overshoots and undershoots in neural feedback mechanisms regulating the timing and/or amplitude of respiratory output. Following ventilatory overshoots, breathing stability will be maintained if excitatory short-term potentiation is the prevailing influence. On the other hand, apnea and hypopnea will occur if inhibitory mechanisms dominate following the ventilatory overshoot. These inhibitory mechanisms include 1) hypocapnia, 2) inhibitory effect from lung stretch, 3) baroreceptor stimulation, 4) upper airway mechanoreceptor reflexes, 5) central depression by hypoxia, and 6) central system inertia. While the respiratory control system functions well during wakefulness, the control of breathing is commonly disrupted during sleep. These changes in respiratory control resulting in breathing instability during sleep are related with the pathophysiologic mechanisms of obstructive and/or central apnea, and have the therapeutic implications for nocturnal hypoventilation in patients with chronic obstructive pulmonary disease or alveolar hypoventilation syndrome.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.1
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• pp.27-36
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• 2017

Angelicae Gigantis Radix (AGR, Angelica gigas) has been used for a long time as a traditional folk medicine in Korea and oriental countries. Decursinol angelate (DCA) is structurally isomeric decursin, one of the major components of AGR. This study was performed to confirm whether DCA augments pentobarbital-induced sleeping behaviors via the activation of $GABA_A$-ergic systems in animals. Oral administration of DCA (10, 25 and 50 mg/kg) markedly suppressed spontaneous locomotor activity. DCA also prolonged sleeping time, and decreased the sleep latency by pentobarbital (42 mg/kg), in a dose-dependent manner, similar to muscimol, both at the hypnotic (42 mg/kg) and sub-hypnotic (28 mg/kg) dosages. Especially, DCA increased the number of sleeping animals in the sub-hypnotic dosage. DCA (50 mg/kg, p.o.) itself modulated sleep architectures; DCA reduced the counts of sleep/wake cycles. At the same time, DCA increased total sleep time, but not non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. In the molecular experiments. DCA (0.001, 0.01 and $0.1{\mu}g/ml$) increased intracellular Cl- influx level in hypothalamic primary cultured neuronal cells of rats. In addition, DCA increased the protein expression of glutamic acid decarboxylase ($GAD_{65/67}$) and $GABA_A$ receptors subtypes. Taken together, these results suggest that DCA potentiates pentobarbital-induced sleeping behaviors through the activation of $GABA_A$-ergic systems, and can be useful in the treatment of insomnia.

• Archives of Pharmacal Research
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• v.27 no.12
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• pp.1194-1201
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• 2004

Michael addition of certain nucleophiles on ${\alpha}$ , ${\beta}$-unsaturated ketones 1 led to the formation of adducts 2-7 as well as the reaction of arylidene derivatives with secondary amines afforded the amino compounds 9 and 11. Also, dialkylmalonates were treated with ${\alpha}$-cyano cinnamide to afford 13. On the other hand, double Michael cycloaddition of ethylcyanoacetate or tetrachlorophthalic anhydride to the suitable divinylketone were synthesized to produce 15-17. Selected compounds (13 and 6) were screened for muscle relaxant, anticonvulsant, and sedative activities using established pharmacological models. Their activities were compared with that of phenobarbital sodium taken as standard. Compound 6 was the most potent muscle relaxant while compounds 13a and 13c offered the highest anticonvulsant activity. Meanwhile compound 13c showed the highest potentiation of phenobarbital induced sleep in mice.

• Korean Journal of Pharmacognosy
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• v.24 no.3
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• pp.231-234
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• 1993

Neuropharmacological profile of Humulus lupulus (hop) extract was studied in mice. At doses above 100 mg/kg(i.p.), it decreased spontaneous locomotor activity and raised the nociceptive threshold in the hot-plate test. At doses above 250 mg/kg (i.p.), it increased pentobarbital-induced sleeping time and produced muscle relaxant effect. At the dose of 500 mg/kg, anticonvulsive effect against pentylenetetrazole-induced convulsion and hypothermic effect was observed.

• Journal of Oriental Neuropsychiatry
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• v.13 no.2
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• pp.195-211
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• 2002

Gagamguibitang, a composite Korean medicinal drug prescribed by us, was evaluated for its sedative effects by measurements of potentiation on pentobarbital-induced sleeping time, anticonvulsive activities in animal model, inhibitory effect on GABA transaminase activity, and antioxidative activities in vitro- and/or in vivo assay. The results were summerized as follows : 1. Gagamguibitang showed about 2-fold prolongation of pentobarbital-induced sleeping time compared to the control group after administration(p.o) with 2.0g/kg of mice body weight. 2. Gagamguibitang strongly lengthened onset time of pentylenetetrazole-induced convulsion, shortened the duration of convulsion and diminished the lethality after treatment(p.o) with 1.0g/kg of mice body weight. 3. Gagamguibitang inhibited dose-dependently the brain GABA transaminase activity in vitro compared to the control group and in vivo compared to the pentylenetetrazole-treated group. 4. Gagamguibitang inhibited effectively brain lipid peroxidation by 45.8% at a dose of l0mg/ml in vitro and by 47.5% after oral treatment with 0.5g/kg of mice body weight in vivo assay. 5. Gagamguibitang exhibited a potent scavenging activity on DPPH radical in a dose-dependent manner with ca. 92% activity at l0mg/ml. As a result, Gagamguibitang can be useful for the effective sedative drug in clinical application.