CN102552254A - Application of bulleyaconitine A used as state-independent sodium ion channel blocker to analgesia - Google Patents
Application of bulleyaconitine A used as state-independent sodium ion channel blocker to analgesia Download PDFInfo
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- CN102552254A CN102552254A CN201210025825XA CN201210025825A CN102552254A CN 102552254 A CN102552254 A CN 102552254A CN 201210025825X A CN201210025825X A CN 201210025825XA CN 201210025825 A CN201210025825 A CN 201210025825A CN 102552254 A CN102552254 A CN 102552254A
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Abstract
The invention discloses application of bulleyaconitine A (BLA) used as a state-independent sodium ion channel blocker to the analgesia, and relates to application of a medicine, in particular to application of aconitine alkaloids to the analgesia. The application of the bulleyaconitine A used as the state-independent sodium ion channel blocker to the analgesia is characterized in that the BLA only blocks a neuron sodium ion channel in an open state in a state dependence way, and does not interact with a neuron sodium ion channel in a resting state or an inactivation state. Compared with other analgesic medicines, the medicine in which the bulleyaconitine A is taken as an active ingredient has the advantage that the analgesic side effect is relatively small.
Description
Technical field
The present invention relates to a kind of medicinal application, the application of especially a kind of aconitine-type alkaloids in analgesia.
Background technology
For hundreds of years, the root of aconitum plant is widely used in anesthesia, rheumatism and effects on neural system in China and Japanese the world of medicine.Separating the alkaloid that obtains in the aconitum plant has 10 kinds more than, comprises various " type aconitines " and " type lappaconitine " diterpene-kind compound.In these two kinds of Diterpenes alkaloid bodies very strong narcotic activity is arranged all.In addition; Lappaconitine also has the effect of irreversible block N a ion current, and aconitine not only can reduce the sodium ion electric current, and the sodium-ion channel that activation voltage relies under the hyperpolarization condition; Causing the appearance of sodium ion valve electric current, is " activator " of sodium-ion channel.The result of voltage transitions in this activation process, aconitine can cause the reignition of neurocyte, hyperesthesia and arrhythmia.
Bulleyaconitine A (BLA) is the diterpene diester-type aconitine-type alkaloids that separation and Extraction goes out in the aconitum plant tap Aconitum carmichjaelii Debx., is the active component in the Aconitum.With respect to for, the sodium ion valve current ratio aconitine that bulleyaconitine A causes under same concentrations will lack a lot.In China, BLA has ratified to be used for the treatment of chronic pain and rheumatoid arthritis, but its mechanism of action is still indeterminate.
Summary of the invention
To be solved by this invention is exactly the problem that at present bulleyaconitine A deep analgesic activity mechanism, biopharmaceutics character and pharmacokinetics characteristic it be unclear that; Further probe into the analgesic activity principle of bulleyaconitine A; Investigate the analgesic activity of bulleyaconitine A through the animal model of setting up neuropathic pain; And pass through analgesic mechanism, thereby find therapeutic effect and the timeliness thereof of bulleyaconitine A to the neuropathic pain animal pattern to the research exploration bulleyaconitine A of sodium-ion channel and TNF-a.
Bulleyaconitine A of the present invention is as the application of sodium ion blocker in analgesia of state dependence; It is characterized in that the only neuron sodium-ion channel of the blocking-up open state of state dependence of BLA, do not interact with the neuron sodium-ion channel of quiescent condition or inactivated state.
The concentration of described BLA is 10 μ mol/L.
That discovers pain is produced as tissue injury through acting on cell membrane like destructive stimulus machinery, temperature, chemistry; And this stimulation is converted into neural impulse or action potential; It is neuronic ectopic discharge; The first order neuron DRG (dorsal root ganglia) that imports into through the pain sensation is a dorsal root ganglion, uploads to the process of maincenter again.Neuronic ectopic discharge flows in a large number just because of the outer Na+ of cell membrane and causes in the cell membrane, therefore, if can suppress the interior stream of Na+, plays the generation of retardance electric current, then can reach the analgesic effect.
And bulleyaconitine A can act on the Na+ passage, is the Na+ blocker of state dependence, promptly only Na+ passage under the state of activation is had effect, and to the Na+ passage of tranquillization and inactivated state less than influencing.With respect to other analgesic; Like lignocaine, though it also acts on the Na+ passage, it still has inhibitory action to the Na+ passage of tranquillization and inactivated state; Be still can produce inhibition under the normal condition particularly at quiescent condition; Therefore the analgesic also can cause the generation of side effect simultaneously, thereby lignocaine is used for local application more, and is not used in the reason of general administration.
In addition, the analgesics gabapentin is the Ca2+ channel inhibitor, and action site can suppress to be caused in the Ca2+ of gray nucleus cornu dorsale by nerve injury and flow on P/Q type Ca2+ passage, mainly acts on cental system, the treatment neuropathic pain, and irrelevant with periphery.
Description of drawings
Fig. 1 is the bulleyaconitine A of 10 μ M and the action current trajectory diagram of quiescent condition or inactivated state neuron sodium-ion channel.
The action current trajectory diagram of the bulleyaconitine A of Fig. 2 formula 10 μ M and aconitine and state of activation neuron sodium-ion channel.
The specific embodiment
Embodiment 1: bulleyaconitine A is as the application of sodium ion blocker in analgesia of state dependence, and through accompanying drawing and three experimental grouies, quiescent condition experimental group, inactivated state group and state of activation group are done further explanation to the present invention.
