• Biomolecules & Therapeutics
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• 제11권4호
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• pp.214-223
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• 2003

Methamphetamine (METH) and 3,4-methylenedioxymethamphetamine (MDMA) have become popular recreational drugs of abuse in many countries. Although the neurotoxic damage caused by METH and MDMA is characterized by degeneration of the dopaminergic and serotonergic systems in brain, the molecular and cellular mechanisms remain to be clarified. Therefore, the purposes of this study were to confirm the capability of METH and MDMA to induce apoptosis and to clarify the action of its molecular mechanism by using serotonergic JAR cells and dopaminergic SK-N-SH cells. METH and MDMA were dose-dependently cytotoxic to human serotonergic JAR cells and dopaminergic SK-N-SH cells. The morphological change of apoptosis was found in Giemsa staining and TUNEL and further verified in DNA fragmentation analysis. Immunoblotting analysis revealed proteolytic cleavage of caspase-3 and -9 and change of bcl-2 and bax proteins. These results suggest that METH and MDMA may induce caspase-dependent apoptosis via the mitochondrial cell death pathway and METH and MDMA-induced neurotoxicity may happen to broadly and independently of both dopaminergic and serotonergic systems.

• Journal of Ginseng Research
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• 제19권3호
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• pp.202-205
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• 1995

We have previously reported that the antagonism of U-50,488H-induced antinociception in mice pretreated with ginseng total saponins (GTS) Ivas abolished by pretreatment with a serotonin precursor, 5-hydroxytryptophan (5-HTP), but not by a noradrenaline precursor, L-dihydroxyphenylalanine (L-DOPA) in the tail flick test. In the present experiments, the effect of the same GTS on the development of tolerance to U-50,488H-induced antinociception was determined. GTS inhibited the development of tolerance to U-50,488H-induced antinociception. The inhibitory effect of GTS on the development of tolerance to U-50,488H-induced antinociception was reversed by 5-HTP, but not by L-DOPA. These findings suggest that the inhibitory effect of GTS on the development of tolerance to U-50,488H-induced antinociception is dependent on serotonergic mechanisms. Key words Ginseng total saponin, U-50,488H, tolerance, serotonin.

• Journal of Ginseng Research
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• 제16권2호
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• pp.93-98
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• 1992

This study examined the Influence of ginseng total saponins (GTS) on the analgestic action and tolerance development of pentazocine in mice. Pentazocine prolonged the latency to response in the tail flick rather than in the tail pinch test. The analgesic effect of pentaEocine was antagonized by naloxone and completely eliminated by pretreatment u·ith f-chlorophenylalanine (PCPA). GTS provented the pentasocine-incuced analgesia ann inhibited the development of tolerance to pentazocine. The antagonistic effect of GTS on the pentazocine-induced analgesia was abolished by 5-HTP, but not by L-DOPA. These results suggest that GTS inhibits the analgesic action of pentazocine by the interaction with serotonergic neuron.

• The Korean Journal of Pain
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• 제24권4호
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• pp.179-184
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• 2011

Background: The analgesic mechanisms of cyclooxygenase (COX)-2 inhibitors have been explained mainly on the basis of the inhibition of prostaglandin biosynthesis. However, several lines of evidence suggest that their analgesic effects are mediated through serotonergic or adrenergic transmissions. We investigated the roles of these neurotransmitters in the antinociception of a selective COX-2 inhibitor at the spinal level. Methods: DUP-697, a selective COX-2 inhibitor, was delivered through an intrathecal catheter to male Sprague-Dawley rats to examine its effect on the flinching responses evoked by formalin injection into the hindpaw. Subsequently, the effects of intrathecal pretreatment with dihydroergocristine, prazosin, and yohimbine, which are serotonergic, ${\alpha}1$ adrenergic and ${\alpha}2$ adrenergic receptor antagonists, respectively, on the analgesia induced by DUP-697 were assessed. Results: Intrathecal DUP-697 reduced the flinching response evoked by formalin injection during phase 1 and 2. But, intrathecal dihydroergocristine, prazosin, and yohimbine had little effect on the antinociception of intrathecal DUP-697 during both phases of the formalin test. Conclusions: Intrathecal DUP-697, a selective COX-2 inhibitor, effectively relieved inflammatory pain in rats. Either the serotonergic or adrenergic transmissions might not be involved in the analgesic activity of COX-2 inhibitors at the spinal level.

