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排序方式: 共有195条查询结果,搜索用时 15 毫秒
101.
Cristina Martín-Escura Alicia Medina-Peris Luke A. Spear Roberto de la Torre Martínez Luis A. Olivos-Or María Victoria Barahona Sara Gonzlez-Rodríguez Gregorio Fernndez-Ballester Asia Fernndez-Carvajal Antonio R. Artalejo Antonio Ferrer-Montiel Rosario Gonzlez-Muiz 《International journal of molecular sciences》2022,23(5)
Transient receptor potential melastatin subtype 8 (TRPM8) is a cation channel extensively expressed in sensory neurons and implicated in different painful states. However, the effectiveness of TRPM8 modulators for pain relief is still a matter of discussion, since structurally diverse modulators lead to different results, depending on the animal pain model. In this work, we described the antinociceptive activity of a β–lactam derivative, RGM8-51, showing good TRPM8 antagonist activity, and selectivity against related thermoTRP channels and other pain-mediating receptors. In primary cultures of rat dorsal root ganglion (DRG) neurons, RGM8-51 potently reduced menthol-evoked neuronal firing without affecting the major ion conductances responsible for action potential generation. This compound has in vivo antinociceptive activity in response to cold, in a mouse model of oxaliplatin-induced peripheral neuropathy. In addition, it reduces cold, mechanical and heat hypersensitivity in a rat model of neuropathic pain arising after chronic constriction of the sciatic nerve. Furthermore, RGM8-51 exhibits mechanical hypersensitivity-relieving activity, in a mouse model of NTG-induced hyperesthesia. Taken together, these preclinical results substantiate that this TRPM8 antagonist is a promising pharmacological tool to study TRPM8-related diseases. 相似文献
102.
Carlotta Bon Ting-Rong Chern Elena Cichero Terrence E. OBrien Stefano Gustincich Raul R. Gainetdinov Stefano Espinoza 《International journal of molecular sciences》2022,23(6)
Trace amine-associated receptor 5 (TAAR5) is a G protein-coupled receptor that belongs to the TAARs family (TAAR1-TAAR9). TAAR5 is expressed in the olfactory epithelium and is responsible for sensing 3-methylamine (TMA). However, recent studies showed that TAAR5 is also expressed in the limbic brain regions and is involved in the regulation of emotional behaviour and adult neurogenesis, suggesting that TAAR5 antagonism may represent a novel therapeutic strategy for anxiety and depression. We used the AtomNet® model, the first deep learning neural network for structure-based drug discovery, to identify putative TAAR5 ligands and tested them in an in vitro BRET assay. We found two mTAAR5 antagonists with low to submicromolar activity that are able to inhibit the cAMP production induced by TMA. Moreover, these two compounds also inhibited the mTAAR5 downstream signalling, such as the phosphorylation of CREB and ERK. These two hits exhibit drug-like properties and could be used to further develop more potent TAAR5 ligands with putative anxiolytic and antidepressant activity. 相似文献
103.
利用拮抗菌常温保鲜凤凰水蜜桃效果系统研究 总被引:2,自引:0,他引:2
由于使用化学保鲜剂对环境和人体存在危害,故观测和比较了两种病原菌拮抗菌——罗伦隐球酵母(Cryptococcus laurentii)和枯草芽孢杆菌(Bacillus subtilis)单独使用和与化学试剂(2%NaHCO3)配合使用对张家港市凤凰水蜜桃(Prunus persica)采后保鲜品质的影响。实验采取直接浸果的方式,果实处理后装入保鲜袋置于常温条件下(25℃),放置5d后测量其失重率、腐烂程度、硬度、可溶性固形物含量、呼吸强度、相对电导率、丙二醛(MDA)含量和多酚氧化酶(PPO)含量8种生理指标。结果表明:单独使用拮抗菌液的处理组果实保鲜效果最佳,其中枯草芽孢杆菌效果尤为显著;单独使用化学试剂处理组保鲜效果最差,二者结合处理组的效果居中。因此,对凤凰水蜜桃而言,拮抗菌制剂是比化学试剂NaHCO3更为有效且无污染的生物保鲜剂,适宜推广应用。 相似文献
104.
