Bulleyaconitine A
(Synonyms: 草乌甲素) 目录号 : GC35568
Bulleyaconi cine A (Bulleyaconitine A, BLA) is an active ingredient of Aconitum bulleyanum plants and classified as an "aconitine-like" alkaloid. It is a potent use-dependent blocker for both Nav1.7 and Nav1.8 Na+ currents.
Cas No.:107668-79-1
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
Bulleyaconi cine A (Bulleyaconitine A, BLA) is an active ingredient of Aconitum bulleyanum plants and classified as an "aconitine-like" alkaloid. It is a potent use-dependent blocker for both Nav1.7 and Nav1.8 Na+ currents.
| Cas No. | 107668-79-1 | SDF | |
| 别名 | 草乌甲素 | ||
| Canonical SMILES | O=C(C1=CC=C(OC)C=C1)C2C3(O)C(OC)CC4(OC(C)=O)C2C(C3)C56C(C(OC)C4C6N(CC)C7)C7(COC)CCC5OC | ||
| 分子式 | C35H49NO9 | 分子量 | 627.76 |
| 溶解度 | DMSO: 125 mg/mL (199.12 mM) | 储存条件 | Store at 2-8°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 | 1.593 mL | 7.9648 mL | 15.9297 mL |
| 5 mM | 0.3186 mL | 1.593 mL | 3.1859 mL |
| 10 mM | 0.1593 mL | 0.7965 mL | 1.593 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。
Mechanisms for therapeutic effect of Bulleyaconitine A on chronic pain
Mol Pain 2018 Jan-Dec;14:1744806918797243.PMID:30180777DOI:10.1177/1744806918797243.
Bulleyaconitine A, a diterpenoid alkaloid isolated from Aconitum bulleyanum plants, has been used for the treatment of chronic pain in China since 1985. Clinical studies show that the oral administration of Bulleyaconitine A is effective for treating different kinds of chronic pain, including back pain, joint pain, and neuropathic pain with minimal side effect in human patients. The experimental studies have revealed that Bulleyaconitine A at therapeutic doses potently inhibits the peripheral sensitization and central sensitization that underlie chronic pain and has no effect on acute pain. Bulleyaconitine A preferably blocks tetrodotoxin-sensitive voltage-gated sodium channels in dorsal root ganglion neurons by inhibition of protein kinase C, and the effect is around 600 times more potent in neuropathic animals than in naïve ones. Bulleyaconitine A at 5 nM inhibits the hypersensitivity of dorsal root ganglion neurons in neuropathic rats but has no effect on excitability of dorsal root ganglion neurons in sham group. Bulleyaconitine A inhibits long-term potentiation at C-fiber synapses in spinal dorsal horn, a synaptic model of pathological pain, preferably in neuropathic pain rats over naïve rats. The following mechanisms may underlie the selective effect of Bulleyaconitine A on chronic pain. (1) In neuropathic conditions, protein kinase C and voltage-gated sodium channels in dorsal root ganglion neurons are upregulated, which enhances Bulleyaconitine A's effect. (2) Bulleyaconitine A use-dependently blocks voltage-gated sodium channels and therefore inhibits the ectopic discharges that are important for neuropathic pain. (3) Bulleyaconitine A is shown to inhibit neuropathic pain by the modulation of spinal microglia, which are involved in the chronic pain but not in acute (nociceptive) pain. Moreover, Bulleyaconitine A facilitates the anesthetic effect of morphine and inhibits morphine tolerance in rats. Together, Bulleyaconitine A is able to inhibit chronic pain by targeting at multiple molecules. Further clinical and experimental studies are needed for evaluating the efficacy of Bulleyaconitine A in different forms of chronic pain in patients and for exploring the underlying mechanisms.
Bulleyaconitine A is a sensitive substrate and competitive inhibitor of CYP3A4: One of the possible explanations for clinical adverse reactions
Toxicol Appl Pharmacol 2022 Jun 15;445:116024.PMID:35439480DOI:10.1016/j.taap.2022.116024.
Bulleyaconitine A (BLA), a toxic Aconitum alkaloid, is a potent analgesic that is clinically applied to treat rheumatoid arthritis, osteoarthritis and lumbosacral pain. BLA-related adverse reactions occur frequently, but whether the underlying mechanism is related to its metabolic interplay with drug-metabolizing enzymes remains unclear. This study aimed to elucidate the metabolic characteristics of BLA and its affinity action and mechanism to drug-metabolizing enzymes to reveal whether BLA-related adverse reactions are modulated by enzymes. After incubation with human liver microsomes and recombinant human cytochrome P450 enzymes, we found that BLA was predominantly metabolized by CYP3A, in which CYP3A4 had an almost absolute advantage. In vitro, the CYP3A4 inhibitor ketoconazole noticeably suppressed the metabolism of BLA. In vivo, the AUC0-∞ values, cardiotoxicity and neurotoxicity of BLA in Cyp3a-inhibited mice were all obviously enhanced (P < 0.05) compared to those in normal mice. In the enzyme kinetics study, BLA was found to be a sensitive substrate of CYP3A4, and its characteristics were consistent with substrate inhibition (Km = 39.36 ± 10.47 μmol/L, Ks = 83.42 ± 19.65 μmol/L). BLA was further identified to be a competitive inhibitor of CYP3A4 with Ki = 53.64 μmol/L, since the intrinsic clearance (CLint) of midazolam, a selective CYP3A4 substrate, decreased significantly (P < 0.05) when incubated with BLA together in mouse liver microsomes. Overall, BLA is a sensitive substrate and competitive inhibitor of CYP3A4, and clinical adverse reactions of BLA may mechanistically related to the CYP3A4-mediated drug-drug interactions.
