普鲁卡因胺 | 51-06-9

• 物质功能分类: 原料药 - 循环系统用药 - 抗心律失常药
• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 普鲁卡因胺
• 中文别名: 4-氨基-N-[2-(二乙基氨基)乙基]苯甲酰胺；4-氨基-n-(2-二乙基氨基乙基)苯甲酰胺；磺胺对甲氧嘧啶；普鲁卡因胺; 4-氨基-N-[2-(二乙基氨基)乙基]苯甲酰胺
• 英文名称: 4-amino-N-(2-diethylaminoethyl)benzamide
• 英文别名: Procainamide；4-amino-N-[2-(diethylamino)ethyl]benzamide
• CAS: 51-06-9
• 化学式: C₁₃H₂₁N₃O
• mdl: MFCD00066880
• 分子量: 235.329
• InChiKey: REQCZEXYDRLIBE-UHFFFAOYSA-N

物化性质

• 熔点：
  47°C
• 沸点：
  377.72°C (rough estimate)
• 密度：
  1.060
• 溶解度：
  氯仿（微溶）、乙酸乙酯（微溶）
• 物理描述：
  Solid
• 保留指数：
  2193;2193;2250;2199.8;2240;2245;2248

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  17
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.461
• 拓扑面积：
  58.4
• 氢给体数：
  2
• 氢受体数：
  3

ADMET

代谢

肝脏的

Hepatic

来源:DrugBank

代谢

药物被血浆酯酶和微粒体酶相对缓慢地水解.../中华人民共和国：通过微粒体酶/

DRUG IS RELATIVELY SLOWLY HYDROLYZED BY PLASMA ESTERASES.../PRC: AND BY MICROSOMAL ENZYMES/

来源:Hazardous Substances Data Bank (HSDB)

代谢

普鲁卡因酰胺在人体和恒河猴口服给药后代谢为N-乙酰衍生物。在猴尿液中检测到两种主要代谢物，对乙酰氨基苯甲酸和脱乙基衍生物，对乙酰氨基-N-[2-(乙氨基)-乙基]苯甲酰胺。

PROCAINAMIDE...WAS METABOLIZED TO N-ACETYL DERIV FOLLOWING ORAL ADMIN TO MAN & RHESUS MONKEYS. ... TWO MAJOR METABOLITES WERE DETECTED IN MONKEY URINE, P-ACETAMIDOBENZOIC ACID & DE-ETHYLATED DERIV, P-ACETAMIDO-N-[2-(ETHYLAMINO)-ETHYL]BENZAMIDE.

来源:Hazardous Substances Data Bank (HSDB)

代谢

N-乙酰普鲁卡因酰胺是普鲁卡因酰胺的活性代谢物。

N-ACETYLPROCAINAMIDE IS AN ACTIVE METABOLITE OF PROCAINAMIDE.

来源:Hazardous Substances Data Bank (HSDB)

代谢

普鲁卡因酰胺已知的人体代谢物包括Acecainide。

Procainamide has known human metabolites that include Acecainide.

