Naloxone methiodide
目录号 : GC63686
Naloxone methiodide 是一种外周限制性、非选择性和竞争性阿片受体 (opioid receptor) 拮抗剂。Naloxone methiodide 不能穿透血脑屏障。
Cas No.:93302-47-7
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: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Naloxone methiodide is a peripherally restricted, nonselective, and competitive opioid receptor antagonist. Naloxone methiodide does not penetrate the blood-brain barrier[1][2].
Naloxone‐methiodide (10 mg/mL; 200 μL; i.p.), induces abdominal hypersensitivity in IL-10-/- mice with colitis[2].
[1]. Basso L, et al. TRPV1 promotes opioid analgesia during inflammation. Sci Signal. 2019;12(575):eaav0711. Published 2019 Apr 2. [2]. Basso L, et al. Endogenous control of inflammatory visceral pain by T cell-derived opioids in IL-10-deficient mice. Neurogastroenterol Motil. 2020;32(2):e13743.
| Cas No. | 93302-47-7 | SDF | |
| 分子式 | C20H24INO4 | 分子量 | 469.31 |
| 溶解度 | DMSO : 250 mg/mL (532.70 mM; Need ultrasonic) | 储存条件 | 4°C, away from moisture |
| 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 | 2.1308 mL | 10.6539 mL | 21.3079 mL |
| 5 mM | 0.4262 mL | 2.1308 mL | 4.2616 mL |
| 10 mM | 0.2131 mL | 1.0654 mL | 2.1308 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。
Central opioid receptors mediate morphine-induced itch and chronic itch via disinhibition
Brain 2021 Mar 3;144(2):665-681.PMID:33367648DOI:10.1093/brain/awaa430.
Opioids such as morphine are mainstay treatments for clinical pain conditions. Itch is a common side effect of opioids, particularly as a result of epidural or intrathecal administration. Recent progress has advanced our understanding of itch circuits in the spinal cord. However, the mechanisms underlying opioid-induced itch are not fully understood, although an interaction between µ-opioid receptor (MOR) and gastrin-releasing peptide receptor (GRPR) in spinal GRPR-expressing neurons has been implicated. In this study we investigated the cellular mechanisms of intrathecal opioid-induced itch by conditional deletion of MOR-encoding Oprm1 in distinct populations of interneurons and sensory neurons. We found that intrathecal injection of the MOR agonists morphine or DAMGO elicited dose-dependent scratching as well as licking and biting, but this pruritus was totally abolished in mice with a specific Oprm1 deletion in Vgat+ neurons [Oprm1-Vgat (Slc32a1)]. Loss of MOR in somatostatin+ interneurons and TRPV1+ sensory neurons did not affect morphine-induced itch but impaired morphine-induced antinociception. In situ hybridization revealed Oprm1 expression in 30% of inhibitory and 20% of excitatory interneurons in the spinal dorsal horn. Whole-cell recordings from spinal cord slices showed that DAMGO induced outward currents in 9 of 19 Vgat+ interneurons examined. Morphine also inhibited action potentials in Vgat+ interneurons. Furthermore, morphine suppressed evoked inhibitory postsynaptic currents in postsynaptic Vgat- excitatory neurons, suggesting a mechanism of disinhibition by MOR agonists. Notably, morphine-elicited itch was suppressed by intrathecal administration of NPY and abolished by spinal ablation of GRPR+ neurons with intrathecal injection of bombesin-saporin, whereas intrathecal GRP-induced itch response remained intact in mice lacking Oprm1-Vgat. Intrathecal bombesin-saporin treatment reduced the number of GRPR+ neurons by 97% in the lumber spinal cord and 91% in the cervical spinal cord, without changing the number of Oprm1+ neurons. Additionally, chronic itch from DNFB-induced allergic contact dermatitis was decreased by Oprm1-Vgat deletion. Finally, naloxone, but not peripherally restricted Naloxone methiodide, inhibited chronic itch in the DNFB model and the CTCL model, indicating a contribution of central MOR signalling to chronic itch. Our findings demonstrate that intrathecal morphine elicits itch via acting on MOR on spinal inhibitory interneurons, leading to disinhibition of the spinal itch circuit. Our data also provide mechanistic insights into the current treatment of chronic itch with opioid receptor antagonist such as naloxone.
Naloxone methiodide reverses opioid-induced respiratory depression and analgesia without withdrawal
Eur J Pharmacol 2002 Jun 7;445(1-2):61-7.PMID:12065195DOI:10.1016/s0014-2999(02)01715-6.
