U-62066 (mesylate)
(Synonyms: U-62066 mesylate) 目录号 : GC45106
An Analytical Reference Standard
Cas No.:87173-97-5
Sample solution is provided at 25 µL, 10mM.
;)
,-1-7$$$37316672.jpg');)
;)
;)
$$$36806353.jpg');)
;33(7)%EF%BC%9A546-561$$$37156877.jpg');)
;)
;)
;)
%201124-1138.$$$35908550.jpg');)
%20766-780.$$$37100057.jpg');)
%20418-432.$$$36893736.jpg');)
%EF%BC%9A-240-255.$$$35108512.jpg');)
533-545$$$36543525.jpg');)
%201-13.$$$36600053.jpg');)
;)
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
U-62066 (mesylate) is an analytical reference standard categorized as an opioid. This product is intended for research and forensic applications.
| Cas No. | 87173-97-5 | SDF | |
| 别名 | U-62066 mesylate | ||
| Canonical SMILES | ClC1=C(Cl)C=CC(CC(N(C)[C@H]2CC[C@]3(OCCC3)C[C@@H]2N4CCCC4)=O)=C1.CS(O)(=O)=O | ||
| 分子式 | C22H30Cl2N2O2•CH3SO3H | 分子量 | 521.5 |
| 溶解度 | DMSO: slightly soluble,PBS (pH 7.2): 0.5 mg/ml | 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。 |
||
| 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 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 1.9175 mL | 9.5877 mL | 19.1755 mL |
| 5 mM | 0.3835 mL | 1.9175 mL | 3.8351 mL |
| 10 mM | 0.1918 mL | 0.9588 mL | 1.9175 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。
Gender differences in kappa-opioid modulation of cocaine-induced behavior and NMDA-evoked dopamine release
Brain Res 1998 Aug 10;801(1-2):67-71.PMID:9729284DOI:10.1016/s0006-8993(98)00546-0.
It has been reported that kappa-opioids produce greater analgesia in women than in men. Sex differences are also apparent in drug-induced behaviors. Repeated administration of cocaine (25 mg/kg) produced a greater locomotor and sensitization response in C57BL/6By female mice. It was examined whether the increased sensitization in females to repeated cocaine administration was related to differences in kappa-opioid responses. The effects of the kappa agonist U62066 (spiradoline mesylate) on cocaine-induced locomotor stimulation in vivo and NMDA-mediated dopamine release in vitro were measured. In male, but not female mice, U62066 (1 mg/kg) given 30 min before cocaine potentiated the locomotor stimulation of an acute cocaine administration. U-62066 did not affect the development of locomotor sensitization with repeated cocaine administration (25 mg/kg s.c., once daily for 3 days), and a further enhanced response was not seen on days 2 and 3. It was then examined whether dopamine release, measured in vitro, plays a role in sex dependent differences in kappa-opioid- or NMDA-modulated dopaminergic function. In tissue perfusion studies, the in vitro NMDA (25 microM)-evoked release of labelled dopamine from striatum was lower in females (fractional release = 5.4 +/- 0.4 and 4.0 +/- 0.4 in male and female mouse striatum). U62066 (1 microM) and ibogaine (1 microM), an indole alkaloid claimed to be useful in the treatment of drug addiction that acts in part at the kappa-opioid receptor, both reduced the NMDA (25 microM)-evoked release of dopamine. Inhibition of the release was significantly greater in tissue from male mice. Prior in vivo cocaine administration did not alter the NMDA-evoked dopamine release. Our studies indicate that kappa-opioid and NMDA receptor activity show differences between female and male mice that may account for differences in cocaine-induced behaviors, but do not exclude the role of other hetereoceptors modulating dopamine release.
Emerging treatment strategies in Tourette syndrome: what's in the pipeline?
Int Rev Neurobiol 2013;112:445-80.PMID:24295630DOI:10.1016/B978-0-12-411546-0.00015-9.
Tourette syndrome (TS) is a neurodevelopmental disorder characterized by multiple motor/phonic tics and a wide spectrum of behavioral problems (e.g., complex tic-like symptoms, attention deficit hyperactivity disorder, and obsessive-compulsive disorder). TS can be a challenging condition even for the specialists, because of the complexity of the clinical picture and the potential adverse effects of the most commonly prescribed medications. Expert opinions and consensus guidelines on the assessment and treatment of tic disorders have recently been published in Europe and Canada. All pharmacological treatment options are mere symptomatic treatments that alleviate, but do not cure, the tics. We still lack evidence of their effects on the natural long-term course and on the prognosis of TS and how these treatments may influence the natural course of brain development. The most commonly prescribed drugs are dopamine antagonists, such as typical (e.g., haloperidol, pimozide) and atypical neuroleptics (e.g., risperidone, aripiprazole), and α-2-adrenoreceptor agonists (e.g., clonidine). However, several studies have investigated the efficacy and tolerability of alternative pharmacological agents that may be efficacious, including the newest atypical antipsychotic agents (e.g., paliperidone, sertindole), tetrabenazine, drugs that modulate acetylcholine (e.g., nicotine) and GABA (e.g., baclofen, levetiracetam), tetrahydrocannabinol, botulinum toxin injections, anticonvulsant drugs (e.g., topiramate, carbamazepine), naloxone, lithium, norepinephrine, steroid 5α reductase, and other neuroactive agents (buspirone, metoclopramide, phytostigmine, and spiradoline mesylate). As regards nonpharmacological interventions, some of the more recent treatments that have been studied include electroconvulsive therapy and repetitive transcranial magnetic stimulation. This review focuses primarily on the efficacy and safety of these emerging treatment strategies in TS.