• 한국자원식물학회지
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• 제23권6호
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• pp.513-518
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• 2010

In the present study, the antinociceptive profiles of Dianthus chinensis L extract were examined in ICR mice. Dianthus chinensis L extract administered orally (200 mg/kg) showed an antinociceptive effect as measured by the tail-flick and hot-plate tests. In addition, Dianthus chinensis L extract attenuated the writhing numbers in the acetic acid-induced writhing test. Furthermore, the cumulative nociceptive response time for intrathecal (i.t.) injection of substance P ($0.7\;{\mu}g$) was diminished by Dianthus chinensis L extract. Intraperitoneal (i.p.) pretreatment with yohimbine ($\alpha_2$-adrenergic receptor antagonist) attenuated antinociceptive effect induced by Dianthus chinensis L extract in the writhing test. However, naloxone (opioid receptor antagonist) or methysergide (5-HT serotonergic receptor antagonist) did not affect antinociception induced by Dianthus chinensis L extract in the writhing test. Our results suggest that Dianthus chinensis L extract shows an antinociceptive property in various pain models. Furthermore, this antinociceptive effect of Dianthus chinensis L extract may be mediated by $\alpha_2$-adrenergic receptor, but not opioidergic and serotonergic receptors.

• Biomolecules & Therapeutics
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• 제20권6호
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• pp.506-512
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• 2012

Although pruritus is the critical symptom of atopic dermatitis that profoundly affect the patients' quality of life, controlling and management of prurirtus still remains as unmet needs mainly due to the distinctive multifactorial pathogenesis of pruritus in atopic dermatitis. Based on the distinct feature of atopic dermatitis that psychological state of patients substantially influence on the intensity of pruritus, various psychotropic drugs have been used in clinic to relieve pruritus of atopic dermatitis patients. Only several psychotropic drugs were reported to show real antipruritic effects in atopic dermatitis patients including naltrexone, doxepin, trimipramine, bupropion, tandospirone, paroxetine and fluvoxamine. However, the precise mechanisms of antipruritic effect of these psychotropic drugs are still unclear. In human skin, serotonin receptors and serotonin transporter protein are expressed on skin cells such as keratinocytes, melanocytes, dermal fibroblasts, mast cells, T cells, natural killer cells, langerhans cells, and sensory nerve endings. It is noteworthy that serotonergic drugs, as well as serotonin itself, showed immune-modulating effect. Fenfluramine, fluoxetine and 2, 5-dimethoxy-4-iodoamphetamine significantly decreased lymphocyte proliferation. It is still questionable whether these serotonergic drugs exert the immunosuppressive effects via serotonin receptor or serotonin transporter. All these clinical and experimental reports suggest the possibility that antipruritic effects of selective serotonin reuptake inhibitors in atopic dermatitis patients might be at least partly due to their suppressive effect on T cells. Further studies should be conducted to elucidate the precise mechanism of neuroimmunological interaction in pruritus of atopic dermatitis.

• Archives of Pharmacal Research
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• 제16권3호
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• pp.237-243
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• 1993

These studies were performed to investigate the acting sites of ginseng total saponins (GTS) on the U-50, 488H-induced antinociception and the inhibitory effect of the development of tolerance to U-50, 488H-induced antinociception by GTS were studied. The U-50, 488H-induced antinociception was ntagonized in mice pretreated with GTS intraperitoneally, intracerebrally. These antagonisms were reversed by the pretratment iwth a serotonin precursor, 5-hydroxytrypophan (5-HTP), but not with a noradrenaline precursor, L-dihydroxyphenylalanine (L-DOPA). However, the intraplantar sites. On the other hand, GTS inhibited the development of tolerance to U-50, 488H-induced antinociception was reversed by pretreatment with 5-HTP, but not with L-DOPA. Therefore, the antagonism of U-50, 488H-induced antinociception and the inhibition of the development of tolerance to U-50, 488H-induced antinociception and the inhibition of the development of tolerance to U-50, 488H-induced antinociception by GTS are dependent on serotonegic mechanisms.

