forced swim

L-701324 是一种 NMDA 受体，对甘氨酸位点具有高亲和力和选择性，用作口服活性和长效抗惊厥药。

Antidepressant agent 9 (Compound 24) 是一种具备口服活性并能穿透血脑屏障的NMDAR和SERT抑制剂，IC50分别为3.50 μM和1044 nM。该化合物展现出优良的代谢稳定性和血浆暴露水平。此外，Antidepressant agent 9 在小鼠强迫游泳试验中表现出抗抑郁样活性。

Mecamylamine hydrochloride (Mevasin) 是一种易穿过血脑屏障的烟碱拮抗剂，用作高血压的神经节阻滞剂，具有抗神经疾病作用。

Urocortin III is a neuropeptide hormone and member of the corticotropin-releasing factor (CRF) family which includes mammalian CRF , urocortin , urocortin II , frog sauvagine, and piscine urotensin I.1 Human urocortin III shares 90, 40, 37, and 21% identity to mouse urocortin III , mouse urocortin II , human urocortin , and mouse urocortin, respectively. Urocortin III selectively binds to type 2 CRF receptors (Kis = 21.7, 13.5, and >100 nM for rat CRF2α, rat CRF2β, and human CRF1, respectively). It stimulates cAMP production in CHO cells expressing rat CRF2α and mouse CRF2β (EC50s = 0.16 and 0.12 nM, respectively) as well as cultured anterior pituitary cells expressing endogenous CRF2β. Urocortin III is co-released with insulin to potentiate glucose-stimulated somatostatin release in vitro in human pancreatic β-cells.2 In vivo, urocortin III reduces food intake in a dose- and time-dependent manner in mice with a minimum effective dose (MED) of 0.3 nmol/animal.3 It increases swimming time in a forced swim test in mice, indicating antidepressant-like activity.4References1. Lewis, K., Li, C., Perrin, M.H., et al. Identification of urocortin III, an additional member of the corticotropin-releasing factor (CRF) family with high affinity for the CRF2 receptor. Proc. Natl. Acad. Sci. U.S.A. 98(13), 7570-7575 (2001).2. van der Meulen, T., Donaldson, C.J., Cáceres, E., et al. Urocortin3 mediates somatostatin-dependent negative feedback control of insulin secretion. Nat. Med. 21(7), 769-776 (2015).3. Pelleymounter, M.A., Joppa, M., Ling, N., et al. Behavioral and neuroendocrine effects of the selective CRF2 receptor agonists urocortin II and urocortin III. Peptides 25(4), 659-666 (2004).4. Tanaka, M., Kádár, K., Tóth, G., et al. Antidepressant-like effects of urocortin 3 fragments. Brain Res. Bull. 84(6), 414-418 (2011). Urocortin III is a neuropeptide hormone and member of the corticotropin-releasing factor (CRF) family which includes mammalian CRF , urocortin , urocortin II , frog sauvagine, and piscine urotensin I.1 Human urocortin III shares 90, 40, 37, and 21% identity to mouse urocortin III , mouse urocortin II , human urocortin , and mouse urocortin, respectively. Urocortin III selectively binds to type 2 CRF receptors (Kis = 21.7, 13.5, and >100 nM for rat CRF2α, rat CRF2β, and human CRF1, respectively). It stimulates cAMP production in CHO cells expressing rat CRF2α and mouse CRF2β (EC50s = 0.16 and 0.12 nM, respectively) as well as cultured anterior pituitary cells expressing endogenous CRF2β. Urocortin III is co-released with insulin to potentiate glucose-stimulated somatostatin release in vitro in human pancreatic β-cells.2 In vivo, urocortin III reduces food intake in a dose- and time-dependent manner in mice with a minimum effective dose (MED) of 0.3 nmol/animal.3 It increases swimming time in a forced swim test in mice, indicating antidepressant-like activity.4 References1. Lewis, K., Li, C., Perrin, M.H., et al. Identification of urocortin III, an additional member of the corticotropin-releasing factor (CRF) family with high affinity for the CRF2 receptor. Proc. Natl. Acad. Sci. U.S.A. 98(13), 7570-7575 (2001).2. van der Meulen, T., Donaldson, C.J., Cáceres, E., et al. Urocortin3 mediates somatostatin-dependent negative feedback control of insulin secretion. Nat. Med. 21(7), 769-776 (2015).3. Pelleymounter, M.A., Joppa, M., Ling, N., et al. Behavioral and neuroendocrine effects of the selective CRF2 receptor agonists urocortin II and urocortin III. Peptides 25(4), 659-666 (2004).4. Tanaka, M., Kádár, K., Tóth, G., et al. Antidepressant-like effects of urocortin 3 fragments. Brain Res. Bull. 84(6), 414-418 (2011).