来源:NORMAN Suspect List Exchange

毒理性

• 毒性总结

识别：普鲁卡因酰胺是一种抗心律失常药物。盐酸普鲁卡因酰胺是一种白色至棕色的吸湿性无味结晶粉末。溶于水、酒精、氯仿，几乎不溶于醚和苯 人体暴露：主要风险和靶器官：心脏是主要的靶器官。普鲁卡因酰胺是一种用于抑制室性心动过速的抗心律失常剂。它增加了心房的有效不应期，以及（较小程度上）希氏-浦肯野系统束和心室的不应期。毒性效应来自传导延迟和心肌收缩力的抑制，导致心律失常和心源性休克。其口服使用受到免疫不良反应的限制，如慢性口服治疗的患者出现系统性红斑狼疮。 临床效果总结： 心血管系统：窦性或房性心动过速，房室传导阻滞，低血压，心源性休克，尖端扭转型室性心动过速和心室纤颤。 中枢神经系统：嗜睡，昏迷，呼吸暂停可能导致 胃肠系统：恶心，呕吐，腹泻和腹痛有报道。 其他：抗胆碱能作用，低钾血症，代谢性酸中毒和肺水肿。 适应症：抑制室性心律失常。治疗自动性和折返性室上性心动过速。室上性心律失常：与奎尼丁一样，普鲁卡因酰胺在将房扑或慢性房颤转为窦性心律方面仅具有中等效果。药物可用于预防房扑或房颤电复律后的复发。普鲁卡因酰胺用于治疗室性早搏，预防室性心动过速经静脉药物或电复律或其他抗心律失常治疗后转为窦性心律的复发；还用于预防阵发性室上性心动过速、房颤或房扑初步迷走神经操纵、洋地黄制剂、其他药物抗心律失常剂或电复律转为窦性心律后的复发。该药物对利多卡因无效的严重室性心律失常患者有效。普鲁卡因酰胺用于急性终止与WPW综合症相关的心律失常。普鲁卡因酰胺用于全身麻醉患者发生的心律失常的治疗。该药物已与溴化六甲铵联合使用，以产生控制性低血压，并因此产生足够程度的缺血，以进行相对无血的外科手术。将普鲁卡因酰胺注入疼痛的软组织纤维化和放射性神经根炎以及变性关节炎的关节周围组织，可长时间缓解疼痛。 禁忌症：完全性心脏传导阻滞：因其抑制节点或室性起搏器的作用。尖端扭转型室性心动过速：在这种情况下，给予普鲁卡因酰胺可能会加重这种特殊类型的室性早搏或心动过速，而不是抑制它。特异体质超敏反应：在敏感于普鲁卡因或其他酯类局部麻醉剂的患者中，对普鲁卡因酰胺的交叉过敏反应不太可能。然而，对普鲁卡因酰胺的先前过敏反应是禁忌症。红斑狼疮：症状加重的可能性很高。 注意事项：最好不在支气管哮喘或重症肌无力的患者中使用普鲁卡因酰胺。心、肾或肝衰竭的患者可能会出现药物积累。普鲁卡因酰胺可能增强抗高血压药、普萘洛尔和一些骨骼肌松弛剂的效果。严重低血压可能发生在静脉注射普鲁卡因酰胺后；应在监测血压和心电图的情况下缓慢注射。尽管普鲁卡因酰胺已有效地用于治疗由洋地黄中毒引起的室性心律失常，但其效果不可预测，且有死亡发生。普鲁卡因酰胺不应给予哺乳母亲。 进入途径：口服：口服途径是中毒病例中常见的进入途径。肠道外：静脉注射后可能会出现毒性反应。 吸收：口服：普鲁卡因酰胺几乎完全并且迅速从胃肠道吸收。在摄入胶囊后1小时内达到峰值水平，但在服用片剂后稍晚。生物利用度约为85%。过量可能会显著延迟肠道普鲁卡因酰胺的吸收并延长中毒症状。使用缓释制剂时，生物利用度降低，吸收延迟。作用持续时间超过8小时。 肌肉注射：血浆浓度显示出非常大的变化。普鲁卡因酰胺在两分钟内出现在血浆中，并在25分钟内达到峰值浓度。 静脉注射：普鲁卡因酰胺几乎立即起作用，血浆水平每小时下降10至15%。分布：约20%的血浆普鲁卡因酰胺与蛋白结合。普鲁卡因酰胺迅速分布到大多数身体组织，除了大脑。在心脏衰竭或休克的患者中，分布容积可能会减少。普鲁卡因酰胺穿过胎盘屏障，据报道在胎儿中积累。 消除：口服：摄入后1到2小时。肌肉注射：给药后80分钟。静脉注射：几分钟内。治疗剂量后的血浆半衰期为3至4小时。然而，在一个患者中，过量血浆半衰期为8.8小时。充血性心力衰竭将普鲁卡因酰胺的血浆半衰期增加到5至8小时。