• 한국약용작물학회지
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• 제18권4호
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• pp.238-243
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• 2010

In the present study, the antinociceptive profiles of Viola tricolor L. (V. tricolor L.) extract were examined in ICR mice. V. tricolor L. extract administered orally (200mg/kg) showed an antinociceptive effect as measured by the tail-flick and hot-plate tests. In addition, V. tricolor L. extract attenuated the writhing numbers in the acetic acid-induced writhing test. Furthermore, the cumulative nociceptive response time for intrathecal (i.t.) injection of substance P (0.7 ${\mu}g$) was diminished by V. tricolor L. extract. Intraperitoneal (i.p.) pretreatment with yohimbine (${\alpha}_2$-adrenergic receptor antagonist) attenuated antinociceptive effect induced by V. tricolor L. extract in the writhing test. However, naloxone (opioid receptor antagonist) or methysergide (5-HT serotonergic receptor antagonist) did not affect antinociception induced by V. tricolor L. extract in the writhing test. Our results suggest that V. tricolor L. extract shows an antinociceptive property in various pain models. Furthermore, this antinociceptive effect of V. tricolor L. extract may be mediated by ${\alpha}_2$-adrenergic receptor, but not opioidergic and serotonergic receptors.

• The Korean Journal of Physiology and Pharmacology
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• 제16권2호
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• pp.119-123
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• 2012

In the present study, the antinociceptive profiles of $Agrimonia$ $pilosa$ $Ledeb$ extract were examined in ICR mice. $Agrimonia$ $pilosa$ $Ledeb$ extract administered orally (200 mg/kg) showed an antinociceptive effect as measured by the tail-flick and hot-plate tests. In addition, $Agrimonia$ $pilosa$ $Ledeb$ extract attenuated the writhing numbers in the acetic acid-induced writhing test. Furthermore, the cumulative nociceptive response time for intrathecal (i.t.) injection of substance P (0.7 ${\mu}g$) was diminished by $Agrimonia$ $pilosa$ $Ledeb$ extract. Intraperitoneal (i.p.) pretreatment with yohimbine (${\alpha}_2$-adrenergic receptor antagonist) attenuated antinociceptive effect induced by $Agrimonia$ $pilosa$ $Ledeb$ extract in the writhing test. However, naloxone (opioid receptor antagonist) or methysergide (5-HT serotonergic receptor antagonist) did not affect antinociception induced by $Agrimonia$ $pilosa$ $Ledeb$ extract in the writhing test. Our results suggest that $Agrimonia$ $pilosa$ $Ledeb$ extract shows an antinociceptive property in various pain models. Furthermore, this antinociceptive effect of $Agrimonia$ $pilosa$ $Ledeb$ extract may be mediated by ${\alpha}_2$-adrenergic receptor, but not opioidergic and serotonergic receptors.

• The Korean Journal of Physiology and Pharmacology
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• 제14권5호
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• pp.285-289
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• 2010

In the present study, the antinociceptive profiles of $Campanula$ $punctata$ extract were examined in ICR mice. The $Campanula$ $punctata$ contain a large dose of saponin. $Campanula$ $punctata$ extract administered orally (200 mg/kg) showed an antinociceptive effect as measured by the tail-flick and hot-plate tests. In addition, $Campanula$ $punctata$ extract attenuated the writhing numbers in the acetic acid-induced writhing test. Furthermore, the cumulative nociceptive response time for intrathecal (i.t.) injection of substance P ($0.7{\mu}g$) was diminished by $Campanula$ $punctata$ extract. Intraperitoneal (i.p.) pretreatment with yohimbine (${\alpha}_2$-adrenergic receptor antagonist) attenuated antinociceptive effect induced by $Campanula$ $punctata$ extract in the writhing test. However, naloxone (opioid receptor antagonist) or methysergide (5-HT serotonergic receptor antagonist) did not affect antinociception induced by $Campanula$ $punctata$ extract in the writhing test. Our results suggest that $Campanula$ $punctata$ extract shows an antinociceptive property in various pain models. Furthermore, this antinociceptive effect of $Campanula$ $punctata$ extract may be mediated by ${\alpha}_2$-adrenergic receptor, but not opioidergic and serotonergic receptors.