Scientific Reports
·
2016
·Vol. 6
·期 1
·1-10
·
IF 5.228
Zhu Qing,Mao Li-Na,Liu Cheng-Peng,Sun Yue-Hua,Jiang Bo,Zhang Wei,Li Jun-Xu
Vitexin, a C-glycosylated flavone present in several medicinal herbs, has showed various pharmacological activities including antinociception. The present study investigated the antinociceptive effects of vitexin in a mouse model of postoperative pain. This model was prepared by making a surgical incision on the right hindpaw and von Frey filament test was used to assess mechanical hyperalgesia. Isobolographical analysis method was used to examine the interaction between vitexin and acetaminophen. A reliable mechanical hyperalgesia was observed at 2 h post-surgery and lasted for 4 days. Acute vitexin administration (3–10 mg/kg, i.p.) dose-dependently relieved this hyperalgesia, which was also observed from 1 to 3 days post-surgery during repeated daily treatment. However, repeated vitexin administration prior to surgery had no preventive value. The 10 mg/kg vitexin-induced antinociception was blocked by the opioid receptor antagonist naltrexone or the GABA A receptor antagonist bicuculline. The doses of vitexin used did not significantly suppress the locomotor activity. In addition, the combination of vitexin and acetaminophen produced an infra-additive effect in postoperative pain. Together, though vitexin-acetaminophen combination may not be useful for treating postoperative pain, vitexin exerts behaviorally-specific antinociception against postoperative pain mediated through opioid receptors and GABA A receptors, suggesting that vitexin may be useful for the control of postoperative pain.
研究领域:
药理学
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疼痛研究
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神经科学
✓ 已验证
DOI
高影响因子
EPILEPSIA
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2021
·Vol. 62
·期 1
·238-249
·
IF 5.866
Yi Zhao,Long An,Shupan Guo,Xiaoxing Huang,Huajie Tian,Li Liu,Tao Chen,Xun Sun,Qibing Mei,Rutao Wang
Objective LMR-101 is a bisphenol derivative of propofol, a short-acting general anesthetic, which is also used to manage status epilepticus (SE). We evaluated the sedative and anticonvulsant effects of LMR-101 to discover its potential to manage epilepsy and SE in the clinic. Methods Comparative studies between LMR-101 and propofol were performed in mice to elucidate an appropriate dose range for LMR-101 that produced anticonvulsant effects without significant sedation. Then, the anticonvulsive efficacy for LMR-101 was evaluated using seizure models induced by pentylenetetrazol and (+)-bicuculline. The ability of LMR-101 to inhibit SE was assessed using a rat model of SE induced by pilocarpine. Radioligand binding assay profiles for LMR-101 were performed to evaluate the potential mechanisms of action underlying its anticonvulsant properties. Results In the mouse study, LMR-101 exhibited greater anticonvulsant and lesser sedative effect compared with propofol. LMR-101 completely inhibited pentylenetetrazol-induced seizures at a dose of 50 mg/kg and exhibited heavy sedation at 300 mg/kg. Propofol anesthetized all mice and only decreased the seizure rate at 25 mg/kg. LMR-101 also suppressed seizure behaviors evoked by (+)-bicuculline in mice in a dose-dependent manner. In the pilocarpine-induced SE model, LMR-101 significantly decreased the maximum seizure score and seizure duration in a dose-dependent manner. The median effective dose for LMR-101 was 14.30 mg/kg and 121.87 mg/kg to prevent and inhibit sustained SE, respectively. In binding assays, LMR-101 primarily inhibited tert -[ 35 S] butylbicyclophosphorothionate binding to γ-aminobutyric acid type A (GABA A ) receptors (half-maximal inhibitory concentration = 2.06 μmol·L –1 ), but it did not affect [ 3 H] flunitrazepam or [ 3 H] muscimol binding. Significance It is anticipated that LMR-101 might play an essential role in the clinical management of epilepsy and SE. LMR-101 also might bind to a novel target site on the GABA A receptor that is different from existing antiepileptic drugs. Further study of the mechanisms of action of LMR-101 would be of considerable value in the search for new active drug sites on GABA A receptors.