J. G. Millar M. Giblin D. Barton D. A. Reynard G. B. Neill E. W. Underhill 《Journal of chemical ecology》1990,16(12):3393-3409
Two sex pheromone components, 3(Z),6(Z),9(Z)-nonadecatriene (3Z,6Z,9Z-19 H), and 3(Z),6(Z),9(Z)-eicosatriene (3Z,6Z,9Z-20 H), have been positively identified, and a third component, 6(Z),9(Z)-nonadecadiene (6(Z),9(Z)-19 H) has been tentatively identified from abdominal tip extracts of female spring cankerworm moths,Paleacrita vernata Peck (Lepidoptera Geometridae). The pheromone components were identified by a combination of gas chromatography, electroantennography, mass spectrometry, chemical tests, comparison with standards, and field testing. Only 3Z,6Z,9Z-20 H exhibited significant attractant activity when tested alone, and it was potentiated by the other two components. The attractive blend was an 821 ratio of 3Z,6Z,9Z-20H/3Z,6Z,9Z-19H/6Z,9Z-19H. However, the two-component blend of 3Z,6Z,9Z-20 H and 6Z,9Z-19 H (81 ratio) was as attractive as the three-component blend in further field tests. A series of related compounds, the diene monoepoxides available from epoxidation of C19 and C20 3Z,6Z,9Z-trienes, some of which have been found in the pheromone blends of other moth species, were tested as behavioral antagonists. The attraction of male moths to synthetic lures was suppressed by the addition of 6Z,9Z-cis-3,4-epoxy-nonadecadiene to the lures. Additional experiments were performed to determine the effects of lure dosage, trap height, and trap design on the numbers of male moths captured.Issued as NRCC 30711. 相似文献
105.
1 INTRODUCTIONNuclear medicine is rapidly establishing itself as an wtortant tool in the in vivostudy of brain neuroCheAnstry. In particular, several radioligands for the dopaAnne DZreceptor have been developed and these have offered vocable new insights into the roleof dopathene in disorders of the locomotor fUllction, psychiatry and genetic disease.Epidepride, S-(-)-N-[(1-ethyl-2-pyrrolidinylis a potential dopaAnne DZ antagonist. It has high ~ity (Kd=24pmol/L) for theDZ receptor a… 相似文献
106.
Angel M. Cuesta Eunate Gallardo-Vara Juan Casado-Vela Lucía Recio-Poveda Luisa-María Botella Virginia Albiana 《International journal of molecular sciences》2022,23(8)
Rare Diseases (RD) are defined by their prevalence in less than 5 in 10,000 of the general population. Considered individually, each RD may seem insignificant, but together they add up to more than 7000 different diseases. Research in RD is not attractive for pharmaceutical companies since it is unlikely to recover development costs for medicines aimed to small numbers of patients. Since most of these diseases are life threatening, this fact underscores the urgent need for treatments. Drug repurposing consists of identifying new uses for approved drugs outside the scope of the original medical indication. It is an alternative option in drug development and represents a viable and risk-managed strategy to develop for RDs. In 2008, the “off label” therapeutic benefits of propranolol were described in the benign tumor Infantile Hemangioma. Propranolol, initially prescribed for high blood pressure, irregular heart rate, essential tremor, and anxiety, has, in the last decade, shown increasing evidence of its antiangiogenic, pro-apoptotic, vasoconstrictor and anti-inflammatory properties in different RDs, including vascular or oncological pathologies. This review highlights the finished and ongoing trials in which propranolol has arisen as a good repurposing drug for improving the health condition in RDs. 相似文献
107.
