• Bulletin of the Korean Chemical Society
• /
• v.30 no.5
• /
• pp.1107-1112
• /
• 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
• /
• v.9 no.2
• /
• pp.135-141
• /
• 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
• /
• v.13 no.2
• /
• pp.84-89
• /
• 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.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.24 no.3
• /
• pp.476-483
• /
• 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
• /
• v.31 no.8
• /
• pp.2371-2374
• /
• 2010

• The Journal of the Korea Contents Association
• /
• v.9 no.11
• /
• pp.262-270
• /
• 2009

$^{18}F$-mefway has been developed as radioligand for serotonin receptor 5-$HT_{1A}$. The object of this study was to obtain the mefway precursor with the higher yield than previous method and to identify whether $^{18}F$-mefway can bind to 5-$HT_{1A}$ or not. from microPET imaging of small animal brain. Precursor was prepared by a modification of the reported procedure then [$^{18}F$] labeling was performed by adding $^{18}F$ ion at $130^{\circ}C$ in the hot cell for 30min. After purification of reaction mixture using alumina Sep-pak and HPLC, microPET images of small animal brain were determined. The chemical yield of precursor was increased from 9% to 34% using oxalyl chloride and LAH/diethylether. We synthesized a precursor which was successfully labeled with no-carrier-added $^{18}F$-by new synthetic route. This research suggest that $^{18}F$-mefway will be used a radiopharmaceutical for evaluation of central nerve system disorder as imaging a gent for 5-$HT_{1A}$ receptor.

• Food Science and Preservation
• /
• v.19 no.5
• /
• pp.767-773
• /
• 2012

The purpose of this study was to investigate the anxiolytic-like effect of the methanol extract of Sophorae fructus (MESF) using elevated plus-maze (EPM), open field test, and horizontal wire test in mice. MESF was orally administered at doses of 50, 100, 200, or 400 mg/kg to ICR mice 1 h before behavioral evaluation. The control group was given an equal volume of 10% Tween 80, and the positive control group was given diazepam (1 mg/kg, i.p.). The administration of MESF significantly increased the percentage of time spent in open arms and the entries into the open arms of the EPM compared with the 10% Tween 80-treated control group (p < 0.05). In addition, the anxiolytic-like activities of MESF were antagonized by flumazenil (a GABAA antagonist, 10 mg/kg) but not by WAY-100635 (a 5-HT1A antagonist, 0.3 mg/kg). Futhermore, there were no changes in the locomotor activity and myorelaxant effects of the experimental group, as opposed to the 10% Tween 80-treated control group. Therefore, these findings suggest that MESF promotes the anxiolytic-like activity mediated by the GABAergic nervous system in mice.

• Journal of Life Science
• /
• v.24 no.3
• /
• pp.290-296
• /
• 2014

The present experiment investigated putative anxiolytic-like effects of quercetin using an elevated plus-maze (EPM) and hole-board apparatus test in mice. Quercetin is a flavonoid widely distributed in nature. Quercetin (1.25, 2.5, 5, or 10 mg/kg) was orally administered to ICR mice 1 h before a behavioral evaluation in the EPM. Control mice were treated with an equal volume of vehicle, and positive control mice were treated with buspirone (2 mg/kg, i.p.). The mice administered quercetin (5 mg/kg) spent a significantly longer percentage of time in the open arms of the EPM and their percentage of entries into the open arms was significantly increased compared to the vehicle-treated controls (p<0.05). The anxiolytic-like activities of quercetin were antagonized by trans-4-aminocrotonic acid (a $GABA_{A-{\rho}}$ agonist, 20 mg/kg) but not by flumazenil (a $GABA_A$ antagonist, 10 mg/kg) or WAY-100635 (a $5-HT_{1A}$ antagonist, 0.3 mg/kg). Moreover, there were no changes in the locomotor activity or myorelaxant effects in any group compared with the vehicle-treated controls. In the hole-board apparatus test, the number of head-dips increased significantly in the single treatment with quercetin (5 mg/kg) group compared to the vehicle-treated controls (p<0.05). These findings suggest that quercetin can promote anxiolytic-like activity, mediated by the GABAergic nervous system, in mice.

• The Korean Journal of Physiology and Pharmacology
• /
• v.11 no.5
• /
• pp.221-226
• /
• 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
• /
• v.25 no.5
• /
• pp.489-494
• /
• 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.