• Bulletin of the Korean Chemical Society
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• 제30권5호
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• pp.1107-1112
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• 2009

The aim of this study is to develop and synthesize $5-HT_{1A}$ receptor imaging agents with WAY-100635 moiety and $^{99m}Tc(CO)_3$ core. WAY-100635 is commonly known as $5-HT_{1A}$ antagonist and its labeled compound ([$^{11}C$] WAY-100635) has been used as effective radioligand for imaging brain $5-HT_{1A}$ receptors with PET(Positron Emission Tomography). However, there are several restrictions in using a radioisotope of C-11 and requires for more effective radioisotopes and ligands. In order to produce a structure most similar to WAY-100635, WAY-100635 derivatives containing a cysteine chelator were designed and confirmed by using in silico (Hyperchem). The novel compounds (7a, 7b, 7c) were prepared in five or 7 steps with yields of 16%, 36% and 42%, respectively and radiolabeled with $[^{99m}Tc(CO)_3(H_2O)_3]^{+}$. The labeling yield was 99% for all the newly synthesized compounds. [$^{99m}Tc(CO)_3$]- WAY-100635 derivatives show a neutral charge which were confirmed by paper electrophoresis.

• Advances in Traditional Medicine
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• 제9권2호
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• pp.135-141
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• 2009

The purpose of this study was to characterize the putative anxiolytic-like effects of the 70% ethanol extract of Portulaca oleracea (EPO) using an elevated plus maze (EPM) in mice. The EPO was orally administered at 50, 100, 200 or 400 mg/kg to ICR mice, 1 h before the behavioral evaluation in the EPM, respectively. Control mice were treated with an equal volume of 10% tween 80, and positive control mice with diazepam (1 mg/kg). Single treatments of the EPO significantly increased the percentage of time spent and arm entries into the open arms of the EPM versus controls (P < 0.05). Moreover, there were no changes in the locomotor activity and myorelaxant effects in any group compared with the saline controls. In addition, the anxiolytic-like effects of the EPO were blocked by flumazenil (10 mg/kg, i.p), a $GABA_A$ antagonist not by WAY 100635 (0.3 mg/kg, i.p), a 5-$HT_{1A}$ receptor antagonist. These results indicate that P. oleracea is an effective anxiolytic agent, and suggest that the anxiolytic-like effects of P. oleracea is mediated via the GABAergic nervous system.

• Biomolecules & Therapeutics
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• 제13권2호
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• pp.84-89
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• 2005

The purpose of this study was to characterize the putative anxiolytic-like effects of the aqueous extract of the root of Polygala tenuifolia ( AEPT) using an elevated plus maze (EPM) and hole-board apparatus in mice. The AFPT was orally administered at 50, 100, 200 or 400 mg/kg to ICR mice, 1 h before the behavioral evaluation in the EPM respectively. Control mice were treated with an equal volume of saline, and positive control mice with buspirone (2 mg/kg). Single treatments of the AEPT significantly increased the percentage of time spent and arm entries into the open arms of the EPM vedrsus saline controls (P<0.05). Moreover, there were no changes in the locomotor activity and myorelaxant effects in any group compared with the saline controls. In the hole-board test,single treatments of the AEPT (200 and 400 mg/kg) significantly increased the number of headdips versus saline controls (P<0.05). In addition, the anxiolytic-like effects of the AEPT were blocked by WAY 100635(0.3mg/kg, I.p), a5-$HT_{1A}$ receptor antagonist not by flumazenil, a $GABA_{A}$ antagonist. These results indicate that P. tenuifolia is an effective anxiolytic agent, andsuggest that the anxiolytic-like effects of P. tenuifolia is mediated via the serotonergic nervous system.

