5-HT_1A Receptor ( Ki = 3.4 nM )
F-15599 is a selective agonist at 5-HT_1A receptors (Ki = 0.8 nM for rat 5-HT_1A receptors). It shows >100-fold selectivity over 5-HT_1B, 5-HT_1D, 5-HT_2A, 5-HT_2C, D₁, D₂, and α₁-adrenoceptors. It exhibits biased agonism toward G_i protein signaling and preferentially activates postsynaptic 5-HT_1A receptors. [3]

F-15599 (NLX-101)在放射性配体结合实验中显示对5-HT1A受体的选择性比其他血清素受体亚型高100倍[3]。
显示偏向性激动特征，优先激活Gαi/o而非β-arrestin信号通路[2]。

F15599（0.06 或 0.12 mg/kg）显着降低 l-DOPA 诱导的运动障碍 (LID)，而不影响大鼠的运动表现。 F15599高剂量30 μg/μL治疗的大鼠表现出较少的LID和轻微的5-HT综合征[1]。 F15599（0.0625、0.125、0.25、0.5 和 1.0 mg/kg，i,p）导致攻击潜伏期显着且剂量依赖性（MED = 0.125 mg/kg）延迟，并有效降低（ID50 = 0.095 mg/kg）针对入侵大鼠的攻击行为量。从 0.25 mg/kg 剂量开始，F15599 会诱发所谓的血清素综合征的明显症状，其特征是扁平身体姿势、摇头、下唇缩回和后肢外展，导致行为不活动得分增加和社交脱离[2]。 F15599 使内侧前额叶皮层 (mPFC) 锥体神经元的放电率从 0.2 µg/kg iv 增加，并在剂量 >10 倍时降低中缝背侧 5-羟色胺能神经元的放电率（最小有效剂量 8.2 µg/kg iv）。 F15599 增加 mPFC 中的多巴胺输出（依赖于突触后 5-HT1A 受体激活的效应），腹腔注射 ED50 为 30 µg/kg，同时减少海马 5-HT 释放（完全依赖于 5-HT1A 自身受体激活的效应） ED50 为 240 µg/kg ip[3]。

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F-15599（0.16 mg/kg 皮下注射）使大鼠前额叶皮层多巴胺水平增加 200%，同时降低背侧中缝核的血清素水平，证实其优先作用于突触后受体。该效应可被 5-HT_1A 拮抗剂 WAY100635 阻断。 [3]

在攻击行为大鼠模型（居住者-入侵者测试）中，F-15599（0.04–0.63 mg/kg 皮下注射）在 0.16 mg/kg 剂量下显著减少攻击持续时间和频率。该抗攻击效应可被 WAY100635 逆转，表明由 5-HT_1A 受体介导。 [2]

F-15599（0.0025–0.04 mg/kg 静脉注射）可诱导大鼠下唇收缩（LLR）和扁平体姿（FBP），但其对突触后反应（ED₅₀ = 0.005 mg/kg）的效力是突触前效应（ED₅₀ = 0.016 mg/kg）的 3 倍。 [3]

In summary, this model involves housing male rats alone in sizable observation cages measuring 80 × 55 × 50 cm, along with an oviduct-ligated female, to prevent social isolation and promote sexual behavior, which in turn encourages territorial behavior. A baseline level of aggressive and offensive behavior is assessed after a week, three days in a row, during a maximum 10-minute confrontation with a male conspecific who is not known to the subject (WTG rats). About 60 minutes before the start of this social provocation test, the female partner of the experimental rat is taken out of the home observation cage. As conspecific intruder animals, naive male WTG rats (average weight 372 ± 9.5 g, 3.5–4 months old) are socially housed in groups of three in transparent Makrolon type IV cages. The intruder is eliminated during the first three tests as soon as the resident launches their first complete attack, and the attack latency time (ALT) is recorded. The fourth baseline test, which is conducted on day 4, records and analyzes the entire spectrum of behaviors. Based on the ALT and the degree of offensive behavior, the experimental groups are matched. The experimental groups contain only animals that have attacked (ALT <600 s). Eleven of the fourteen4 participants in the study are not attackers. The following day, day 5, the experimental vehicle (sterile Ultra Pure water, n = 19 and n = 20) or F15599 (0.0625, 0.125, 0.25, 0.5 and 1.0 mg/kg, IP, experiment 1, n = 45) or F13714 (0.003, 0.006, 0.012, 0.025, 0.062, 0.125, 0.250, IP, experiment 2, n = 50) are given 30 minutes prior to the 10-minute confrontation with a drug-free unfamiliar intruder conspecific, and their behavior is recorded once more. In addition, animals are tested in experiment 3 thirty minutes after treatment with vehicle/vehicle (UP), vehicle/F15599 (0.1 mg/kg) or F13714, or vehicle/WAY-100635 (0.3 mg/kg) or vehicle or WAY100635 (0.3 mg/kg)/F15599 (0.1 mg/kg) or F13714. There are 6–8 subjects in each treatment group, for a total of 41 creatures.

