D3 receptor ( EC50 = 0.64 nM )

体外活性：PD-128907 HCl 是一种有效的选择性多巴胺 D3 受体激动剂，EC50 为 0.64 nM，选择性是多巴胺 D2 受体的 53 倍。当使用[ 3 H]螺哌隆作为CHOK1细胞中的放射性配体时，PD-128907对人D3受体(Ki，1nM)表现出对人D2受体(Ki，1183nM)约1000倍的选择性，并且对人D2受体(Ki，1183nM)表现出约10000倍的选择性。人类 D4 受体（Ki，7000 nM）。 PD 128907 用于研究这些受体在大脑中的作用，例如限制多巴胺进一步释放的抑制性自身受体。激酶测定： (+)-PD 128907 Hydrochloride 是一种选择性多巴胺 D2/D3 受体激动剂，人和大鼠 D3 受体的 Kis 分别为 1.7、0.84 nM，人和大鼠 D3 受体的 Kis 分别为 179、770 nM。

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在表达人D2或D3受体的转染细胞系中，通过掺入[3H]胸苷测量了一系列多巴胺激动剂增加有丝分裂的功能效力。激动剂的功能选择性与其结合选择性明显不同。（+）结合研究中D3受体选择性最强的化合物7-OH-DPAT、普拉克索、奎宁和PD-128907在功能测试中D3受体的效力分别是D2受体的7、15、21和54倍。溴隐亭对D2受体显示出10倍的功能选择性。D3选择性激动剂的已知行为支持D3受体在运动抑制中的作用，在多巴胺激动剂治疗运动功能障碍时应考虑到这一点。[1]

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PD-128907[4a R，10 b R-（+）-反式-3,4,4a，10 b-四氢-4-正丙基2H，5H-[1]苯并吡喃并[4,3-b]1,4-恶嗪-9-醇。]，选择性多巴胺（DA）D3受体激动剂配体对人D3受体（Ki，1nM）的选择性约为人D2受体（Ki，1183nM）的1000倍，对使用[3H]螺珀酮作为CHO-K1细胞中的放射性配体的人D4受体（Ki,7000nM）的选择性为10000倍。[3H]PD-128907的研究表明，与CHO-K1细胞（CHO-K1-D3）中表达的人D3受体具有饱和、高亲和力的结合，平衡解离常数（Kd）为0.99 nM，结合密度（Bmax）为475 fmol/mg蛋白质。在相同条件下，表达人D2受体（CHO-K1-D2）的CHO-K1细胞没有明显的特异性结合。抑制[3H]PD 128907与参考DA试剂结合的效力的等级顺序与D3受体的报告值一致。这些结果表明，[3H]PD 128907是一种新的、高度选择性的D3受体配体，具有高比活性、高特异性结合和低非特异性结合，因此可用于进一步表征DA D3受体。[2]

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本研究确定了PD 128907[R-（+）-反式-3,4,4a，10b-四氢-4-丙基-2H，5H-[1]苯并吡喃并[4,3-b]-1,4-恶嗪-9-ol]的生化和药理作用，这是一种多巴胺（DA）受体激动剂，对人类D3受体有偏好。在转染的中国仓鼠卵巢细胞（CHO K1）中，PD-128907以双相方式置换[3H]螺吡喃酮，这最适合双位点模型，D2L受体的高亲和力位点和低亲和力位点的Ki值分别为20和6964 nM，D3受体的相应位点分别为1.43和413 nM。向D2L和D3中添加钠和GTP类似物Gpp（NH）p会导致化合物亲和力的适度降低，这暗示了激动剂型作用。在激动剂结合（[3H]N-0437）中，PD 128907对D3的选择性是D2L的18倍，与拮抗剂结合高亲和力位点时的选择性相似。PD-128907对D4.2受体仅表现出微弱的亲和力（Ki=169 nM）。未观察到对多种其他受体的显著亲和力。PD-128907在转染了D2L或D3受体的CHO p-5细胞中刺激细胞分裂（通过[3H]胸苷摄取测量），与D2L受体相比，其激活D3的效力高出约6.3倍[4]。

PD 128907 可有效减少正常大鼠和 γ-丁内酯 (GBL) 治疗大鼠的 DA 合成。 PD 128907（3 mg/kg）可降低可卡因过量的毒性，完全防止可卡因的惊厥和致命作用。这种保护通过与 D3 相关的机制发生，并且这种保护延伸到癫痫发作。