• 동의생리병리학회지
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• 제24권3호
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• pp.476-483
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• 2010

The present study was performed to investigate the putative anxiolytic-like effects of the aqueous extract of the roots of Scrophularia buergeriana (SB-W) using elevated plus-maze (EPM) and hole-board apparatus in mice. SB-W was orally administered at doses of 50, 100, 200 or 400 mg/kg to ICR mice, 1 h before the behavioral evaluation. Control group were administered with an equal volume of saline, and positive control group with buspirone (2 mg/kg, i.p.). The administration of SB-W significantly increased the percentage of time spent in open arms and entries into the open arms of the EPM compared with saline-treated control group (P < 0.05). Futhermore, those anxiolytic-like activities of SB-W were antagonized by flumazenil (a $GABA_A$ antagonist, 10 mg/kg), but not by WAY-100635 (a 5-$HT_{1A}$ antagonist, 0.3 mg/kg). Moreover, there were no changes in the locomotor activity and myorelaxant effects in any group compared with saline-treated control group. In the hole-board test, the administration of SB-W (200 and 400 mg/kg) significantly increased the number of head-dipping compared with saline-treated control group (P < 0.05). Therefore, these findings suggest that Scrophularia buergeriana promotes the anxiolytic-like activity mediated by GABAergic nervous system in mice.

• Bulletin of the Korean Chemical Society
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• 제31권8호
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• pp.2371-2374
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• 2010

• 한국콘텐츠학회논문지
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• 제9권11호
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• pp.262-270
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• 2009

세로토닌 수용체 5-$HT_{1A}$에 대한 방사성추적자로 알려진 $^{18}F$-mefway를 개선된 방법으로 합성하고, 소 동물 뇌 microPET 연구를 통해서 이 수용체에 선택적으로 결합하는 지를 확인하려고 한다. 기존 합성 방법을 수정하여 전구체를 합성하고, $[^{18}F]^-$과 $130^{\circ}C$에서 30분간 교반하여 $^{18}F$-mefway를 합성하여, Solid phase extraction(SPE)과 HPLC를 이용해 정제한 다음, 소동물 뇌의 microPET 다이나믹 영상을 얻었다. Oxalyl chloride와 LAH/diethyl ether을 사용해서 기존 합성수율 9%에서 34%로 $^{18}F$-mefway 전구체를 향상된 수율로 합성할 수 있는 개선된 방법을 확립하였다. 이렇게 합성된 $^{18}F$-mefway는 세로토닌 5-$HT_{1A}$수용체 영상용 방사성 의약품으로서 신경정신질환 연구에 이용될 수 있을 것으로 사료된다.

• 한국식품저장유통학회지
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• 제19권5호
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• pp.767-773
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• 2012

괴각 추출물의 항불안 효능을 탐색하기 위하여 elevated plus-maze, horizontal wire test 및 open field test와 같은 동물행동실험을 통하여 비교한 결과 다음과 같은 결론을 얻었다. Elevated plus-maze를 이용한 본 연구에서 괴각 추출물의 100 mg/kg, 200 mg/kg 및 400 mg/kg 투여군에서 대조군에 비하여 open arm에서 머무른 시간의 백분율이 증가하였고, open arm으로의 출입 백분율 또한 증가하였다. Elevated plus-maze를 이용한 길항실험에서는 benzodiazepine 수용체의 antagonist인 flumazenil에 의해 괴각 추출물 400 mg/kg의 항불안 효능이 차단되는 것이 관찰되었다. Locomotor activity 측정에서도 괴각 추출물의 모든 용량에서 총 이동거리의 변화가 없었으며, 또한 horizontal wire test에서도 대조군과 괴각 추출물 투여군 사이에 차이를 나타내지 않았다. 결론적으로, 본 연구의 결과에서 괴각의 메탄올 추출물이 elevated plus-maze test, horizontal wire test 및 open field test를 통하여 locomotor activity 및 근육이완이나 진정 등의 부작용이 없으면서 우수한 항불안 작용을 가지는 천연물이라고 생각되어지며 이러한 작용이 특히 GABA 신경계와 관련이 있음을 시사하고 있다. 향후 괴각의 항불안 작용의 평가를 위하여 다양한 실험모델의 개발이 필요할 것으로 생각되며 또한 이러한 작용에 대한 기전 연구가 포괄적이고 다각적으로 진행되어져야 할 필요성이 있다고 사료된다.

