烏頭鹼

烏頭鹼（aconitine）是一種生物鹼毒素。是常用中藥烏頭屬中所含有的一種化學物質，具強烈毒性，口服 0.2mg 左右即能使人中毒，3-5mg 即可致死。民間常用草烏、川烏等植物來泡製藥酒，但這種藥酒可能是極端危險的，也經常因此出現中毒甚至死亡的情況。

用途

烏頭鹼以前被用作解熱藥和鎮痛藥，但在草藥中的應用仍然有限。狹窄的治療指數使計算合適的劑量很困難。

結構和反應性

附子屬和翠雀屬植物的生物活性分離物被歸類為去甲二萜生物鹼。根據 C18 碳的存在與否進一步細分。烏頭鹼是一種 C19 去甲二萜生物鹼，因為它含有 C18。烏頭鹼幾乎不溶於水，但極易溶於有機溶劑，例如氯仿或乙醚。如果酒精濃度足夠高，烏頭鹼也可溶於乙醇和水的混合物中。

像許多其他生物鹼一樣，烏頭鹼六元環的鹼性氮很容易形成鹽和離子，使其對極性和親脂性結構過血腦屏障。

The acetoxyl group at the c8 position can readily be replaced by a methoxy group, by heating aconitine in methanol, to produce a 8-deacetyl-8-O-methyl derivatives. If aconitine is heated in its dry state, it undergoes a pyrolysis to form pyroaconitine ((1α,3α,6α,14α,16β)-20-ethyl-3,13-dihydroxy-1,6,16-trimethoxy-4-(methoxymethyl)-15-oxoaconitan-14-yl benzoate) with the chemical formula C32H43NO9.

作用

Aconitine can interact with the voltage-dependent sodium-ion channels, which are proteins in the cell membranes of excitable tissues, such as cardiac and skeletal muscles and neurons. These proteins are highly selective for sodium ions. They open very quickly to depolarize the cell membrane potential, causing the upstroke of an action potential. Normally, the sodium channels close very rapidly, but the depolarization of the membrane potential causes the opening (activation) of potassium channels and potassium efflux, which results in repolarization of the membrane potential.

Aconitine binds to the channel at the neurotoxin binding site2 on the alpha subunit. This binding results in a sodium-ion channel that stays open longer. Aconitine suppresses the conformational change in the sodium-ion channel from the active state to the inactive state. The membrane stays depolarized due to the constant sodium influx (which is 10–1000-fold greater than the potassium efflux). As a result, the membrane cannot be repolarized. The binding of aconitine to the channel also leads to the channel to change conformation from the inactive state to the active state at a more negative voltage. In neurons, aconitine increases the permeability of the membrane for sodium ions, resulting in a huge sodium influx in the axon terminal. As a result, the membrane depolarizes rapidly. Due to the strong depolarization, the permeability of the membrane for potassium ions increases rapidly, resulting in a potassium reflux to release the positive charge out of the cell. Not only the permeability for potassium ions but also the permeability for calcium ions increases as a result of the depolarization of the membrane. A calcium influx takes place. The increase of the calcium concentration in the cell stimulates the release of the neurotransmitter acetylcholine into the synaptic cleft. Acetylcholine binds to acetylcholine receptors at the postsynaptic membrane to open the sodium-channels there, generating a new action potential.

Research with mouse nerve-hemidiaphragm muscle preparation indicate that at low concentrations (Lurida terribiles miscent aconita novercae.

Fearsome stepmothers mix lurid aconites.

Aconitine was also made famous by its use in Oscar Wilde's 1891 story "Lord Arthur Savile's Crime". Aconite also plays a prominent role in James Joyce's Ulysses, in which the father to protagonist Leopold Bloom used pastilles of the chemical to commit suicide. Aconitine poisoning plays a key role in the murder mystery Breakdown by Jonathan Kellerman (2016). In Twin Peaks (season 3) Part 13, aconitine is suggested to poison the main character.

Monk's Hood is the name of the third Cadfael Novel written in 1980 by Ellis Peters. The novel was made into an episode of the well known television series Cadfael starring Derek Jacobi.

毒性

烏頭鹼的毒性作用已在多種動物身上進行了測試有效，包括哺乳動物（狗、貓、豚鼠、小鼠、大鼠和兔子）、鴿、青蛙。觀察到的毒性作用有：區域性麻醉、腹瀉、抽搐、心律失常、死亡。

根據對人類附子中毒的不同報導的回顧，觀察到以下臨床特徵：

神經系統：感覺異常和臉、口周區域和四肢麻木、肌肉無力。
心血管：低血壓、心悸、胸痛、心動過緩、竇性心動過速、室性異位及其他心律失常、室性心律失常、交界性心律
胃腸道：噁心、嘔吐、腹痛、腹瀉
其他：頭暈、過度換氣、出汗、呼吸困難、意識模糊、頭痛、流淚

烏頭鹼中毒的最初症狀出現在口服後約 20 分鐘至 2 小時，包括感覺異常、出汗、噁心。這會導致嚴重的嘔吐、絞痛性腹瀉、劇烈疼痛，然後骨骼肌麻痺。威脅生命的心律失常，包括室性心動過速、心室顫動，會因呼吸麻痺或心臟驟停而死亡。

小鼠的值為口服 1 mg/kg、靜脈 0.100 mg/kg、腹膜 0.270 mg/kg 和皮下 0.270 mg/kg。小鼠的最低致死量為口服 1 mg/kg 和腹腔 0.100 mg/kg。小鼠的最低中毒量為 0.0549 mg/kg 皮下注射。大鼠靜脈注射的值為 0.064 mg/kg。大鼠的為靜脈注射 0.040 mg/kg 和腹腔 0.250 mg/kg。大鼠的腸胃為 0.040 mg/kg。有關更多參見下表：表示平均致死量；是指最低致死量；表示最低中毒量。

對於人類，1969 年報導的最低口服致死劑量為 28 μg/kg。

烏頭鹼（草烏、川烏）中毒在急診及內科中常見，多因服用自制中藥及自制藥膳不當所致。

它主要使迷走神經興奮，對周圍神經損害臨床主要表現為口舌及四肢麻木，全身緊束感等，透過興奮迷走神經而降低竇房結的自律性，引起異位起搏點的自律性增高而引起各心律失常，損害心肌。

臨床作用