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多巴胺（DA）自身受体沿着中脑DA神经元的躯体化程度表达，调节冲动活动，而在DA神经末梢表达的多巴胺自身受体则调节DA的合成和释放。大量证据表明，这些DA自身受体是DA受体的D2亚型。然而，许多药理学研究表明DA D3受体具有自身受体作用。这种可能性是通过基因靶向缺乏D3受体的小鼠进行测试的。D3受体突变体和野生型小鼠黑质和腹侧被盖区DA神经元的基础放电率没有差异。假定的D3受体选择性激动剂R（+）-反式-3,4,4a，10b-四氢-4-丙基-2H，5H-（1）苯并吡喃（4,3-b）-1,4-恶嗪+++-9-ol（PD-128907）在抑制两组小鼠中脑DA神经元的活性方面是等效的。在DA自身受体功能的γ-丁内酯（GBL）模型中，突变型和野生型小鼠在纹状体DA合成及其被PD-128907抑制方面是相同的。腹侧纹状体DA释放的体内微透析研究显示，突变小鼠的细胞外DA基础水平较高，但PD 128907对突变和野生型小鼠的抑制作用相似。这些结果表明，PD-128907对多巴胺细胞功能的影响反映了D2受体的刺激，而不是D3受体的刺激。尽管D3受体似乎没有显著参与DA自身受体功能，但它们可能参与DA释放的突触后激活短环反馈调节。[3]

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在体内，该化合物在正常和γ-丁内酯（GBL）治疗的大鼠中均具有减少DA合成的活性；在GBL模型中，与D3受体表达较低的纹状体相比，D3表达较高的中脑边缘区的下降幅度更大。PD-128907降低了大鼠纹状体、伏隔核和内侧额叶皮层以及猴壳核中DA的释放（通过脑微透析测量）。从行为上讲，PD-128907在低剂量下降低了大鼠的自发运动活动（LMA），而在高剂量下观察到了刺激作用。高剂量的PD-128907与D1激动剂SKF 38393联合使用，逆转了利血平诱导的喉罩减少和诱导的立体型，表明了突触后DA激动剂的作用。目前尚不清楚DA受体的哪种亚型可能介导PD 128907的药理作用。然而，目前的研究结果表明，PD 128907显示出对DA D3的偏好，而不是D2L和D4.2受体，这表明它在低剂量下的作用可能是由于与D3受体的相互作用，在高剂量下，它可能与D2和D3受体都相互作用。[4]

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可卡因滥用是一个公共卫生问题，过量服用会导致癫痫发作和死亡。在本研究中，多巴胺D（3/）D（2）受体激动剂剂量依赖性地完全预防了可卡因的惊厥和致死作用。优选D（3）的激动剂R-（+）-反式-3,4a，10b-四氢-4-丙基-2H，5H-[1]苯并吡喃并[4,3-b]-1,4-恶嗪-9-ol）[（+）-PD-128907]，（+）-7-羟基二丙基氨基四氢萘，以及混合的D（3/）D（2）激动剂奎尼罗和奎洛烷都对小鼠可卡因毒性有效。这些化合物的抗惊厥作用发生在低于倒置筛查测试中评估的产生运动损伤的剂量时。（+）-PD 128907还赋予了对选择性多巴胺摄取抑制剂1-[2-[双（4-氟苯基）甲氧基]乙基]-4-[3-苯基-丙基]哌嗪（GBR 12909）惊厥作用的保护。（+）-PD-128907（3 mg/kg）对这些多巴胺能化合物的作用可能具有选择性，这可以通过其对通过其他神经机制起作用的多种惊厥药[戊四唑、（+）-荷包牡丹碱和苦味毒、4-氨基吡啶和叔丁基双甘膦酰硫代酯、N-甲基-d-天冬氨酸盐、红藻氨酸、毛果芸香碱、尼古丁、士的宁、氨茶碱、阈值电击和6-Hz电刺激]普遍缺乏保护作用来证明。直接和相关证据表明，这些作用是由D（3）受体介导的。D（3）受体拮抗剂[3-[4[1-（4-[2[4-（3-二乙氨基-丙氧基）-苯基]-苯并咪唑-l-基]-丁基）-1H-苯并咪唑-2-基]-苯氧基]-丙基）-二乙胺具有立体特异性和可逆性；PD 58491]但不包括D（2）受体[3[[4-（4-氯苯基）-4-羟基哌啶-1-基]甲基-1H-吲哚；L-741626。抗惊厥效力与D（3）受体功能测定中的效力呈正相关，但与D（2）受体功能无关。总之，这些发现表明，PD-128907预防可卡因抽搐和致死可能是由于D（3）受体介导的事件。[5]

