Naxagolide
(Synonyms: (+)-PHNO; Dopazinol) 目录号 : GC67705Naxagolide ((+)-PHNO; Dopazinol) 是一种有效的多巴胺 D2 (dopamine D2) (Dopamine Receptor) 激动剂。Naxagolide 具有用于帕金森病 (PD) 研究的潜力。
Cas No.:88058-88-2
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Naxagolide ((+)-PHNO; Dopazinol) is a potent dopamine D2 (Dopamine Receptor) agonist. Naxagolide has the potential for the research of parkinson's disease (PD)[1][2].
在体外，Naxagolide ((+)-PHNO) 抑制大鼠纹状体膜上的 [3H]apomorphine (IC50 = 23 nM) 或 [3 H]spiperone (IC50 = 55 nM)[1]。
在小鼠中，Naxagolide ((+)-PHNO) 在单侧尾部切除的动物中产生体温过低 (13 μg/kg i.p.) 和姿势不对称 (4 μg/kg i.p.)[1]。
在大鼠中，Naxagolide ((+)-PHNO) 在 6-羟基多巴胺损伤的动物中产生刻板印象（10 μg/kg i.p.）和对侧转向（5 μg/kg i.p.），持续 1 至 3 小时[1] 。
[1]. G E Martin, et al. Pharmacologic profile of a novel potent direct-acting dopamine agonist, (+)-4-propyl-9-hydroxynaphthoxazine [(+)-PHNO]. J Pharmacol Exp Ther. 1984 Sep;230(3):569-76.
[2]. E F Domino, et al. Relative potency and efficacy of some dopamine agonists with varying selectivities for D1 and D2 receptors in MPTP-induced hemiparkinsonian monkeys. J Pharmacol Exp Ther. 1993 Jun;265(3):1387-91.
| Cas No. | 88058-88-2 | SDF | Download SDF |
| 别名 | (+)-PHNO; Dopazinol | ||
| 分子式 | C15H21NO2 | 分子量 | 247.33 |
| 溶解度 | DMSO : 200 mg/mL (808.64 mM; Need ultrasonic) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 4.0432 mL | 20.2159 mL | 40.4318 mL |
| 5 mM | 0.8086 mL | 4.0432 mL | 8.0864 mL |
| 10 mM | 0.4043 mL | 2.0216 mL | 4.0432 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Differential effects of direct and indirect dopamine agonists on eye blink rate in cynomolgus monkeys
J Pharmacol Exp Ther 1996 Dec;279(3):1211-9.PMID:8968343doi
Spontaneous eye blink rate was assessed in cynomolgus monkeys treated intramuscularly with the high-efficacy dopamine (DA) agonists, (-)-apomorphine, Naxagolide, PD 128,907, 2-(N-phenylethyl-N-propyl)amino-5-hydroxytetralin (+/-)-PPHT, quinpirole, SKF 81297 and SKF 82958; the low-efficacy DA agonists, (-)-3-PPP, roxindole, SDZ 208-912, SKF 75670 and terguride; and the indirect DA agonists, d-amphetamine, cocaine, GBR 12935 and methylphenidate. All of the direct DA agonists, with the exception of the partial agonists SDZ 208-912 and terguride, produced significant, dose-related elevations in blink rate. In contrast, none of the indirect agonists increased blink rates when administered over a relatively wide, behaviorally active dose range. These differences suggest either that indirect agonists do not interact with mechanisms involved in eye blinking, or that they have other effects which prevent blink-rate increases. The latter does not appear to be the case because cocaine failed to alter the blink rate-increasing effects of the D1 agonist, SKF 81297, which suggests that indirect agonists do not mask their own ability to induce blinking. Overall, the results further characterize the involvement of DA receptors in the mediation of spontaneous eye blinks, reveal differential effects of direct and indirect agonists and suggest new directions for research into the neuroanatomical basis of DA-mediated spontaneous eye blinks.
Comparison between the pharmacology of dopamine receptors mediating the inhibition of cell firing in rat brain slices through the substantia nigra pars compacta and ventral tegmental area
Br J Pharmacol 1994 Jul;112(3):873-80.PMID:7921615DOI:10.1111/j.1476-5381.1994.tb13161.x.