Roles of different subtypes of opioid receptors in mediating the ventrolateral orbital cortex opioid-induced inhibition of mirror-neuropathic pain in the rat
Neuroscience 2007 Feb 23;144(4):1486-94.PMID:17184926DOI:10.1016/j.neuroscience.2006.11.009.
Previous studies have demonstrated that opioid receptors in the prefrontal ventrolateral orbital cortex (VLO) are involved in anti-nociception. The aim of this current study was to examine whether opioid receptors in the VLO have effects on the hypersensitivity induced by contralateral L5 and L6 spinal nerve ligation (SNL), termed as mirror neuropathic pain (MNP) in the male rat. Morphine (1.0, 2.5, 5.0 microg) microinjected into the VLO contralateral to the SNL depressed the mechanical paw withdrawal assessed by von Frey filaments and the cold plate (4 degrees C)-induced paw lifting in a dose-dependent manner on the side without SNL. These effects were antagonized by microinjection of the non-selective opioid receptor antagonist naloxone (1.0 mug) into the same VLO site. Microinjection of endomorphin-1 (5.0 microg), a highly selective mu-opioid receptor agonist, and [d-Ala(2), d-Leu(5)]-enkephalin (DADLE, 10 microg), a delta-/mu-receptor agonist, also depressed the MNP. The effects of both drugs were blocked by selective mu-receptor antagonist beta-funaltrexamine (beta-FNA, 3.75 microg), but the effect of the DADLE was not influenced by the selective delta-receptor antagonist naltrindole (5.0 microg). Microinjection of the kappa-opioid receptor agonist spiradoline mesylate salt (U-62066) (100 microg) had no effect on the MNP. These results suggest that the VLO is involved in opioid-induced inhibition of the MNP and the effect is mediated by mu- (but not delta- and kappa-) opioid receptors.
A review of the properties of spiradoline: a potent and selective kappa-opioid receptor agonist
CNS Drug Rev 2003 Summer;9(2):187-98.PMID:12847558DOI:10.1111/j.1527-3458.2003.tb00248.x.
The selective kappa-opioid receptor agonist spiradoline mesylate (U62,066E), an arylacetamide, was synthesized with the intention of creating an analgesic that, while still retaining its analgesic properties, would be devoid of the, mainly mu receptor mediated, side effects such as physical dependence and respiratory depression associated with morphine. Spiradoline is highly selective for the kappa receptor with K(i) of 8.6 nM in guinea pig. Examination of the enantiomers of spiradoline, showed the (-)enantiomer to be responsible for the kappa agonist properties. Spiradoline easily penetrates the blood brain barrier, and does not seem to have any significant active metabolites. In preclinical studies, spiradoline has a short duration of action with a peak at around 30 min after administration. The analgesic properties of spiradoline are well documented in mice and rats. Antitussive properties have also been reported in rats. Furthermore, spiradoline was reported to display effects suggestive of neuroprotective properties in animal models of ischemia. In humans, spiradoline is a potent diuretic. It also produces significant sedation presumably due to its antihistamine properties. Preclinical studies have shown that spiradoline reduces blood pressure and heart rate, and has possible antiarrhythmic properties. Clinical studies did not confirm these findings. kappa Receptors inhibit dopaminergic neurotransmission. Spiradoline, given systematically to rats, produces a significant and long lasting decrease in dopamine release, and in locomotor activity. It has also antipsychotic-like effect in animal behavioral tests. At low doses spiradoline was reported to decrease tics in patients with Tourette's syndrome. Although spiradoline had promising effects in animal tests of analgesia, and a reasonably good safety profile in preliminary studies, it did not replace morphine as an analgesic. The available clinical data suggest that spiradoline produces disturbing adverse effects such as diuresis, sedation, and dysphoria at doses lower than those needed for analgesic effects. Thus, future development of spiradoline-like analgesic compounds should preferably focus on reduction of unwanted effects on the central nervous system. Spiradoline, which currently is commercially available for preclinical research, might prove useful in some psychiatric conditions and possibly as a neuroprotective agent.
Analgesic activity of spiradoline mesylate (U-62,066E), a kappa opioid agonist in mice
Life Sci 1989;45(13):1191-8.PMID:2796604DOI:10.1016/0024-3205(89)90508-0.
The present study was undertaken to evaluate the analgesic potency of spiradoline mesylate, a k(kappa) opioid agonist, in comparison with that of morphine, by hot plate, tail-pinch and acetic acid-induced writhing assay. The ED50 values of spiradoline in hot plate, tail-pinch and acetic acid-induced writhing assay were 0.46, 0.26 and 0.20 mg/kg, respectively. The analgesic potency of spiradoline was 1.5-7.0 times higher than that of morphine. Repeated treatment with spiradoline as well as morphine developed tolerance to the analgesic effect in hot plate assay. In mice developed tolerance to one analgesic, response to the other analgesic did not alter compared to saline-treated mice. Single administration of spiradoline (1.5 and 3 mg/kg, s.c.) did not inhibit morphine-induced analgesia. These results suggest that spiradoline has more potent analgesic activity than morphine, presumably mediated through stimulation of receptors different from morphine.