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先前的研究结果表明，多巴胺D（3）/D（2）受体激动剂在急性施用可卡因的惊厥和致死作用中具有保护作用。这里提供的数据表明，保护是通过D（3）连接的机制发生的，并且保护范围扩展到癫痫发作点燃。D（3）拮抗剂SB-277011-A[4-喹啉甲酰胺，N-[反式-4-[2-（6-氰基-3,4-二氢-2（1H）-异喹啉基）乙基]-环己基]-（9CI）]阻止了D（3”/D（2）受体激动剂（+）-PD-128907[（R-（+）-反式-3,4a，10b-四氢-4-丙基-2H，5H-[1]苯并吡喃并[4,3-b]-1,4-恶嗪-9-ol）]对可卡因诱导的癫痫发作的抗惊厥作用。D（3）/D（2）激动剂（+）-PD-128907提供的保护在D（3”受体缺陷小鼠中被消除。在D（2）受体敲除小鼠中，（+）-PD-128907的抗惊厥作用得以保留。（+）-PD-128907还可以预防因每天重复服用60mg/kg可卡因而引起的可卡因引发的癫痫发作。（+）-PD-128907也阻断了由可卡因引发的小鼠癫痫发作。尽管反复服用可卡因可以提高可卡因产生癫痫发作和致死的效力（ED（50）值降低），但每天联合服用（+）-PD-128907可以显著防止这种效力变化。在每天服用可卡因和（+）-PD-128907的小鼠中，D（3）受体的密度增加，但亲和力没有增加。（+）-PD-128907对这种可卡因驱动的过程起作用的特异性得到了证明，（+）-PD-128907对GABA（a）受体拮抗剂戊四唑的癫痫发作没有显著影响。结合文献研究结果，数据表明多巴胺D（3）受体在启动抑制可卡因毒性作用的机制中起作用，这一发现可能与药物依赖、精神分裂症和双相抑郁症等精神疾病有关[6]。

唇缘结合试验。[2]
测定条件如下所述。使用不同的Tris-HCl缓冲液进行了一系列平衡饱和度研究。简而言之，将50 pl的['Humigand（1 nM，竞争研究中的最终浓度）、50 pl的药物或缓冲液以及400 pl的脑或CHO Kl细胞膜加入到适当的冰冷缓冲液中，使总体积为500 l_l。在25℃下孵育60分钟，然后通过Whatman GF/B玻璃纤维过滤器在Brandel MR48细胞采集器上用1 ml缓冲液洗涤四次（在0.5%PEI中预浸约一小时）来终止孵育。加入10 ml液体闪烁Ready Gel鸡尾酒并提取过夜后，用Beckman LS 6800液体计数过滤器上剩余的放射性。闪烁计数器（50%效率）。特异性结合定义为在1pM氟哌啶醇存在下的总结合减去结合，范围为90-95%。所有检测均一式三份。CHOKl细胞的粗膜每个测定管的蛋白质含量在40pg-60pg之间。蛋白质通过Bradford测定法使用酶标仪进行分析。

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饱和度研究。[2]
用九种浓度递增的[w]PD-128907（0.039-10.0 r&l）测定饱和结合曲线。如前所述，在25℃下用组织匀浆孵育60分钟。通过使用不同的缓冲液（TE=25 mM Tris-HCl，1 mM EDTA；TEM=25 mM Tris-HCl，1 mM乙二胺四乙酸，6 mM氯化镁，TEN=2.5 mM Tris-HHCl，1 mmol EDTA，12

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动力学实验。[2]
使用TEM缓冲液用['H]PD-128907（1.0 nM，终浓度）进行缔合和解离实验。在关联实验中，在1pM氟哌啶醇存在下定义特异性结合，并在不同时间过滤样品。在解离研究中，还通过添加过量的PD-128907（最终浓度为20 pM）在不同时间（按照上述确定的平衡度）过滤样品。离解和缔合的速率常数之比（k-l/k+l）用于计算r3H]PD 128907（n=3）的&。

