Structural characterization, in vivo toxicity and biological activity of two new pyro-type diterpenoid alkaloids derived from 3-acetylaconitine / 中西医结合学报

OBJECTIVE@#The transformations that occur in diterpenoid alkaloids during the process of sand frying for Chinese herbal medicine preparation have yet to be clarified. This study investigated the structural changes that take place in 3-acetylaconitine during a simulation of heat-processing and evaluated the toxicity and biological activity of the pyrolysis products.@*METHODS@#The diterpenoid alkaloid 3-acetylaconitine was heated at 180 °C for 15 min to simulate the process of sand frying. The pyrolysis products were separated using column chromatography, and their structures were investigated using high-resolution electrospray ionization mass spectroscopy and nuclear magnetic resonance spectroscopy. Further, in vivo cardiotoxicity and acute toxicity of 3-acetylaconitine and its pyrolysis products were compared, and the aconitine-induced arrhythmia model was employed to evaluate the antiarrhythmic effect of the pyrolysis products.@*RESULTS@#Two new diterpenoid alkaloids, pyroacetylaconitine and 16-epi-pyroacetylaconitine, a pair of epimers at C-16, were isolated. After comparing the structures of these compounds, possible transformation pathways were proposed. Compared with the prototype compound, 3-acetylaconitine, the cardiotoxicity and acute toxicity of the heat-transformed products were significantly decreased. In the biological activity assay, the two pyrolysis products exhibited an effective increase in ventricular premature beat latency, a reduction in the occurrence of ventricular tachycardia, as well as an increase in the rate of arrhythmia inhibition, implying strong antiarrhythmic activity.@*CONCLUSION@#Compared with 3-acetylaconitine, its pyrolysis products displayed lower toxicity and good antiarrhythmic effects; thus, they have potential for being developed into antiarrhythmic medicines. Please cite this article as: Wang YJ, Wang Y, Tao P. Structural characterization, in vivo toxicity and biological activity of two new pyro-type diterpenoid alkaloids derived from 3-acetylaconitine. J Integr Med. 2023; 21(3): 302-314.

A case report with the coincidental complication of paroxysmal atrial fibrillation in the course of methadone administration due to cancer pain

Introduction: Paroxysmal atrial fibrillation (Paf) occurred in an inpatient who has been prescribed methadone for cancer pain in our palliative care unit, but oral administration of aprindine (antiarrhythmic agent) succeeded in defibrillation and methadone administration could be continued. Case: A 75-year-old man had developed multiple bone metastases after resection of thyroid cancer. Due to refractory cancer pain, switching from oxycodone to methadone was performed. Pain relief was achieved with methadone 40 mg/day and without QT interval prolongation. After methadone administration about 9 months, there suddenly became loss of appetite in the morning of one day. ECG examination revealed Paf onset. Aprindine 20 mg was orally administered for the purpose of defibrillation. After about 2 hours sinus rhythm was gained and later without recurrence. Conclusion: This case was considered to have the coincidental complication of paroxysmal atrial fibrillation in the course of methadone administration. If administration of antiarrhythmic agents is performed in a patient whom has been prescribed methadone, it is feared to lead to result in QT interval prolongation due to drug interactions. It is important to carefully select an agent that rarely leads to QT prolongation.

Comparision of thr Efficacy of Propafenone and Flecainide in Patients with Atrial Fibrillation

BACKGROUND: Atrial fibrillation is one of the most common cardiac arrhythmias which has been recieved relatively little attention until recently.Despite the variety of treatment modalities including drugs,surgery,catheter ablation and devices,the overall treatment of atrial fibrillation is not always satisfactory.Phalmacotherapy is still the most commonly used treatment through the unfavorable side effects of antiarrhythmic drugs are problematic.The purpose of this study is to compare the efficacy of class Ic antiarrhythmic drugs,propafenone versus flecainide. METHODS: We treated one hundred eighteen patients with atrial fibrillation by class Ic antiarrhythmic drugs,propafenone or flecainide with/without DC cardioversion to convert to and maintain the sinus rythm. We compared the clinical findings,drug efficacy,side sffects of drugs between two groups. RESULTS: 30 patients were treated by propafenne and 88 patients by flecainide.21 and 60 patients in each group were lone atrial fibrillation,14 and 49 patients were paroxysmal atrial fibrillation.Mean duration of drug administration were 360.9,339.4 days,respectively.The convesion rate to sinus rhythm by drugs was 25.0% in propafenone group and 30.7% in flecainide group(p=NS).The 300 days-manitenance rates of sinus rhythm after conversion by drugs or DC cardioversion were 63,3%,70.4%(p=NS)respectively. The side effects of drugs were dizziness,nausia and vomitting in both group and 1st degree AV block,transient sinus node dysfunction and decreased visual acuity in flecainde group.The drugs were discontinued in 11(37.7%) and 26(29.5%) patients in each group due to recurrence of atrial fibrillation or side effects of drugs. CONCLUSION: This study suggests that propafenone and flecainide are comparably effective in maintaining sinus rhythm in atrial fibrillation patients.Futher prospective and large study is required to confirm this findings.

ANTIARRHYTHMIC EFFECT OF TOTAL FLAVONES OF HIPPOPHASE RHAMNOIDES IN THE ISOLATED HEART / 中国药理学通报

In the isolated perfused rat heart, TFH counteracted significantly the arrhythmias caused by perfusing with a solution without oxygen; increased ventricular fibrillation threshold markedly and showed a good dose-effective relation; prolonged the P-R period of electrocardiogram and decreased the heart rate and fell the amplitude of cardiac contraction markedly; and counteracted significantly the decrease of the heart rate and the amplitude of cardiac contraction caused by perfusing with a solution without oxygen. In the isolated guinea pig left atrium, TFH prolonged the function refractory period slightly. In the isolated guinea pig right atrium, TFH increased the accumulated dose of aconitine inducing arrhythmias.