Pradeep Paudel Dong Hyun Kim Jieun Jeon Se Eun Park Su Hui Seong Hyun Ah Jung Jae Sue Choi 《International journal of molecular sciences》2021,22(7)
Traditional Chinese medicines (TCMs) have been a rich source of novel drug discovery, and Cassia seed is one of the common TCMs with numerous biological effects. Based on the existing reports on neuroprotection by Cassia seed extract, the present study aims to search possible pharmacological targets behind the neuroprotective effects of the Cassia seeds by evaluating the functional effect of specific Cassia compounds on various G-protein-coupled receptors. Among the four test compounds (cassiaside, rubrofusarin gentiobioside, aurantio-obtusin, and 2-hydroxyemodin 1-methylether), only aurantio-obtusin demonstrated a specific V1AR antagonist effect (71.80 ± 6.0% inhibition at 100 µM) and yielded an IC50 value of 67.70 ± 2.41 μM. A molecular docking study predicted an additional interaction of the hydroxyl group at C6 and a methoxy group at C7 of aurantio-obtusin with the Ser341 residue as functional for the observed antagonist effect. In the transient brain ischemia/reperfusion injury C57BL/6 mice model, aurantio-obtusin attenuated the latency time that was reduced in the bilateral common carotid artery occlusion (BCCAO) groups. Likewise, compared to neuronal damage in the BCCAO groups, treatment with aurantio-obtusin (10 mg/kg, p.o.) significantly reduced the severity of damage in medial cornu ammonis 1 (mCA1), dorsal CA1, and cortex regions. Overall, the findings of this study highlight V1AR as a possible target of aurantio-obtusin for neuroprotection. 相似文献
108.
米糠蛋白酶解物类阿片拮抗活性的研究 总被引:4,自引:0,他引:4
采用水解度(DH)对酶解米糠蛋白进行了研究,比较六种蛋白酶对米糠可溶性蛋白的水解作用,结果发现胰蛋白酶对米糠可溶性蛋白的水解作用最强,它的最适作用条件为:pH8.0,温度为37℃,[E]/[S]为12.5usp-u/kg。采用离体豚鼠回肠(GPI)检定法测定上述酶解物的类阿片拮抗活性,结果发现胰蛋白酶水解产物具有明显的类阿片拮抗活性,DH为11.9%时,其水解产物(样品A)的类阿片拮抗活性最高。体积排阻高效液相色谱测定它的相对分子质量分布范围在125-24233Da之间。 相似文献
109.
醛固酮是肾上腺皮质产生的一种盐皮质激素,主要作用于肾小球远曲小管和集合管,促进钠的重吸收和钾的分泌。醛固酮可促进炎症反应,导致心肌重构和纤维化。醛固酮通过盐皮质激素受体(MR)起作用,MR主要在心脏、肾脏和血管中表达。MR过度活化,可引起内皮功能障碍、纤溶紊乱、氧化应激和心血管、肾脏纤维化,最终导致器官损伤、功能障碍甚至衰竭。盐皮质激素受体拮抗剂(MRA)可通过抑制MR激活引起的炎症和纤维化达到心肾保护作用。新型非甾体类MRA非奈利酮以其高选择性、有效阻断MR,带来了确切的心肾保护作用。 相似文献
110.
Four conditional responses (CRs) were measured in rats implanted with bilateral cannulas in the basolateral nuclear complex of the amygdala (BLA). During retention testing in either the original training context or a shifted context, BLA was infused with artificial cerebral spinal fluid (ACSF) or ACSF containing an N-methyl-D-aspartate receptor antagonist (APV). Regardless of the testing context, APV infusion into BLA completely blocked the expression of conditional eyeblink facilitation and significantly attenuated the expression of conditional freezing, ultrasonic vocalization, and defecation. Discriminant analysis found eyeblink facilitation to be comparable to freezing in predicting group membership (APV vs. ACSF) and both to be better predictors than the other two CRs. The APV effect did not depend on the exact cannula positions within BLA. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献