1. Electrophysiological recordings were made from presumed dopaminergic neurons in the substantia nigra pars compacta and ventral tegmental area of rat brain slices. The ability of selective dopamine receptor agonists to hyperpolarize neurones and inhibit cell firing, as well as the ability of dopamine receptor antagonists to block responses to quinpirole were compared. 2. Six dopamine receptor agonists were examined for their ability to hyperpolarize neurones within the substantia nigra pars compacta. Of these, the most potent ligand tested was Naxagolide with an EC50 value of 20 nM and estimated maximum of 10 mV. The rank order of agonist potency was Naxagolide > quinpirole > apomorphine > dopamine. 3. Quinpirole was more potent at inhibiting cell firing in the substantia nigra pars compacta (pIC50 = 7.65 +/ 0.06, n = 35) than in the ventral tegmental area (pIC50 = 7.24 +/- 0.06, n = 32; P < 0.01, Student's t test). 7-Hydroxy-N,N-di-n-propyl-2-aminotetralin (7-OH-DPAT), a putative D3 selective agonist, had a comparable potency to quinpirole in both the ventral tegmental area (pIC50 = 7.39 +/- 0.26, n = 4), and substantia nigra pars compacta (pIC50 = 7.71 +/- 0.20; n = 4). 4. The inhibition of cell firing by quinpirole was antagonized by haloperidol, S(-)-sulpiride, clozapine, and ritanserin. S(-)-sulpiride and haloperidol had the highest estimated affinities in the substantia nigra, with pA2 values of 8.97 (slope = 0.85) and 8.20 (slope = 2.09) respectively. The pA2 values for S(-)-sulpiride and haloperidol in the ventral tegmental area were 8.07 (slope = 0.87) and 8.11 (slope = 1.48)respectively. Clozapine had a lower functional affinity than S(-)-sulpiride and haloperidol in both the substantia nigra (pA2 = 6.47, slope = 1.19) and ventral tegmental area (pA2 = 6.53, slope 0.87). Ritanserin,a 5-HT2 receptor antagonist that also binds to D2.u. dopamine receptors, caused a slight but significant shift in the concentration-effect curve to quinpirole with an estimated pKA of 6.97 +/- 0.13(n =4) in the substantia nigra and pKA of 7.12 +/- 0.22 (n =4) in the ventral tegmental area.5. Comparison of these data with the binding affinity for cloned dopamine receptors demonstrates that the responses to quinpirole on dopaminergic neurones in both the A9 (substantia nigra) and A10(ventral tegmental area) brain areas are consistent with the activation of predominantly D2, and not D3 or D4 dopamine receptors. Furthermore, the similarity in functional affinity of antagonists for these receptors suggest that the mesolimbic selectivity of atypical neuroleptics, like clozapine, may be a consequence of their actions on other receptors or their effects elsewhere in the brain.
Relative potency and efficacy of some dopamine agonists with varying selectivities for D1 and D2 receptors in MPTP-induced hemiparkinsonian monkeys
J Pharmacol Exp Ther 1993 Jun;265(3):1387-91.PMID:8099621doi
A series of dopamine agonists were studied on contraversive circling behavior in seven 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced hemiparkinsonian monkeys. The compounds selected included [1R,3S]3-(1' adamantyl)-1-aminomethyl-3,4-dihydro-5-6- dihydroxy-1H-2-benzopyran hydrochloride (A-77636), L-3,4-dihydroxyphenylalanine methyl ester hydrochloride ester (L-dopa-methyl ester), (-)-2-[N-propyl-N-(2-thienyl) ethyl-amino-5-hydroxy-tetralin]hydrochloride (N-0923), pergolide, (+)-(4aR)-trans-3,4,4a,5,6,10b-hexahydro-4-propyl-2H-n aphth[1,2-b]-1,2-oxazin-9-ol, Naxagolide (PHNO), (+/-)6-chloro-7, 8-dihydroxy-2,3,4,5-tetrahydro-1-phenyl-1H-3-benzazepine hydrobromide, (+-) chloro-PB hydrobromide (SKF-81297) and (+-) 6-chloro-7,8-dihydroxy-3-allyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benza zep ine hydrobromide, (+-) chloro-APB hydrobromide (SKF-82958). The dose-effect relationship of each of these compounds was determined by measuring contraversive turns/120 min after an i.m. injection. There were marked differences in the potency and efficacy of the various compounds studied. The most potent compounds were the selective D2 agonists PHNO and N-0923. L-dopa methyl ester was equally effective, but much less potent. The D1 agonist A-77636 was equally effective. The D1 agonist SKF-82958 was also effective, but less potent. In the doses studied, the D1 agonist SKF-81297 was ineffective. With the exception of L-dopa methyl ester, the greater the D1/D2 affinity ratio, the greater the 50% of maximal dose to induce contraversive circling (r = 0.974, P < .05).