Illicit opioid overdoses are a significant problem throughout the world, with most deaths being attributed to opioid-induced respiratory depression which may involve peripheral mechanisms. The current treatment for overdoses is naloxone hydrochloride, which is effective but induces significant withdrawal. We propose that selectively peripherally acting opioid receptor antagonists, such as Naloxone methiodide, could reverse respiratory depression without inducing predominantly centrally mediated withdrawal. Acute administration of morphine (300 mg/kg, i.p.) was found to significantly depress respiratory rate and induce analgesia (P<0.0001). Both naloxone hydrochloride and Naloxone methiodide were able to reverse these effects but Naloxone methiodide precipitated no significant withdrawal. Naloxone methiodide was also able to reverse opioid-induced respiratory depression (P<0.001) and antinociception (P<0.01) after chronic morphine administration (300 mg/kg/day for 5 days) without inducing significant withdrawal. Therefore, peripherally selective opioid receptor antagonists should be investigated as possible treatments for opioid-induced respiratory depression which do not induce adverse effects, such as withdrawal.
Naloxone and its quaternary derivative, Naloxone methiodide, have differing affinities for mu, delta, and kappa opioid receptors in mouse brain homogenates
Brain Res 2003 Feb 28;964(2):302-5.PMID:12576191DOI:10.1016/s0006-8993(02)04117-3.
Naloxone and Naloxone methiodide both act on opioid receptors but Naloxone methiodide has limited access to the brain. Naloxone methiodide has been shown to have a lower affinity for opioid receptors than naloxone in the rat and guinea pig but has not been tested in the mouse. We aimed to investigate this by using [3H]DAMGO, [3H]DPDPE and [3H]U-69,593 to compare the ability of naloxone and Naloxone methiodide to displace binding to mu, delta and kappa opioid receptors in mouse brain homogenates. Significant binding was observed for each receptor type and the binding affinity for naloxone versus Naloxone methiodide was found to be 15:1 for mu, 6:1 for kappa and 330:1 for delta receptors. Therefore, Naloxone methiodide does have a lower affinity for opioid receptors than naloxone in mouse brain tissue, which must be taken into consideration in experimental designs.
Effects of ICI204,448, Naloxone methiodide and levocetirizine on the scratching behavior induced by a κ-opioid antagonist, nor-BNI, in ICR mice
Immunopharmacol Immunotoxicol 2017 Oct;39(5):292-295.PMID:28745076DOI:10.1080/08923973.2017.1354879.
Objective: In this study, we aimed to study the effects of ICI204,448, Naloxone methiodide and levocetirizine on the scratching behavior induced by intradermal injection of a ?-opioid antagonist, nor-binaltorphimine (nor-BNI), into the rostral back of ICR mice were investigated. Materials and methods: Male ICR mice weighing 30?35 g were used. The number of scratching episodes were counted for 60 min after i.d. injection of nor-BNI. Results: nor-BNI dose dependently increased in the number of scratching episodes in ICR mice. nor-BNI-induced scratching behavior was inhibited by not only nalfurafine but also ICI204,448, a peripherally selective ?-opioid agonist. Naloxone and Naloxone methiodide, a peripherally restricted ?-opioid antagonist, also inhibited nor-BNI-induced scratching behavior. Scratching behavior induced by nor-BNI was inhibited by chlorpheniramine as well as levocetirizine, a third-generation H1 antagonist that does not cross into the CNS. Conclusion: These results suggest that scratching behavior induced by this ?-opioid antagonist, nor-BNI, is related to not only central but also peripheral opioid and H1 receptors.
Naloxone regulates the differentiation of neural stem cells via a receptor-independent pathway
FASEB J 2020 Apr;34(4):5917-5930.PMID:32154623DOI:10.1096/fj.201902873R.
The abilities of opioids to activate downstream signaling pathways normally depend on the binding between opioids and their receptors. However, opioids may also function in a receptor-independent manner, especially in neural stem cells (NSCs) in which the expression of opioid receptors and endogenous opioid agonists is low. When two opioids, morphine and naloxone, were used during the early stage of NSC differentiation, increased neurogenesis was observed. However, Naloxone methiodide, a membrane impenetrable analog of naloxone, did not affect the NSC differentiation. The abilities of morphine and naloxone to facilitate neurogenesis were also observed in opioid receptor-knockout NSCs. Therefore, morphine and naloxone promote neurogenesis in a receptor-independent manner at least during the early stage. In addition, the receptor-independent functions of opioids were not observed in methylcytosine dioxygenase ten-eleven translocation 1 (Tet1) knockout NSCs. When the expression of opioid receptors increased and the expression of Tet1 decreased during the late stage of NSC differentiation, morphine, but not naloxone, inhibited neurogenesis via traditional receptor-dependent and miR181a-Prox1-Notch-related pathway. In summary, the current results demonstrated the time-dependent effects of opioids during the differentiation of NSCs and provided additional insight on the complex functions of opioids.