Akuammine
(Synonyms: (-)-Akuammine, Vincamajoridine) 目录号 : GC49639An indole alkaloid with analgesic activity
Cas No.:3512-87-6
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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- Purity: >98.00%
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- SDS (Safety Data Sheet)
- Datasheet
Akuammine is an indole alkaloid that has been found in Picralima nitida and has analgesic activity.1 It selectively binds to the μ- and κ-opioid receptors over the δ-opioid receptor (Kis = 0.3, 1.68, and 10.4 µM for the human receptors, respectively). Akuammine inhibits forskolin-induced cAMP production in HEK293 cells expressing human μ- or κ-opioid receptors (IC50s = 2.6 and 0.073 µM, respectively). It increases the latency to withdrawal in the tail-flick or hot plate test in mice when administered at a dose of 60 mg/kg.
1.Creed, S.M., Gutridge, A.M., Argade, M.D., et al.Isolation and pharmacological characterization of six opioidergic Picralima nitida alkaloidsJ. Nat. Prod.84(1)71-80(2021)
| Cas No. | 3512-87-6 | SDF | Download SDF |
| 别名 | (-)-Akuammine, Vincamajoridine | ||
| Canonical SMILES | COC([C@@]12[C@]34[C@](N(C5=CC=C(O)C=C54)C)(OC2)[C@](N(C/6)CC3)([H])C[C@H]1C6=C/C)=O | ||
| 分子式 | C22H26N2O4 | 分子量 | 382.5 |
| 溶解度 | DMF: 2 mg/ml,DMSO: 1 mg/ml,Ethanol: insol,PBS (pH 7.2): insol | 储存条件 | -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。 | ||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.6144 mL | 13.0719 mL | 26.1438 mL |
| 5 mM | 0.5229 mL | 2.6144 mL | 5.2288 mL |
| 10 mM | 0.2614 mL | 1.3072 mL | 2.6144 mL |
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| 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 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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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。
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Akuammine and dihydroakuammine, two indolomonoterpene alkaloids displaying affinity for opioid receptors
J Nat Prod 1992 Mar;55(3):380-4.PMID:1317407DOI:10.1021/np50081a017.
Akuammine [1], an indolomonoterpene alkaloid, which is the major component of the seeds of Picralima nitida, was reduced to dihydroakuammine [4]. This compound has structural analogy with eseroline [7], for which affinity for opiate receptors was reported. The present investigation showed that 1 and 4 also bind (with lower affinity however) to mu and kappa opiate receptors. 1H- and 13C-nmr spectra of 1 and 4 have been fully assigned by 2D nmr experiments.
Isolation and Pharmacological Characterization of Six Opioidergic Picralima nitida Alkaloids
J Nat Prod 2021 Jan 22;84(1):71-80.PMID:33326237DOI:10.1021/acs.jnatprod.0c01036.
The seeds of the akuamma tree (Picralima nitida) have been used as a traditional treatment for pain and fever. Previous studies have attributed these effects to a series of indole alkaloids found within the seed extracts; however, these pharmacological studies were significantly limited in scope. Herein, an isolation protocol employing pH-zone-refining countercurrent chromatography was developed to provide six of the akuamma alkaloids in high purity and quantities sufficient for more extensive biological evaluation. Five of these alkaloids, Akuammine (1), pseudo-akuammigine (3), akuammicine (4), akuammiline (5), and picraline (6), were evaluated against a panel of >40 central nervous system receptors to identify that their primary targets are the opioid receptors. Detailed in vitro investigations revealed 4 to be a potent kappa opioid receptor agonist, and three alkaloids (1-3) were shown to have micromolar activity at the mu opioid receptor. The mu opioid receptor agonists were further evaluated for analgesic properties but demonstrated limited efficacy in assays of thermal nociception. These findings contradict previous reports of the antinociceptive properties of the P. nitida alkaloids and the traditional use of akuamma seeds as analgesics. Nevertheless, their opioid-preferring activity does suggest the akuamma alkaloids provide distinct scaffolds from which novel opioids with unique pharmacologic properties and therapeutic utility can be developed.
Modified Akuamma Alkaloids with Increased Potency at the Mu-opioid Receptor
J Med Chem 2023 Mar 9;66(5):3312-3326.PMID:PMC10037270DOI:10.1021/acs.jmedchem.2c01707.
Akuammine (1) and pseudoakuammigine (2) are indole alkaloids found in the seeds of the akuamma tree (Picralima nitida). Both alkaloids are weak agonists of the mu opioid receptor (μOR); however, they produce minimal effects in animal models of antinociception. To probe the interactions of 1 and 2 at the opioid receptors, we have prepared a collection of 22 semisynthetic derivatives. Evaluation of this collection at the μOR and kappa opioid receptor (κOR) revealed structural-activity relationship trends and derivatives with improved potency at the μOR. Most notably, the introduction of a phenethyl moiety to the N1 of 2 produces a 70-fold increase in potency and a 7-fold increase in selectivity for the μOR. The in vitro potency of this compound resulted in increased efficacy in the tail-flick and hot-plate assays of antinociception. The improved potency of these derivatives highlights the promise of exploring natural product scaffolds to probe the opioid receptors.
Opioid activity of alkaloids extracted from Picralima nitida (fam. Apocynaceae)
Eur J Pharmacol 1998 May 29;350(1):101-8.PMID:9683021DOI:10.1016/s0014-2999(98)00232-5.
Extracts of the seeds of Picralima nitida (fam. Apocynaceae) have been reported to have opioid analgesic activity. In this investigation, isolated tissue bioassays and radioligand binding assays have been used to determine the opioid activity of five alkaloids--akuammidine, Akuammine, akuammicine, akuammigine and pseudoakuammigine--extracted from the seeds of P. nitida. Akuammidine showed a preference for mu-opioid binding sites with Ki values of 0.6, 2.4 and 8.6 microM at mu-, delta- and kappa-opioid binding sites, respectively. The agonist actions of akuammidine in the mouse-isolated vas deferens were antagonised by naloxone and the mu-opioid receptor selective antagonist D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP) confirming an action at mu-opioid receptors. In contrast, Akuammine also showed highest affinity for mu-opioid binding sites (Ki 0.5 microM) but was an antagonist at mu-opioid receptors with a pK(B) of 5.7 against the selective mu-opioid receptor agonist [D-Ala2,MePhe4,Gly-ol5]enkephalin (DAMGO). Akuammicine has the highest affinity for kappa-opioid binding sites (Ki 0.2 microM) and was a full agonist at kappa-opioid receptors in the guinea pig ileum preparation but a partial kappa-opioid receptor agonist in the vasa deferentia of the mouse and the rabbit. Akuammigine and pseudoakuammigine showed little or no efficacy in the opioid bioassays. None of the alkaloids had significant activity for opioid receptor-like binding sites (ORL1-binding sites) with Ki values >> 10 microM. These data show that some alkaloids extracted from the medicinal plant P. nitida possess varying degrees of agonist and antagonist activity at opioid receptors but possess neither high affinity nor selectivity for mu-, delta- or kappa-opioid receptors or the ORL1-receptor.
Alkaloids of Vinca major cv. Variegata
Planta Med 1982 Feb;44(2):91-3.PMID:17402086DOI:10.1055/s-2007-971409.
Analysis of the leaves of Vinca major L. cv. Variegata led to the isolation of seven alkaloids: reserpinine, majdine, akuammicine, strictosidine lactam, pseudoakuammigine, Akuammine, and a new alkaloid tentatively assigned as 10-hydroxycathofoline. The yellowish and green laminar sections of the leaves did not differ in their alkaloid profile.