IDENTIFICATION: Procainamide is an antiarrhythmic medication. Procainamide hydrochloride is a white to tan colored hygroscopic odorless crystalline powder. Soluble in water, alcohol, chloroform and practically insoluble in ether and benzene HUMAN EXPOSURE: Main risks and target organs: The heart is the main target organ. Procainamide is an antiarrhythmic agent used to suppress ventricular tachydysrhythmias. It increases the effective refractory period of the atria, and (to a lesser extent) that of the bundle of the His-Purkinje system and the ventricles. Toxic effects result from delay in conduction and depression of myocardial contractility, leading to cardiac dysrhythmia and cardiogenic shock. Its oral use is limited immunological adverse effects such as systemic lupus erythematosus in patients on chronic oral therapy. Summary of clinical effects: Cardiovascular System: Sinus or atrial tachycardias, atrioventricular and intraventricular block hypotension, cardiogenic shock, torsades de pointes and ventricular fibrillation. Central Nervous System: Lethargy, coma, respiratory arrest may result Gastrointestinal Tract: Nausea, vomiting, diarrhea and abdominal pain have been reported. Others: Anticholinergic effects, hypokalemia, metabolic acidosis and pulmonary edema. Indications: Suppression of ventricular arrhythmias. Treatment of automatic and reentrant supraventricular tachycardia. Supraventricular arrhythmias: Like quinidine, procainamide is only moderately effective in converting atrial flutter or chronic atrial fibrillation to sinus rhythm. The drug can be used to prevent recurrences of atrial flutter or atrial fibrillation after cardioversion. Procainamide is indicated in the treatment of ventricular premature contractions, and in preventing recurrence of ventricular tachycardia after conversion to sinus rhythm by intravenous drugs or by electrical cardioversion or by other antiarrhythmic therapy; also in preventing recurrence of paroxysmal supraventricular tachycardia, atrial fibrillation or flutter following conversion to sinus rhythm by initial vagotonic maneuvers, digitalis preparations, other pharmaceutical antiarrhythmic agents, or electrical cardioversion. The drug is useful in patients with severe ventricular arrhythmias who do not respond to lidocaine. Procainamide is useful for acute terminations of arrhythmias associated with the Wolff-Parkinson-White Syndrome. Procainamide is used in the treatment of cardiac arrhythmias occurring in patients during general anesthesia. The drug has been used in conjunction with hexamethonium bromide to produce controlled hypotension and, consequently, ischemia of sufficient degree for relatively bloodless field surgery. The injection of procainamide into painful soft tissues in fibrosis and radiculitis and into the periarticular tissues in degenerative arthritis provided relief for considerable periods. Contraindications: Complete heart block: because of its effects in suppressing nodal or ventricular pacemakers. Torsades de Pointes: administration of procainamide in such case may aggravate this special type of ventricular extrasystole or tachycardia instead of suppressing it. Idiosyncratic hypersensitivity: in patients sensitive to procaine or other ester-type local anesthetics, cross sensitivity to procainamide is unlikely. However, a previous allergic reaction to procainamide is a contraindication. Lupus erythematosus: aggravation of symptoms is highly likely. Precautions: Preferably, procainamide should not be used in patients with bronchial asthma or myasthenia gravis. Accumulation of the drug may occur in patients with heart, renal or liver failure. Procainamide may enhance the effects of antihypertensive agents, propranolol, and some skeletal muscle relaxants. Grave hypotension may follow intravenous administration of procainamide; it should be injected slowly under monitoring of blood pressure and ECG. Although procainamide has been used effectively in the treatment of ventricular dysrhythmias caused by digitalis intoxication, its effects are unpredictable and fatalities have occurred. Procainamide should not be administered to nursing mothers. Routes of entry: Oral: Oral route is a common route of entry in cases of poisoning. Parenteral: Toxicity reactions can occur after intravenous injections. Absorption by route of exposure: Oral: Procainamide is almost completely and rapidly absorbed from the gastrointestinal tract. Peak levels are reached within 1 hr after ingestion of capsules, but somewhat later after administration of tablets. The bioavailability is approximately 85%. An overdose may significantly delay intestinal procainamide absorption and prolong poisoning symptoms. With the sustained-release formulations, bioavailability is decreased and the absorption is delayed. The duration of action exceeds 8 hours. Intramuscular: Plasma concentrations showed very large variations. Procainamide appears in the plasma within two minutes and peak concentrations are reached within 25 minutes. Intravenous: Procainamide acts almost immediately, the plasma level declines 10 to 15% hourly. Distribution by route of exposure: About 20% of the procainamide in plasma is bound to proteins. Procainamide is rapidly distributed into most body tissues except the brain. In patients with cardiac failure or shock the volume of distribution may decrease. Procainamide crosses the placental barrier and has been reported to accumulate in the fetus. Biological half-life by route of exposure: Peak plasma levels: Oral: one to 2 hours after ingestion. Intramuscular: eighty minutes after administration. Intravenous: Within several minutes. The plasma half life after therapeutic doses is 3 to 4 hours. However, in one patient the overdose plasma half life was 8.8 hours. Congestive heart failure increases the plasma procainamide half life to 5 to 8 hours. The half-life is reduced in children and is prolonged in patients with renal insufficiency. Its major active metabolite, N-acetylprocainamide (NAPA), has a longer half-life than procainamide, from 6 hours up to 36 hours in overdoses. Metabolism: The major metabolic pathway of procainamide is hepatic N-acetylation. The rate of acetylation is determined genetically and shows a bimodal distribution into slow and fast acetylators. The major active metabolite, NAPA, has antiarrhythmic properties. Other urinary metabolites include desethyl-NAPA and desethyl-procainamide, which account for 8 to 15% of a dose of procainamide. The exact relationship between antiarrhythmic activity and plasma levels of NAPA has not been established. Up to 15% of the intravenous procainamide therapeutic dose is metabolized to NAPA, and 81% of the NAPA dose is excreted unchanged in urine. In fast acetylators or in renal insufficiency, 40% or more of a dose of procainamide may be excreted as NAPA, and its concentrations in plasma may equal or exceed those of the parent drug. Procainamide hydrochloride is only slightly hydrolyzed by plasma enzymes (to p-amino benzoic acid and diethylaminoethylamine). Elimination by route of exposure: Procainamide is excreted in the urine with about 50% as unchanged procainamide, and up to about 30% as NAPA (less in slow acetylators). Since the elimination of both the parent drug and metabolites is almost entirely by renal excretion, they can accumulate to dangerous levels when renal failure or congestive heart failure is present. After an overdose, hepatic biotransformation probably is a more important elimination pathway than renal excretion. Following an overdose, the elimination half-life (in the presence of a serum creatinine of 5.8 mg/dL) of NAPA increased from 6 to 35.9 hours while the procainamide elimination increased from 3 to 10.5 hours. Mode of action: Toxicodynamics: Toxic effects result from quinidine-like effect with delay of conduction and depression of myocardial contractility. Contractility of the undamaged heart is usually not affected by therapeutic concentrations, although slight reduction of cardiac output may occur, and may be significant in the presence of myocardial damage. High toxic concentrations may prolong atrioventricular conduction time or