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共代谢研究。[2]
在CHO-Kl-D中使用1 nM[SH]PD-128907测定各种药物的抑制常数（IS，），细胞膜和测定用TEM缓冲液进行。制备了八种不同浓度的每种配体，并进行了三次研究。研究了非水解GTP类似物Gpp（NH）p对DA抑制[“H]PD 128907与CHO-Kl-D膜结合的影响。

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(+)-PD 128907 盐酸盐是 D2/D3 多巴胺受体的选择性激动剂。其对人和大鼠 D3 受体的 Kis 值分别为 1.7、0.84 nM 和 179、770 nM。

组织培养。[2]
CHO细胞以及随后用人D、和D cDNA转染的CHO细胞在37℃的95%空气和5%CO的气氛下维持。CHO细胞在含有100 U/ml青霉素-链霉素和透析胎牛血清的F-12培养基中生长和传代。每2-3天更换一次培养基，在收获细胞前至少18小时更换一次。通过用含有0.05%EDTA的冷磷酸盐缓冲盐水（PBS）代替培养基，然后在1000 g下离心2分钟，收获融合的培养物。将获得的颗粒悬浮在适当体积的冰冷缓冲液（25 mM Tris-HCl，1 mM EDTA，pH 7.4，TE缓冲液）中，并在4℃下在20000 g下离心15分钟。将得到的最终颗粒悬浮在TE缓冲液中，在6℃下用Polytron均质化5秒，用于放射性配体结合测定，或储存在-80*C下。将用于测定的CHO Kl细胞膜在6℃用Polytron。

Extracellular single-unit recordings. [3]
All methods for extracellular single-cell recordings were similar to those previously reported (White et al., 1995), although modified somewhat for the mouse (Xu et al., 1994). Briefly, mice were anesthetized with chloral hydrate (400 mg/kg, i.p.) and mounted in a standard stereotaxic apparatus with a specialized adapter for the mouse. Body temperature was maintained at 36–37.5°C with a thermostatically controlled heating pad. A 28 gauge (3/8 inch) hypodermic needle was placed in a lateral tail vein through which additional anesthetic (as required) and drugs of study were administered. A burr hole was drilled in the skull, and the dura was retracted from the area overlying the VTA and SN, 0.4–1.3 mm anterior to lambda and 0.2–1.0 mm lateral to the midline. Recording electrodes were made by pulling glass tubing [outer diameter (o.d.), 2.0 mm], which was prefilled with fiberglass, and by breaking the tip back to a diameter of 1–2 μm. Electrodes were filled with 2 m NaCl saturated with 1% (w/v) fast green dye and typically exhibitedin vitro impedances of 1–3 MΩ (at 135 Hz). Electrode potentials were passed through a high impedance amplifier/filter and displayed on an oscilloscope. Individual action potentials were discriminated electronically and monitored with an audio amplifier. Integrated rate histograms, generated by the output of the window discriminator, were plotted by a polygraph recorder, whereas digitized counts of cellular activity were obtained for off-line analysis. Electrodes were lowered to a point 0.5 mm above the VTA and SN and then slowly advanced with a hydraulic microdrive through the DA cell regions (3.2–5.0 mm ventral to the cortical surface). DA cells were identified by standard physiological criteria (Bunney et al., 1973; Wang, 1981;Sanghera et al., 1984) and were recorded for 3–6 min to establish a baseline firing rate. To determine the sensitivity of impulse-modulating somatodendritic autoreceptors, we administered PD-128907 to each mouse through the tail vein, using a cumulative dose regimen in which each dose doubled the previous dose, at 60–90 sec intervals. After agonist-induced inhibition, the D2-class receptor antagonist eticlopride was administered (0.1–0.2 mg/kg) to reverse the effect and confirm receptor mediation. At the end of each experiment, the cell location was marked by ejecting fast green dye, and the spot was verified by routine histological assessment (described below).