• 생명과학회지
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• 제24권3호
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• pp.290-296
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• 2014

이 연구의 목적은 mice를 이용하여 elevated plus-maze (EPM) test와 hole-board test를 통해 quercetin의 잠재적인 항불안 작용을 확인하고자 함이다. Quercetin을 1.25, 2.5, 5나 10 mg/kg의 용량으로 각각 행동시험을 측정하기 1 시간 전에 ICR mice에 경구투여하였다. 대조군은 동일한 양의 10% Tween 80을 투여하였고 양성대조군으로 buspirone 2 mg/kg을 투여하였다. Quercetin을 단회 투여하여 EPM test를 실시한 결과, 5 mg/kg 용량에서 open arm에 머문 시간 및 진입한 횟수의 백분율이 control group과 비교하여 통계적으로 유의성 있게 증가하였다(p<0.05). 또한 quercetin을 투여하여 hole-board test를 실시한 결과, 5 mg/kg 용량에서 구멍에 머리를 넣은 횟수가 control group과 비교하여 통계적으로 유의성 있게 증가하였다(p<0.05). 또한 quercetin와 flumazenil ($GABA_A$ antagonist), WAY-100635 ($GABA_{A-{\rho}}$ antagonist) 또는 trans-4-aminocrotonic acid ($GABA_{A-{\rho}}$ agonist)를 병용투여하여 elevated plus-maze를 실험을 하여 신경계와의 관계를 확인한 결과, trans-4-aminocrotonic acid에서만 quercetin의 항불안 작용이 차단되었음을 확인 할 수 있었다. 결론적으로, 본 연구의 결과에서 quercetin이 elevated plus-maze 및 hole-board test, horizontal wire test, open field test를 통하여 locomotor activity 및 근육이완이나 진정 등의 부작용이 없으면서 우수한 항불안 작용을 가지는 소재라고 생각되며 이러한 작용이 특히 GABA 신경계와 관련이 있음을 시사하고 있다.

• The Korean Journal of Physiology and Pharmacology
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• 제11권5호
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• pp.221-226
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• 2007

Melittin-induced tonic pain model is characterized by local inflammation, edema, spontaneous flinchings, and sustained mechanical hypersensitivity. These nociceptive responses are mediated through selective activation of capsaicin-sensitive primary afferent fibers by melittin. The present study was undertaken to elucidate the role of peripheral 5-hydroxytryptamine(5-HT) receptors in the melittin-induced nociceptive responses. Changes in mechanical threshold, flinching behaviors and paw thickness were measured in rat intraplantarly injected with melittin($40{\mu}g/paw$) alone or treated together with melittin and 5-HT receptor antagonists. WAY-100635($100{\mu}g\;&\;200{\mu}g/paw$), isamoltane hemifumarate($100{\mu}g\;&\;200{\mu}g/paw$), methysergide maleate($60{\mu}g,\;120{\mu}g\;&\;200{\mu}g/paw$) and ICS-205,930($100{\mu}g\;&\;200{\mu}g/paw$) were intraplantarly injected 20 min before melittin injection. All 5-HT receptor antagonists tested in this experiment significantly attenuated the ability of melittin to reduce mechanical threshold and to induce flinching behaviors. 5-HT receptor antagonists, except ICS-205,930, had mild inhibitory effect on melittin-induced edema. These experimental findings suggest that multiple peripheral 5-HT receptors are involved in the melittin-induced nociceptive responses.

• The Korean Journal of Physiology and Pharmacology
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• 제25권5호
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• pp.489-494
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• 2021

Oxaliplatin, a third-generation platinum derivative, is the mainstay of current antineoplastic medications for advanced colorectal cancer therapy. However, peripheral neuropathic complications, especially cold allodynia, undermine the life-prolonging outcome of this anti-cancer agent. Rosavin, a phenylpropanoid derived originally from Rhodiola rosea, exhibits a wide range of therapeutic properties. The present study explored whether and how rosavin alleviates oxaliplatin-induced cold hypersensitivity in mice. In the acetone drop test, cold allodynia behavior was observed from days 3 to 5 after a single injection of oxaliplatin (6 mg/kg, i.p.). Cold allodynia was significantly attenuated following rosavin treatment (10 mg/kg, i.p.). Specific endogenous 5-HT depletion by three consecutive pretreatments with parachlorophenylalanine (150 mg/kg/day, i.p.) abolished the analgesic action of rosavin; this effect was not observed following pretreatment with naloxone (opioid receptor antagonist, 10 mg/kg, i.p.). Furthermore, 5-HT_1A receptor antagonist WAY-100635 (0.16 mg/kg, i.p.), but not 5-HT₃ receptor antagonist MDL-72222 (1 mg/kg, i.p.), blocked rosavin-induced analgesia. These results suggest that rosavin may provide a novel approach to alleviate oxaliplatin-induced cold allodynia by recruiting the activity of 5-HT_1A receptors.