Alaproclate is a selective serotonin reuptake inhibitor (SSRI).1,2 It inhibits depletion of serotonin (5-HT) induced by 4-methyl-α-ethyl-m-tyramine in rat cerebral cortex, hippocampus, hypothalamus, and striatum (EC50s = 18, 4, 8, and 12 mg kg, respectively).1 Alaproclate inhibits NMDA-evoked currents and depolarization-induced voltage-dependent potassium currents in rat hippocampal neurons (IC50s = 1.1 and 6.9 μM, respectively) and does not inhibit GABA-evoked currents when used at concentrations up to 100 μM.2 It increases sirtuin 1 (SIRT1) levels in N2a murine neuroblastoma cells expressing apolipoprotein E4 (ApoE4; IC50 = 2.3 μM) and in the hippocampus in the FXFAD-ApoE4 transgenic mouse model of Alzheimer's disease when administered at a dose of 20 mg kg twice daily.3 Alaproclate (40 mg kg) decreases immobility time in the forced swim test in rats, indicating antidepressant-like activity.4References1. Michael, G.B., Eidam, C., Kadlec, K., et al. Increased MICs of gamithromycin and tildipirosin in the presence of the genes erm(42) and msr(E)-mph(E) for bovine Pasteurella multocida and Mannheimia haemolytica. Journal of Antimicrobial Chemotherapy 67(6), 1555-1557 (2012).2. Svensson, B.E., Werkman, T.R., and Rogawski, M.A. Alaproclate effects on voltage-dependent K+ channels and NMDA receptors: Studies in cultured rat hippocampal neurons and fibroblast cells transformed with Kv1.2 K+ channel cDNA. Neuropharmacology 33(6), 795-804 (1994).3. Campagna, J., Soilman, P., Jagodzinska, B., et al. A small molecule ApoE4-targeted therapeutic candidate that normalizes sirtuin 1 levels and improves cognition in an Alzheimer's disease mouse model. Sci. Rep. 8(1), 17574 (2018).4. Danysz, W.P., A., Kostowski, W., Malatynska, E., et al. Comparison of desipramine, amitriptyline, zimeldine and alaproclate in six animal models used to investigate antidepressant drugs. Pharmacol. Toxicol. 62(1), 42-50 (1988). Alaproclate is a selective serotonin reuptake inhibitor (SSRI).1,2 It inhibits depletion of serotonin (5-HT) induced by 4-methyl-α-ethyl-m-tyramine in rat cerebral cortex, hippocampus, hypothalamus, and striatum (EC50s = 18, 4, 8, and 12 mg kg, respectively).1 Alaproclate inhibits NMDA-evoked currents and depolarization-induced voltage-dependent potassium currents in rat hippocampal neurons (IC50s = 1.1 and 6.9 μM, respectively) and does not inhibit GABA-evoked currents when used at concentrations up to 100 μM.2 It increases sirtuin 1 (SIRT1) levels in N2a murine neuroblastoma cells expressing apolipoprotein E4 (ApoE4; IC50 = 2.3 μM) and in the hippocampus in the FXFAD-ApoE4 transgenic mouse model of Alzheimer's disease when administered at a dose of 20 mg kg twice daily.3 Alaproclate (40 mg kg) decreases immobility time in the forced swim test in rats, indicating antidepressant-like activity.4 References1. Michael, G.B., Eidam, C., Kadlec, K., et al. Increased MICs of gamithromycin and tildipirosin in the presence of the genes erm(42) and msr(E)-mph(E) for bovine Pasteurella multocida and Mannheimia haemolytica. Journal of Antimicrobial Chemotherapy 67(6), 1555-1557 (2012).2. Svensson, B.E., Werkman, T.R., and Rogawski, M.A. Alaproclate effects on voltage-dependent K+ channels and NMDA receptors: Studies in cultured rat hippocampal neurons and fibroblast cells transformed with Kv1.2 K+ channel cDNA. Neuropharmacology 33(6), 795-804 (1994).3. Campagna, J., Soilman, P., Jagodzinska, B., et al. A small molecule ApoE4-targeted therapeutic candidate that normalizes sirtuin 1 levels and improves cognition in an Alzheimer's disease mouse model. Sci. Rep. 8(1), 17574 (2018).4. Danysz, W.P., A., Kostowski, W., Malatynska, E., et al. Comparison of desipramine, amitriptyline, zimeldine and alaproclate in six animal models used to investigate antidepressant drugs. Pharmacol. Toxicol. 62(1), 42-50 (1988).