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γ-Butyrolactone experiments. [3]
The l-aromatic amino acid decarboxylase inhibitor NSD 1015 was administered 30 min before death (100 mg/kg, i.p.). γ-Butyrolactone (GBL) was administered (750 mg/kg, i.p.) 5 min before NSD 1015 to eliminate impulse flow in DA neurons (Walters and Roth, 1976). PD-128907 was injected 5 min before GBL. Mice were killed by decapitation, and the brains were quickly removed. Dorsal and ventral striatum were dissected on a chilled glass plate with the aid of a mouse brain matrix designed to allow coronal sections to be cut rapidly and reproducibly (Activational Systems, Warren, MI). Two slices (2 mm each) were taken, beginning at the rostral boundary of the olfactory tubercle. The most anterior slice was the source of ventral striatum, whereas both slices were used to obtain dorsal striatum. The ventral striatum was dissected with angular cuts originating at the lateral olfactory tracts and ending at the midline (average weight, 18.5 mg). The remainder of the striatal region from that slice as well as the similar region from the more caudal slice was considered the dorsal striatum (average weight, 35.8 mg). Tissues were kept at −80°C. To measure tissue catechols, we weighed frozen tissues and then sonically disrupted them in a homogenization solution consisting of 100 mmHClO4, 5 mmNa2S2O5, and α-methyl dopa, an internal standard. After centrifugation (25,000 ×g for 10 min), aliquots of the supernatant were processed by alumina extraction as described previously (Galloway et al., 1986). The 3,4-dihydroxyphenylalanine (DOPA) content of samples was determined using an HPLC system consisting of a Bioanalytical Systems (BAS) Phase II ODS 3 μm column (100 × 3.2 mm), a BAS LC4C electrochemical detector, and a Scientific Systems model 222C HPLC pump. The mobile phase consisted of 0.1 mNaH2PO4, 1 mm EDTA, 0.2 mm 1-octane-sulfonic acid, and 3% methanol, adjusted to pH 2.7 with phosphoric acid. DOPA content was quantified based on both internal and external standards.

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In vivo microdialysis experiments. [3]
Mice used for dialysis experiments weighed 28–35 gm. Concentric microdialysis probes were constructed as described previously, with fused-silica inlet and outlet lines (Wolf et al., 1994). Dialysis membrane (molecular weight cutoff, 6000; o.d., 250 μm) was obtained from Spectrum (Los Angeles, CA). Data were not corrected for in vitro probe recovery because probes may suffer differential alterations during insertion. Consistent with this assumption, data sets corrected for recovery often exhibit greater variability than do those that are uncorrected (Xue et al., 1996). Probes were stereotaxically implanted under sodium Brevital (8 mg/kg, i.p.). Stereotaxic coordinates were, relative to bregma, anterior, 1.5 mm; lateral, 1.5 mm; and ventral, 2.7–4.7 mm. Ventral coordinates indicate exposed regions of dialysis membrane (2 mm). After surgery, mice were placed in Plexiglas cages (23 × 46 mm) and allowed to recover overnight. Food and water were available ad libitum. Dialysis cages were equipped with balance arms (Instech, Plymouth Meeting, PA), and homemade liquid swivels and tethers were constructed from plastic syringes and tubing. These were used because commercially available swivels were too heavy for use with mice. Probes were perfused overnight at 0.3 μl/min with artificial CSF (aCSF) consisting of (in mm): 2.7 KCl, 140 NaCl, 1.2 CaCl2, 1 MgCl2, 0.3 NaH2PO4, and 1.7 Na2HPO4, pH 7.4. The next morning, the perfusion rate was increased to 2 μl/min for 2–3 hr before the experiment was begun. Experiments consisted of 1 hr of perfusion with control aCSF to determine basal DA efflux, 1 hr of perfusion with aCSF containing PD-128907, and a 1 hr recovery period during which control aCSF was perfused. Thus, administration of PD-128907 occurred ∼20 hr after probe implantation. Fractions were collected every 20 min. After each experiment, mice were anesthetized and perfused intracardially with normal saline followed by 10% formalin. Probe placement was examined in sections stained with cresyl violet. Only data from mice with verified probe placements were included in the analysis. Dialysates were analyzed for DA content using the HPLC system described for GBL experiments. Chromatographic conditions were optimized for early elution of DA to obtain maximum sensitivity. The mobile phase consisted of 0.1 m NaH2PO4, 0.5 mm EDTA, 2 mm 1-octane-sulfonic acid, and 16% methanol, adjusted to pH 4.9. Peaks were recorded using a dual-channel chart recorder and were quantified by comparison with the peak heights of external standards run with every experiment.

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Dissolved in water; 3 mg/kg; i.p. injection

Mouse

[1]. Neuroreport. 1995 Jan 26;6(2):329-32.