induce atrioventricular block or even cause abnormal automaticity and spontaneous firing, by unknown mechanisms. The toxic mechanism of the drug is dose dependent and is related to depression of contractility, decreased vascular resistance secondary to direct vasodilatation and some alpha adrenergic blocking. Besides the cardiovascular effects, procainamide produces CNS depression and has anticholinergic effects. Pharmacodynamics: Procainamide is an antiarrhythmic agent with electrophysiological properties similar to that of quinidine. Procainamide increases the effective refractory period of the atria, of the bundle of His-Purkinje system and of the ventricles. It reduces impulse conduction velocity in atria, His-Purkinje fibers, and ventricular muscle. But it has also variable effects on the atrioventricular node, a direct slowing action and a weaker vagolytic effect which may speed atrio-conduction slightly. Myocardial excitability is reduced in the atria, Purkinje fibers, papillary muscles, and ventricles by an increase in the threshold for excitation. NAPA is less potent than procainamide, and some of its cardiac actions are qualitatively different. Procainamide does not produce alpha-adrenergic blockade, but, in the dog, it can block autonomic ganglia weakly and cause a measurable impairment of cardiovascular reflexes. Human data: Adults: A single oral dose may produce symptoms of toxicity. Ingestion of 3 gm may be dangerous, especially if patient is slow acetylator or has renal impairment or underlying heart disease. Death was reported from intravenous administration. Interactions: If other antiarrhythmic drugs are being used, additive effects on the heart may occur with procainamide administration, and dosage reduction may be necessary. Anticholinergic drugs administered concurrently with procainamide may produce additive antivagal effects on A-V nodal conduction. Patients taking procainamide who require neuromuscular blocking agents such as succinylcholine may require less than usual doses of the latter, due to procainamide effect on reducing acetylcholine release. The neuromuscular blocking activity of an antibiotic having such action may be accentuated by procainamide. The hypotensive action of antihypertensive agents, including thiazide diuretics, may be potentiated by procainamide. Cimetidine therapy given to older male patients taking procainamide may increase steady-state concentrations of procainamide. Main adverse effects: The side-effects most frequently reported after high dosage of procainamide include anorexia, diarrhea, nausea, and vomiting. Intravenous administration may cause hypotension, ventricular fibrillation or asystole if the injection is too rapid. Following chronic administration, systemic lupus erythematosus-like syndrome may develop. Other side effects which have been reported include mental depression, dizziness, psychosis with hallucinations, joint and muscle pain, muscular weakness, a bitter taste, flushing, skin rashes, pruritus, angioneurotic edema and hypersensitivity leading to chills, fever and urticaria. Leucopenia and agranulocytosis have followed repeated use of procainamide. Neutropenia, thrombocytopenia, or hemolytic anemia may rarely be encountered. High concentrations of procainamide in plasma can produce ventricular premature depolarization, ventricular tachycardia, or ventricular fibrillation. Hepatomegaly with increased serum aminotransferase level has been reported after a single oral dose. Mild hypovolemia, hypokalemia, metabolic acidosis may occur. Increased QT interval and prolonged QRS together with hypotension are sensitive indexes of serious poisoning. Parenteral administration of procainamide should be monitored electrocardiographically to give evidence of impending heart block. Acute poisoning: Ingestion: Serious toxic effects include conduction disturbances (QRS, QT prolongations), ventricular arrhythmias and cardiogenic shock. Increased ventricular extrasystoles, ventricular tachycardia (especially of the "torsades de pointes" type) or fibrillation may occur. The threshold of cardiac pacing is increased and the heart may even be nonresponsive. Lethargy, confusion and coma may occur. Other toxic manifestations are pulmonary edema, respiratory depression, urticaria, pruritus, nausea, vomiting, diarrhea and abdominal pain. Psychosis with hallucinations have been reported occasionally. Parenteral exposure: Intravenous administration may cause hypotension, ventricular fibrillation or asystole if the injection is too rapid. Chronic poisoning: Ingestion: A lupus erythematosus like syndrome of arthralgia, pleural or abdominal pain, and sometimes arthritis, pleural effusion, pericarditis, fever, chills, myalgia, and possibly related hematologic or skin lesions is fairly common after prolonged procainamide administration. Neutropenia, thrombocytopenia, or hemolytic anemia may rarely be encountered. Agranulocytosis has occurred after repeated use of procainamide. Course, prognosis, cause of death: Presence of PVCs and runs of ventricular tachycardia that are almost always successfully treated. Prognosis is usually good if there is not progress to ventricular fibrillation or asystole. Death is due to ventricular fibrillation or asystole. Long-term effects are agranulocytosis from hypersensitivity reaction, which is associated with 90% recovery rate. Systematic description of clinical effects: Cardiovascular: Acute: Sinus or atrial tachycardia due to the vagolytic effects. Conduction disturbances such as atrioventricular block, intraventricular block. Ventricular arrhythmias, including torsades de pointes, ventricular tachycardia and fibrillation. Hypotension and cardiogenic shock. ECG may show widening QRS, atrioventricular block, prolongation of QT interval and ventricular arrhythmia. Chronic: Chronic exposure may also produce arrhythmias. Cardiac tamponade due to pericarditis has been reported in a case of procainamide induced systemic lupus syndrome. Respiratory: Acute: Respiratory arrest and pulmonary edema. Neurological: Central nervous system (CNS): Acute: Dizziness or giddiness, weakness, mental depression, and psychosis with hallucinations have been reported occasionally. Lethargy may progress to coma. Skeletal and smooth muscle: Chronic: Skeletal muscular weakness and diaphragmatic paralysis has been reported in a case. Gastrointestinal: Acute: Anorexia, nausea, vomiting, abdominal pain, bitter taste, or diarrhea may occur in 3 to 4% of patients taking oral procainamide. Chronic: Nausea, vomiting may be seen. Hepatic: Acute: Hepatomegaly with increased serum aminotransferase level has been reported after a single oral dose. Dermatological: Chronic: Angioneurotic edema, urticaria, pruritus, flushing, and maculopapular rashes. Eye, ear, nose, throat: local effects: Acute: Blurred vision has been reported. Hematological: Chronic: Neutropenia, thrombocytopenia, or hemolytic anemia and agranulocytosis may rarely be encountered. Immunological: Chronic: Systemic lupus erythematosus like syndrome has been reported. Metabolic: Acid-base disturbances: Acute: Metabolic acidosis has been reported. Fluid and electrolyte disturbances: Acute: Hypokalemia may occur. Angioneurotic edema and maculopapular rashes have been reported. Special risks: Pregnancy: It is not known whether procainamide cause fetal harm when administered to a pregnant woman. Procainamide should be given to a pregnant woman only if clearly needed. Breast feeding: Both procainamide and NAPA are excreted in human milk. Therefore, procainamide should be given to a nursing mother only if clearly needed. Pediatric use: Safety and effectiveness in children have not been established. Plasma levels of NAPA may rise disproportionately in patients with renal impairment, because it is more dependent than procainamide on renal excretion for elimination. Elimination: Renal elimination of procainamide appears not to be affected by urinary pH or by urinary flow rate. However, because procainamide and NAPA are substantially eliminated by the kidney, it is important to maintain adequate renal functions.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 肝毒性

