Aconitine is a diester alkaloid with chemical formula Cthirty-fourHforty-sevenNOeleven，It is highly toxic[4]It mainly excites vagus nerve and damages peripheral nerve.The symptoms of poisoning are mainly nervous system and circulatory system, followed by digestive system symptoms. It is the main toxic ingredient in plants such as Sichuan Aconitum, kusnezoffii, and aconite.
Chinese name
Aconitine
Foreign name
Aconitine
Alias
Aconitine
chemical formula
Cthirty-fourHforty-sevenNOeleven
molecular weight
six hundred and forty-five point seven three seven
Hexagonal lamellar crystal.Melting point 204 ℃.Specific rotation:+17.3 º.The aqueous solution reacts alkaline with litmus, pK5.88. It is soluble in absolute ethanol, ether and water, and slightly soluble in petroleum ether.Aconitine belongs to binary ester and is easy to be hydrolyzed.
Aconitine is a diester alkaloid with a sense of spicy (1/10000 solution can produce a sense of spicy). If acetic acid is added to its aqueous solution (1:4000), a few drops of 0.2mol/L potassium permanganate aqueous solution can produce red cluster crystals.Due to the ester bond, the ferric hydroxamate reaction can also be obtained.
The ester bond in the ester alkaloid molecule is the key part to produce toxicity. The amino alcohol produced after hydrolysis has increased hydrophilicity and reduced toxicity.The two ester bonds can be easily removed by heating aconitine in dilute alkaline aqueous solution to generate aconitine.Or heating aconitine in neutral aqueous solution, ester bond is also hydrolyzed.Generally, when its aqueous solution is at 100 ℃, a molecule of acetic acid is removed to generate benzoyl aconitine, which is further heated to 160 ℃~170 ℃ (under pressure), and the benzoate is also hydrolyzed to produce aconitine.The hydrophilicity of benzoyl aconitine and aconitine is stronger than that of aconitine, but the toxicity is much less.Aconitine has almost completely lost its spicy taste, with a bitter taste, and is an amorphous powder.[1]
toxicology data
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Acute oral LD in ratsfifty0.166mg/kg.[1]
Molecular structure data
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Molar refractive index: 163.11
Molar volume (cmthree/mol）：468.2
Isotonic specific volume (90.2K): 1321.1
Surface tension (dyne/cm): 63.3
Polarization (10-24cmthree）：64.66[1]
Storage method
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Sealed with argon gas and kept away from light.
purpose
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It has analgesic effect and is clinically used to relieve cancer pain, especially for digestive system cancer pain;When used externally, it can paralyze peripheral nerve endings and produce local anesthesia and analgesia;It has anti-inflammatory effect and is extremely toxic. It can excite and paralyze sensory nerves and central nerves, cholinergic nerves and respiratory centers, excite cardiac vagus nerves, and directly poison myocardial cells.There is also sweating effect.
Pharmacological action and use
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Effect on heart
The effect of aconitine on isolated and in vivo frogs is that the heart initially slows down the heart rate (atropine can block it), then because of the high stimulation of the heart muscle, the heart rate suddenly increases, the cardiac contractility strengthens, and soon there is a cardiac rhythm disorder, the cardiac contractility weakens, the heart contractions are like mulberries, and the final heartbeat stops.After the guinea pig myocardium was treated with 10 mg/L aconitine perfusate for 15 min, its abnormal action potential began to appear, peaked in 25 min, and could be maintained for 100 min.Especially, it has a significant impact on the T value of the action potential cycle of myocardial cells. 25 minutes after administration, the T value decreases to 1/5 of the average value of the cycle before administration, 1.0 mg/L perfusion, and the 50% repolarization action potential time limit (APD50) and the total action potential time limit (APD100) significantly reduce.When 0.5 g/L inosine solution was added for 30 min, its T value, APD50 and APD100 all recovered significantly.For its therapeutic amount, it can slow down the heart rate, make the pulse soft and weak, and slightly lower the blood pressure (excite the vagus center);The toxic dose can cause arrhythmia such as tachycardia, ventricular fibrillation and flutter in dogs.[2-3]
Immunosuppressive effect
Aconitine has immunosuppressive effect on immune organs and humoral immunity.It can inhibit T cells and their subsets, thus affecting the function of B cells.The best immunosuppressive period was about one week after the drug was used.[3]
Local anesthesia
Aconitine can stimulate the sensory nerve endings of the local skin and mucous membrane, which first excites to produce a sense of itching and burning, then anesthesia and unconsciousness.Aconitine inhibits the conduction of excitatory nerve endings on neuromuscular junction activity and nerve trunk compound potential at first, and can also make the nerve trunk completely lose the ability of excitation and impulse conduction at high concentration.[3]
clinical application
1. For the treatment of tachycardia and hypertension: low dose aconitine is effective in the treatment of tachycardia and hypertension, but it is easy to produce toxic reactions and difficult to control.
2. It is a tool drug for studying arrhythmia: use the ventricular fibrillation effect of aconitine to make arrhythmia models to study anti arrhythmia drugs.[3]
Key points of treatment
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1. Toxicological antagonism: the key is to follow the principle of early, sufficient, repeated and maintained atropinization when using atropine, and to conduct cardiac auscultation and ECG examination in time to find heart damage and deal with it quickly.
2. Protection of heart damage: The damage of aconitine poisoning to the heart is mainly caused by exciting the vagus nerve and direct damage to the myocardium, which is clinically manifested as various arrhythmias and conduction block.Ventricular premature beats are often seen as multiple sources and multiform, and ventricular premature dual rhythm and triple rhythm are also common;Lidocaine is effective in the treatment of ventricular premature beats.
3. Treatment of complications: The key to the treatment of complications is to correctly deal with the contradictions between pulmonary edema, brain edema, arrhythmia and dilution of toxins.Massive infusion is one of the rescue measures. On the one hand, patients need to supplement calories and electrolytes when fasting, and on the other hand, it can dilute toxins.[2]
security information
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Safety terminology
S24：Avoid contact with skin。
Avoid skin contact.
S45：In case of accident or if you feel unwell, seek medical advice immediately (show the label whenever possible.)。
In case of accident or discomfort, seek medical advice immediately (show the label if possible).
Risk terminology
R26/28：Very toxic by inhalation and if swallowed。
Very toxic if inhaled or swallowed.
matters needing attention
1. Processed products are not allowed for internal use.
2. Master the indications and prevent abuse.
3. Take strict precautions against excessive use of drugs, and keep a certain interval for the second use of drugs.
4. Do not take it with wine to avoid increased absorption.
5. Patients with liver and kidney disease and myocardial disease should be cautious;The dosage should be reduced for the weak. It is forbidden for those with yin deficiency, fever, atrioventricular block, and pregnant women.[1]