[2]. Life Sci. 1995;57(15):1401-10.

[3]. J Neurosci. 1998 Mar 15;18(6):2231-8.

[4]. J Pharmacol Exp Ther. 1995 Dec;275(3):1355-66.

[5]. J Pharmacol Exp Ther. 2004 Mar;308(3):957-64.

[6]. J Pharmacol Exp Ther. 2008 Sep;326(3):930-8.

As described above, studies using [SH]PD-128907 on CHO-Kl-D₁ cell membranes in the presence of Na⁺ (120 mM) showed a slight decrease in Kₐ values, but this was not statistically significant. These results may indicate that Na⁺ does not induce conformational changes in the D₁ receptor as previously proposed. In addition to Na⁺, guanylic acid has also been shown to reduce the binding of agonists to G protein-coupled receptors. Adding 100 pM of the non-hydrolyzable GTP analog Gpp(NH)p to the DA substitution curve did not alter the DA competition curve, indicating a lack of significant functional coupling between the human D₁ receptor and the G protein-regulated signal transduction system in CHO-Kl cells (Table II). These findings are consistent with previous studies published in CHO and MN9D cells, indicating that the coupling between the D receptor and G protein is absent or only weak (see references 2.5 and 26, where the results are contradictory). However, another study showed that recombinant D receptors expressed heterogeneously in CHO cells can functionally interact with endogenous G proteins. The reasons for these differences are unclear, but may be related to the presence of different signaling pathways in certain cell clones where G protein regulation has been described. Consistent with our current data, guanylic acid was observed to have weak or no regulatory effect on DA binding on the native D receptor using [SH]7-OH-DPAT and [''1]7-OH-PIPAT, respectively. The lack of suitable G protein isoforms in various cell lines and/or D receptors may be a possible explanation for this phenomenon if the native coupling mechanism/channel is absent or not coupled to G proteins. [3H]PD-128907 appears to be a highly selective D radioligand with high specific activity, good specific yield, and low nonspecific binding. [3H]PD-128907 is suitable for studies such as autoradiography to assess the presence and distribution of D receptors in the brain and may characterize the function of this receptor subtype (if any). [2] Our microdialysis study showed a significant increase in basal dopamine (DA) efflux in the ventral striatum of D3 receptor mutant mice compared to wild-type littermates. Although “netless flux” dialysis studies are usually required to quantify differences in basal neurotransmitter efflux in vivo (see Justice, 1993 for a review), the difference between D3 receptor mutant mice and wild-type mice was very significant, with all but one mutant mouse showing higher basal DA efflux than any wild-type mouse. If the D3 autoreceptors at nerve endings typically exert a sustained inhibitory effect on dopamine release, then basal dopamine efflux might be increased. However, the results of PD 128907 do not conform to this simple interpretation, as this assumed D3 receptor selective agonist has the same absolute inhibitory effect on dopamine release in both D3 receptor mutant and wild-type mice. Therefore, D3 receptor mutations did not lead to a weakening of dopamine autoreceptor regulation. Although the percentage reduction in DA release induced by PD-128907 in mutant mice was small, this effect could be attributed to its higher basal DA levels, which are known to reduce the ability of DA agonists to inhibit DA release (Cubeddu and Hoffman, 1982; Dwoskin and Zahniser, 1986; see review in Wolf and Roth, 1987). Another explanation is that DA release is normally dual-regulated by a negative feedback pathway mediated by D2 release-regulating autoreceptors and postsynaptic D3 (and other D2 class) receptors. Loss of D3 receptor-mediated inhibitory feedback could explain the increased basal DA efflux, while PD-128907 activation of D2 release-regulating autoreceptors could explain its normal inhibitory effect on DA release. This model is consistent with findings on D3 mRNA, suggesting that D3 receptors are primarily distributed within target neurons of the ascending dopamine system. In the ventral striatal terminal regions (nucleus accumbens, olfactory tubercle, and Kaleha Island) where D3 receptor expression is highest, the D3 receptor mRNA level closely matches the D3 receptor binding site (Diaz et al., 1995), suggesting that most D3 receptors are located in the dendrites, cell bodies, or local terminals of intrinsic neurons. If postsynaptic D3 receptors are coupled to feedback pathways that normally inhibit dopamine release, the loss of such feedback may lead to an increase in basal dopamine efflux, but the effects mediated by D2 autoreceptors remain unchanged. [3]