Figure 1A is before and after the bulleyaconitine A effect 5min of 10 μ M, the current locus of sodium ion under the quiescent condition.The control current potential is at-140mV, and maintenances sodium-ion channel is a quiescent condition, with single pulse voltage+50 mV, continues 3ms, embedding, and every 30s stimulation is once.Show among the figure that after the BLA effect, the sodium ion electric current does not reduce, therefore, BLA does not have blocking effect to Na passage under the quiescent condition.
Figure 1B is before and after the bulleyaconitine A effect 5min of 10 μ M, the current locus of sodium ion under the inactivated state.The control current potential continues 10s at-70mV, and to make sodium-ion channel depolarization (embedding) be inactivation.The overlapping track of sodium ion electric current is with single test pulse record in addition.Show among the figure that after the BLA effect, inactivated state sodium ion electric current does not reduce.Interpulse-140mV, continue 100ms, embed, the sodium-ion channel of the inactivation of medicine effect is recovered, before test pulse, use, same, the blocking-up of the inactivation that BLA causes is seldom.Therefore, BLA does not have blocking effect to Na passage under the inactivated state.
Fig. 2 A be sodium-ion channel at 2HZ, 1000 repetition pulse+50 mV continue 4ms effect activation down, before repetition pulse, cell causes the repetition track of sodium ion electric current with the bulleyaconitine A lavation 5min of 10 μ M.From 1p to 1000p, visible, the p value is big more, and the sodium ion electric current reduces many more, and visible, under state of activation, BLA has blocking effect to sodium-ion channel.
Fig. 2 B condition is with Fig. 2 A, is the repetition track of the sodium ion electric current that causes of the aconitine of 10 μ M.It is thus clear that, the same with BLA, the blocking-up sodium ion electric current of aconitine state dependence, but the inhibition degree is not so good as BLA, and the follow-up threshold current that causes is big more a lot of than BLA.
Therefore, bulleyaconitine A (BLA) is the neuron sodium-ion channel of the blocking-up open state of state dependence only, does not interact with the neuron sodium-ion channel of quiescent condition or inactivated state.
Claims (1)
1. bulleyaconitine A of the present invention is as the application of sodium ion blocker in analgesia of state dependence; It is characterized in that the only neuron sodium-ion channel of the blocking-up open state of state dependence of BLA, do not interact with the neuron sodium-ion channel of quiescent condition or inactivated state.
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| CN201210025825XA CN102552254A (en) | 2012-02-07 | 2012-02-07 | Application of bulleyaconitine A used as state-independent sodium ion channel blocker to analgesia |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109453169A (en) * | 2018-11-19 | 2019-03-12 | 云南昊邦制药有限公司 | The purposes of bulleyaconitine A |
| CN113149905A (en) * | 2021-02-24 | 2021-07-23 | 成都中医药大学 | Low-toxicity antiarrhythmic compound and pharmaceutical application thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101480393A (en) * | 2008-01-07 | 2009-07-15 | 云南昊邦制药有限公司 | Application of bulleyaconitine A in preparing medicament for treating Nav1.7 ache disease |
| CN101480392A (en) * | 2008-01-07 | 2009-07-15 | 云南昊邦制药有限公司 | Application of bulleyaconitine A in preparing medicament for treating ache related to sodium channel |
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2012
- 2012-02-07 CN CN201210025825XA patent/CN102552254A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101480393A (en) * | 2008-01-07 | 2009-07-15 | 云南昊邦制药有限公司 | Application of bulleyaconitine A in preparing medicament for treating Nav1.7 ache disease |
| CN101480392A (en) * | 2008-01-07 | 2009-07-15 | 云南昊邦制药有限公司 | Application of bulleyaconitine A in preparing medicament for treating ache related to sodium channel |
Non-Patent Citations (1)
| Title |
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| 王锋鹏: "从草乌化学研究开发的新药思考中药现代化的方法", 《化学进展》, vol. 21, no. 01, 31 January 2009 (2009-01-31) * |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109453169A (en) * | 2018-11-19 | 2019-03-12 | 云南昊邦制药有限公司 | The purposes of bulleyaconitine A |
| WO2020103435A1 (en) * | 2018-11-19 | 2020-05-28 | 云南昊邦制药有限公司 | Use of bulleyaconitine a |
| CN109453169B (en) * | 2018-11-19 | 2021-05-14 | 云南昊邦制药有限公司 | Application of bulleyaconitine A |
| KR20210090236A (en) * | 2018-11-19 | 2021-07-19 | 윈난 하오피 파마슈티컬스 엘티디 | Uses of Bulliaconitin A |
| JP2022507646A (en) * | 2018-11-19 | 2022-01-18 | ユンナン ハオピィ ファーマシューティカルズ エルティーディー | Uses of braiaconitine A |
| JP7190571B2 (en) | 2018-11-19 | 2022-12-15 | ユンナン ハオピィ ファーマシューティカルズ エルティーディー | Uses of Bray Aconitine A |
| KR102610339B1 (en) | 2018-11-19 | 2023-12-07 | 윈난 하오피 파마슈티컬스 엘티디 | Uses of Buliaconitin A |
| CN113149905A (en) * | 2021-02-24 | 2021-07-23 | 成都中医药大学 | Low-toxicity antiarrhythmic compound and pharmaceutical application thereof |
| CN113149905B (en) * | 2021-02-24 | 2022-04-29 | 成都中医药大学 | Compound for resisting arrhythmia and pharmaceutical application thereof |
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Application publication date: 20120711 |