Bulleyaconitine A Exerts Antianxiety and Antivisceral Hypersensitivity Effects
Front Pharmacol 2020 Mar 19;11:328.PMID:32265706DOI:10.3389/fphar.2020.00328.
Visceral pain is one of the leading causes for abdominal pain in gastroenterological diseases and is still hard to treat effectively. Bulleyaconitine A (BAA) is an aconitine analog and has been used for the treatment of pain. Our previous work suggested that BAA exerted analgesic effects on neuropathic pain through stimulating the expression of dynorphin A in spinal microglia. Here, we investigated the inhibitory effect of BAA on visceral pain and examined whether the expression of dynorphin A in spinal microglia was responsible for its effects. We found that BAA produced significant antivisceral pain effect induced by acetic acid through stimulating dynorphin A expression in spinal microglia. In addition, anxiety and chronic visceral pain are highly prevalent comorbid conditions in clinical research, which is still a problem to be solved. We also aimed to evaluate the effects of BAA on anxiety. A comorbidity model with characteristics of both chronic visceral pain and anxiety was developed by colorectal injection of 2,4,6-trinitrobenzene sulfonic acid and the induction of heterotypic intermittent chronic stress protocol. In comorbid animals, BAA exerted great antianxiety effects. Meanwhile, the antianxiety mechanism of BAA was different with the antivisceral pain mechanism of BAA. In conclusion, our study demonstrated, for the first time, that BAA exerted marked antivisceral pain and antianxiety effects, which expands the analgesic spectrum and clinical application of BAA. Furthermore, it also it provides a better guidance for the clinical use of BAA.
Synthesis and Evaluation of a Series of New Bulleyaconitine A Derivatives as Analgesics
ACS Omega 2020 Aug 17;5(33):21211-21218.PMID:32875257DOI:10.1021/acsomega.0c02944.
As a nonaddictive analgesic widely used in clinics, the LD50 of Bulleyaconitine A is just only 0.92 mg/kg, which exhibits obvious toxicity. Therefore, 31 new non-natural C19-diterpenoid alkaloids (2a-w, 2'a-e, 3, 4a, and 4b) were designed and synthesized from Bulleyaconitine A to develop nonaddictive analgesics with low toxicity. The chemical structures were characterized by 1H NMR, 13C NMR, and high-resolution mass spectrometry (HRMS) spectra. The analgesic activities were evaluated by a hot plate test in mice. At the dosage of 10 mg/kg, six compounds (2d, 2j, 2k, 2m, 2t, 2w) exhibited good analgesic activities (increased pain threshold >100%) with a long duration. Among them, 2w showed the best analgesic activity and the longest duration. Its pain threshold reached 166.35% in 15 min, peaked at 30 min (182.35%), and remained 82.59% even at 60 min.
[Clinical efficacy of Bulleyaconitine A combined with gabapentin on postherpetic neuralgia]
Zhonghua Yi Xue Za Zhi 2021 Nov 23;101(43):3575-3580.PMID:34808751DOI:10.3760/cma.j.cn112137-20210817-01867.
Objective: To investigate the analgesic efficacy and safety of state-dependent sodium channel blocker-bulleyaconitine combined with calcium channel blocker-gabapentin on postherpetic neuralgia (PHN). Methods: A double-blind, randomized, placebo-controlled, parallel-group, multi-center study involving Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Qinghai Provincial People's Hospital, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine, the Second Affiliated Hospital of Kunming Medical University was performed from September 2018 to December 2019. A total of 75 PHN patients were randomly divided into the experiment group (n=41) and the control group (n=34). On the basis of first-line treatment with gabapentin, the experiment group was given Bulleyaconitine A tablets, while the control group was given placebo. The primary outcome was a 50% improvement in the visual analogue scale (VAS), and the effective rate of achieving the primary outcome between the two groups was compared; the Cox regression model was used to analyze the impact of related factors on the disease outcome. Secondary outcomes including scores of pain scales (ID-pain, DN4), Patient Health Questionnaire (PHQ-9), 7-item Generalized Anxiety Disorder (GAD-7) at 1, 2, 3, 4, 8, 12 weeks after treatment were applied to evaluate the efficacy and safety of the combination of Bulleyaconitine A tablets with first-line drug in the treatment of PHN. Results: The effective rate was 68.3% (28/41) and the time reached the primary outcome was 28 (7, 84) days in the experiment group, while in the control group, the effective rate was 52.9% (18/34) and the time reached the primary outcome was 56 (14, 84) days. Cox regression analysis indicated that the grouping factor of oral Bulleyaconitine A tablets was an independent factor for improving the outcome of PHN (HR=2.063, 95%CI: 1.059-4.018, P<0.05), and the probability of the experiment group reaching the primary outcome was 2.063 times that of the control group (P<0.05). Meanwhile, the outcome probability of the long disease course group (>6 months) was only 0.201 times that of the short disease course group (<6 months) (HR=0.201, 95%CI: 0.073-0.551, P<0.05). There was no statistically significant difference in the trend of VAS between the two groups (P>0.05). The scores of ID-pain, DN4, PHQ-9, and GAD-7 of the two groups were significantly improved compared with those before enrollment (P<0.05), but the differences between the two groups were not statistically significant (all P>0.05). Conclusion: Bulleyaconitine A tablet can promote the therapeutic efficacy of gabapentin, and improve the outcome of PHN in a short period of 3 months.