C14H20CLNO3

285.77

285.113

C, 58.84; H, 7.05; Cl, 12.41; N, 4.90; O, 16.80

112960-16-4

112960-16-4; 23594-64-9; 300576-59-4 (HCl)

11957668

White to light yellow solid powder

145-153°C

2.676

41.93

2

4

2

19

286

2

Cl.CCCN1CCO[C@@H]2C3C=C(O)C=CC=3OC[C@@H]12

DCFXOTRONMKUJB-QMDUSEKHSA-N

InChI=1S/C14H19NO3.ClH/c1-2-5-15-6-7-17-14-11-8-10(16)3-4-13(11)18-9-12(14)15;/h3-4,8,12,14,16H,2,5-7,9H2,1H3;1H/t12-,14-;/m1./s1

(4aR,10bR)-4-propyl-3,4a,5,10b-tetrahydro-2H-chromeno[4,3-b][1,4]oxazin-9-ol;hydrochloride

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

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

注意: 如下所列的是一些常用的体内动物实验溶解配方，主要用于溶解难溶或不溶于水的产品（水溶度<1 mg/mL）。 建议您先取少量样品进行尝试，如该配方可行，再根据实验需求增加样品量。

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注射用配方1: DMSO : Tween 80： Saline = 10 : 5 : 85 (如： 100 μL DMSO → 50 μL Tween 80 → 850 μL Saline)
*生理盐水/Saline的制备：将0.9g氯化钠/NaCl溶解在100 mL ddH ₂ O中，得到澄清溶液。
注射用配方 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL DMSO → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)
注射用配方 3: DMSO : Corn oil = 10 : 90 (如： 100 μL DMSO → 900 μL Corn oil)
示例: 以注射用配方 3 (DMSO : Corn oil = 10 : 90) 为例说明, 如果要配制 1 mL 2.5 mg/mL的工作液, 您可以取 100 μL 25 mg/mL 澄清的 DMSO 储备液，加到 900 μL Corn oil/玉米油中, 混合均匀。

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注射用配方 4: DMSO : 20% SBE-β-CD in Saline = 10 : 90 [如：100 μL DMSO → 900 μL (20% SBE-β-CD in Saline)]
*20% SBE-β-CD in Saline的制备（4°C，储存1周）：将2g SBE-β-CD (磺丁基-β-环糊精) 溶解于10mL生理盐水中，得到澄清溶液。
注射用配方 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (如： 500 μL 2-Hydroxypropyl-β-cyclodextrin (羟丙基环胡精)→ 500 μL Saline)
注射用配方 6: DMSO : PEG300 : Castor oil : Saline = 5 : 10 : 20 : 65 (如： 50 μL DMSO → 100 μL PEG300 → 200 μL Castor oil → 650 μL Saline)
注射用配方 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (如： 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
注射用配方 8: 溶解于Cremophor/Ethanol (50 : 50), 然后用生理盐水稀释。
注射用配方 9: EtOH : Corn oil = 10 : 90 (如： 100 μL EtOH → 900 μL Corn oil)
注射用配方 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL EtOH → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)

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口服配方 1: 悬浮于0.5% CMC Na (羧甲基纤维素钠)
口服配方 2: 悬浮于0.5% Carboxymethyl cellulose (羧甲基纤维素)
示例: 以口服配方 1 (悬浮于 0.5% CMC Na)为例说明, 如果要配制 100 mL 2.5 mg/mL 的工作液, 您可以先取0.5g CMC Na并将其溶解于100mL ddH2O中，得到0.5%CMC-Na澄清溶液；然后将250 mg待测化合物加到100 mL前述 0.5%CMC Na溶液中，得到悬浮液。

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口服配方 3: 溶解于 PEG400 (聚乙二醇400)
口服配方 4: 悬浮于0.2% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 5: 溶解于0.25% Tween 80 and 0.5% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 6: 做成粉末与食物混合

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注意: 以上为较为常见方法，仅供参考， InvivoChem并未独立验证这些配方的准确性。具体溶剂的选择首先应参照文献已报道溶解方法、配方或剂型，对于某些尚未有文献报道溶解方法的化合物，需通过前期实验来确定（建议先取少量样品进行尝试），包括产品的溶解情况、梯度设置、动物的耐受性等。

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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。