5α-Androst-16-en-3α-ol is a steroid pheromone that has been found in boar testes and human male axillary sweat and has diverse biological activities.1,2It enhances GABA-activated currents in primary mouse cerebellar granule cells (EC50= 0.4 μM).25α-Androst-16-en-3α-ol (0.1-1 μM) increases the amplitude of GABA-activated currents in HEK293 cells expressing human α1β2γ2and α2β2γ2subunit-containing GABAAreceptors.In vivo, 5α-androst-16-en-3α-ol (5-10 mg kg) decreases immobility time in the forced swim test in mice. It increases time spent in the open arms of the elevated plus maze in mice, indicating anxiolytic-like activity, when administered at doses ranging from 30 to 50 mg kg. 5α-Androst-16-en-3α-ol protects against seizures induced by pentylenetetrazole or electroshock in mice (ED50s = 48.9 and 21.9 mg kg, respectively). 1.Brooksbank, B.W., Brown, R., and Gustafsson, J.A.The detection of 5α-androst-16-en-3α-ol in human male axillary sweatExperientia30(8)864-865(1974) 2.Kaminski, R.M., Marini, H., Ortinski, P.I., et al.The pheromone androstenol (5α-androst-16-en-3α-ol) is a neurosteroid positive modulator of GABAA receptorsJ. Pharmacol. Exp. Ther.317(2)694-703(2006)

Galanin (2-11) amide is a synthetic peptide fragment of the neuropeptide galanin and an agonist of the galanin-2 (GAL2) receptor (EC50= 9.32 nM in a fluorescence imaging plate reader assay).1It selectively binds to the GAL2receptor (IC50= 1.76 nM for the rat receptor) over the GAL1receptor (IC50= 879 nM for the human receptor) but does also bind to the GAL3receptor (Ki= 271 nM for the rat receptor).1,2Intracerebroventricular administration of galanin (2-11) amide (1 nmol/animal) decreases immobility in the forced swim test in rats.3It also reduces the hind paw mechanical pain threshold and increases the hind paw cold sensitivity threshold in rats.1

High affinity corticotropin releasing factor receptor1 (CRF1) antagonist (Ki = 3.5 nM). Reduces stress-induced elevations of plasma ACTH. Anxiolytic and antidepressant in vivo. Orally bioavailable. Chen and Grigoriadis (2005) NBI 30775 (R121919), an orally active antagonist of the corticotropin-releasing factor (CRF) type-1 receptor for the treatment of anxiety and depression. Drug Dev.Res. 65 216 |Jutkiewicz et al (2005) The effects of CRF antagonists, antalarmin, CP154,526, LWH234, and R121919, in the forced swim test and on swim-induced increases in adrenocorticotropin in rats. Psychopharmacology (Berl). 180 215 PMID:15696320 |Gutman et al (2003) The corticotropin-releasing factor1 receptor antagonist R121919 attenuates the behavioral and endocrine responses to stress. J.Pharmacol.Exp.Ther. 304 874 PMID:12538845 |Heinrichs et al (2002) Brain penetrance, receptor occupancy and antistress in vivo efficacy of a small molecule cortico. releasing factor type I receptor selective antagonist. Neuropsychopharmacology 27 194 PMID:12093593

Tianeptine metabolite MC5是一种来自非典型抗抑郁化合物tianeptine的活性代谢物，通过β-氧化形成。此代谢物在使用表达人类μ-阿片受体（MOR）而非人类δ-阿片受体（DOR；EC50s = 0.454和 >100 µM, 分别）的HEK293T细胞进行的生物发光共振能量转移(BRET)试验中，特异性诱导G蛋白激活。在野生型小鼠上，30 mg/kg剂量的Tianeptine metabolite MC5可减少强迫游泳测试中的静止时间，但在MOR敲除小鼠中则不会，表明其具有MOR依赖的抗抑郁样活性。

TIP39作为一种神经肽及甲状旁腺激素受体2型(PTH2R)激动剂，在表达重组人或大鼠PTH2R的COS-7细胞中诱导cAMP积累（EC50分别为0.5和0.8 nM），以及在内源性表达PTH2R的F-11细胞中（EC50 = 1.15 nM）。在CFK2大鼠软骨细胞中，TIP39 (1 nM)诱导细胞周期在G0/G1阶段停滞，并减少软骨分化的主要调控因子Sox9的表达。此外，TIP39 (100 pmol/动物)在小鼠强迫游泳测试中减少了不动时间。

Tricin 7-O-glucoside是一种天然的黄酮，具有抗抑郁和抗焦虑作用，增加小鼠在强迫游泳试验中的活动时间。通过减轻脑 I R 损伤和减弱血脑屏障 (BBB) 的破坏来保护大脑，降低HMGB1 和 NF-κB 信号通路。