在临床试验中，普鲁卡因胺与血清转氨酶和碱性磷酸酶升高的低发生率有关。尽管普鲁卡因胺被广泛使用，但它很少与临床上明显的肝损伤病例有关联。在报告的病例中，发热和轻微症状通常在开始使用普鲁卡因胺（或重新开始使用）后1到3周内出现，与胆汁淤积性血清酶升高模式相关，伴或不伴有轻度黄疸（案例1）。免疫过敏特征通常存在（发热、皮疹、白细胞增多）。在报告的病例中，停用普鲁卡因胺后发热立即缓解，肝损伤的证据在几天到几周内消失。肝活检可能会显示除了轻度非特异性变化之外的肉芽肿。有趣的是，普鲁卡因胺的肝毒性非常类似于奎尼丁，但没有明显的对肝脏损伤的交叉敏感性。此外，长期使用普鲁卡因胺治疗的病人中，多达20%的患者会产生自身抗体，包括抗核抗体（ANA）和狼疮细胞（LE）阳性，其中一部分人会发展成“狼疮样”综合征。然而，这些自身免疫状况通常不伴随肝炎、血清酶升高或黄疸。

In clinical trials, procainamide was associated with a low rate of serum aminotransferase and alkaline phosphatase elevations. Despite wide scale use, procainamide has only rarely been linked to cases of clinically apparent liver injury. In reported cases, fever and mild symptoms arose within 1 to 3 weeks of starting (or within 1 day of restarting) procainamide, associated with a cholestatic pattern of serum enzyme elevations with mild or no jaundice (Case 1). Immunoallergic features were usually present (fever, rash, leukocytosis). In reported cases, fever resolved immediately and evidence of liver injury within a few days to weeks of stopping procainamide. Liver biopsy may how granulomas in addition to mild nonspecific changes. Interestingly, the hepatotoxicity of procainamide closely resembles that of quinidine, but there is no apparent cross sensitivity to the hepatic injury. In addition, up to 20% of patients on long term procainamide therapy develop autoantibodies, including ANA and LE prep positivity and a proportion develop a “lupus-like” syndrome. These autoimmune conditions, however, typically occur without an accompanying hepatitis, serum enzyme elevations or jaundice.