研究领域:
神经科学
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药理学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2018
·
IF 3.04
Yuntao Ou,Man Su,Yong Ling,Qianqian Wei,Fei Pan,Jiejia Li,Jun-Xu Li,Qing Zhu
Sinomenine , a major bioactive ingredient isolated from traditional Chinese medicine Sinomenium acutum , has been reported to have analgesic effects in various pain animal models. N -demethylsinomenine, the N -demethylated product of sinomenine, has been identified to be the major metabolite of sinomenine and is also a natural component extracted from Sinomenium acutum . This study examined the anti-allodynic effects of N -demethylsinomenine in a mouse model of postoperative pain . A significant and sustained mechanical allodynia that lasted for 4 days was induced by making a surgical incision on the right hind paw in mice. Acute treatment with N -demethylsinomenine (10–40 mg/kg, s.c.) relieved the mechanical allodynia in a dose-dependent manner. Although there was no difference in maximal analgesic effect between N -demethylsinomenine (40 mg/kg, s.c.) and sinomenine (40 mg/kg, s.c.), the onset of action of N- demethylsinomenine was quicker than sinomenine. Repeated treatment with N- demethylsinomenine (10–40 mg/kg/day, s.c.) also dose-dependently exerted sustained antinociception against postoperative allodynia and did not produce analgesic tolerance and carry-over effect. The anti-allodynia induced by N -demethylsinomenine (40 mg/kg, s.c.) was attenuated by bicuculline , a selective γ-aminobutyric acid type A (GABA A ) receptor antagonist. In addition, the doses of N -demethylsinomenine used here did not alter the locomotor activity in mice. Our findings demonstrated that N -demethylsinomenine exerts behaviorally-specific anti-allodynia against postoperative allodynia mediated through the GABA A receptors, suggesting it may be a useful novel pharmacotherapy for the control of postoperative pain.
研究领域:
药理学
·
疼痛研究
·
神经科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MOLECULAR STRUCTURE
·
2025
·
IF 4.7
Mengjiao Li,Lina Hu,Shijia Yi,Hui Yan,Zheng Liu,Kang Lei,Xuekun Wang,Shiben Wang
In this paper, two series of triazolopyrimidines derivatives were designed, synthesized, and all the target compounds were structurally confirmed using 1 H NMR, 13 C NMR and HRMS methods. Pharmacological experiments were carried out using maximal electroshock (MES), subcutaneous pentylenetetrazole (scPTZ) and rotating rod (ROT) models for activity and neurotoxicity screening, and potential compounds were screened out for further determination of ED 50 , TD 50 and in vitro binding experiments. Finally, compound 5,7-Bis(pentyloxy)-[1,2,4]triazolo[1,5-a]pyrimidine ( 6b ) with best activity and lowest toxicity was obtained. The pharmacological results showed that the ED 50 of compound 6b was MES = 11.3 mg/kg, PTZ = 9.5 mg/kg, which was superior to that of the carbamazepine (MES = 6.3 mg/kg) and ethosuximide (PTZ = 3.6 mg/kg). The IC 50 of compound 6b binding affinity toward the GABA A receptor was 0.15 µM, and the GABA content experiments showed that compound 6b significantly increased the GABA content in the rat brain. In elevated plus maze (EPM) assay, compound 6b possessed anxiolytic effects. In silico studies, most of the target compounds have suitable physicochemical and pharmacokinetic data with the possibility of drug-forming properties, molecular docking results showed that compound 6b could generate more interactions with the amino acid residues of diazepam active site of GABA A receptor.
研究领域:
药理学
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药物化学
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神经科学
✓ 已验证
产品关联
DOI
高影响因子
Scientific Reports
·
2021
·Vol. 11
·期 1
·1-9
·
IF 4.38
Zhou Zhiyong,Qiu Nanqing,Ou Yuntao,Wei Qianqian,Tang Wenting,Zheng Mingcong,Xing Yaluan,Li Jie-Jia,Ling Yong,Li Junxu,Zhu Qing
Chronic pain is a significant public health problem that afflicts nearly 30% of the global population, but current pharmacotherapies are insufficient. Previous report indicated that N -demethylsinomenine, an active metabolite of sinomenine, is efficacious against postoperative pain. The present study investigated whether N -demethylsinomenine is effective for chronic painful conditions or whether repeated treatment alters its effect. Both chronic constriction injury (CCI) surgery and complete Freund’s adjuvant (CFA) intraplantar injection induced significant and reliable mechanical allodynia at least for 7 days. Acute treatment with N -demethylsinomenine (10–40 mg/kg, i.p.) dose-dependently attenuated the mechanical allodynia both in CCI-induced neuropathic pain and CFA-induced inflammatory pain in mice. The potency of N -demethylsinomenine for reducing CFA-induced mechanical allodynia was slightly higher than sinomenine. During the period of repeated treatment, N -demethylsinomenine maintained its anti-allodynic effect against both neuropathic and inflammatory pain without producing carry-over effect. Pretreatment with bicuculline, a selective γ-aminobutyric acid type A (GABA A ) receptor antagonist, almost completely blocked the anti-allodynia of N -demethylsinomenine (40 mg/kg) both in CCI and CFA-treated mice. Our findings indicated that N -demethylsinomenine exhibits GABA A receptor-mediated anti-allodynic effects in mouse models of neuropathic and inflammatory pain, suggesting it may be a useful novel pharmacotherapy for the control of chronic pain.
研究领域:
药理学
·
疼痛研究
·
神经科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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