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For aggression studies, F-15599 was dissolved in saline and administered subcutaneously (s.c.) at doses of 0.04, 0.16, and 0.63 mg/kg 30 minutes before behavioral testing. Control groups received saline. [2]

For neurochemical and behavioral assays, F-15599 was injected intravenously (i.v.) at 0.0025–0.04 mg/kg or subcutaneously at 0.16 mg/kg. WAY100635 (0.16 mg/kg s.c.) was administered 20 minutes prior to F-15599 for antagonism tests. [3]

[1]. Characterizing the differential roles of striatal 5-HT1A auto- and hetero-receptors in the reduction of l-DOPA-induced dyskinesia. Exp Neurol. 2017 Jun;292:168-178.

[2]. Anti-aggressive effects of the selective high-efficacy 'biased' 5-HT?A receptor agonists F15599 and F13714 in male WTG rats. Psychopharmacology (Berl). 2016 Mar;233(6):937-47.

[3]. Preferential in vivo action of F15599, a novel 5-HT(1A) receptor agonist, at postsynaptic 5-HT(1A) receptors. Br J Pharmacol. 2010 Aug;160(8):1929-40.

F-15599 is a high-efficacy "biased agonist" that preferentially targets cortical postsynaptic 5-HT_1A receptors over somatodendritic autoreceptors, enhancing frontal cortex dopamine release. This contrasts with classical 5-HT_1A agonists like 8-OH-DPAT. [3]

Its anti-aggressive effects are mediated via postsynaptic 5-HT_1A receptors in corticolimbic regions, suggesting therapeutic potential for impulse control disorders. [2]
First-in-class biased agonist with preferential postsynaptic activity, developed for neuropsychiatric disorders [3].

C19H21CLF2N4O

394.85

394.137

C, 57.80; H, 5.36; Cl, 8.98; F, 9.62; N, 14.19; O, 4.05

635323-95-4

635323-95-4; 955112-72-8; 635323-96-5 (fumarate)

11741361

White to off-white solid powder

3.64

58.12

1

6

5

27

496

0

ClC1=C(C([H])=C([H])C(=C1[H])C(N1C([H])([H])C([H])([H])C(C([H])([H])N([H])C([H])([H])C2N=C([H])C(C([H])([H])[H])=C([H])N=2)(C([H])([H])C1([H])[H])F)=O)F

WAAXKNFGOFTGLP-UHFFFAOYSA-N

InChI=1S/C19H21ClF2N4O/c1-13-9-24-17(25-10-13)11-23-12-19(22)4-6-26(7-5-19)18(27)14-2-3-16(21)15(20)8-14/h2-3,8-10,23H,4-7,11-12H2,1H3

(3-chloro-4-fluorophenyl)-[4-fluoro-4-[[(5-methylpyrimidin-2-yl)methylamino]methyl]piperidin-1-yl]methanone

NLX-101; NLX 101; 635323-95-4; F-15,599; (3-Chloro-4-fluorophenyl)(4-fluoro-4-((((5-methylpyrimidin-2-yl)methyl)amino)methyl)piperidin-1-yl)methanone; UNII-83481Y1YCX; 4-Piperidinemethanamine, 1-(3-chloro-4-fluorobenzoyl)-4-fluoro-N-((5-methyl-2-pyrimidinyl)methyl)-; 83481Y1YCX; F-15,599; NLX101; F-15,599; F 15,599; F15,599; F15599

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

注意： 本产品在运输和储存过程中需避光。

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO: ~250 mg/mL (~633.2 mM)
Ethanol: ~79 mg/mL

配方 1 中的溶解度: ≥ 2.17 mg/mL (5.50 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 21.7 mg/mL澄清DMSO储备液加入400 μL PEG300中，混匀；然后向上述溶液中加入50 μL Tween-80，混匀；加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 2 中的溶解度: ≥ 2.17 mg/mL (5.50 mM) (饱和度未知) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 21.7 mg/mL澄清DMSO储备液加入900 μL 20% SBE-β-CD生理盐水溶液中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

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配方 3 中的溶解度: ≥ 2.17 mg/mL (5.50 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 21.7 mg/mL 澄清 DMSO 储备液加入到 900 μL 玉米油中并混合均匀。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。