来源:LiverTox

毒理性

• 药物性肝损伤

化合物：普鲁卡因酰胺

Compound:procainamide

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

毒理性

• 药物性肝损伤

DILI 注解：较少的药物性肝损伤关注

DILI Annotation:Less-DILI-Concern

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

毒理性

• 药物性肝损伤

严重程度等级：4

Severity Grade:4

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

吸收、分配和排泄

• 吸收

75到95%

75 to 95%

来源:DrugBank

吸收、分配和排泄

• 消除途径

微量的物质可能以自由和结合的对氨基苯甲酸形式在尿液中排出，30%到60%以未改变的PA形式，以及6%到52%以NAPA衍生物形式。

Trace amounts may be excreted in the urine as free and conjugated p-aminobenzoic acid, 30 to 60 percent as unchanged PA, and 6 to 52 percent as the NAPA derivative.

来源:DrugBank

吸收、分配和排泄

• 分布容积

2 升/千克

2 L/kg

来源:DrugBank

吸收、分配和排泄

普鲁卡因酰胺在胃肠道中被迅速且几乎完全吸收。当口服给药时，其血药浓度在大约60分钟内达到最大值；静脉注射给药后，血药浓度峰值在15-60分钟内达到。

PROCAINAMIDE IS RAPIDLY & ALMOST COMPLETELY ABSORBED FROM GI TRACT. WHEN... GIVEN ORALLY, ITS PLASMA CONCN BECOMES MAX IN ABOUT 60 MIN; AFTER IM ADMIN PEAK PLASMA CONCN ARE REACHED IN 15-60 MIN.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在正常血浆浓度下，只有大约15%的药物与血浆中的大分子物质结合。除大脑外，大多数组织中药物的浓度高于血浆中的浓度。大约60%的药物通过肾脏排泄。2%到10%的药物以自由态和结合态的对氨基苯甲酸形式在尿液中回收。

AT ORDINARY PLASMA CONCN, ONLY 15%...IS BOUND TO MACROMOLECULAR CONSTITUENTS OF PLASMA. CONCN OF DRUG IN MOST TISSUES EXCEPT BRAIN IS GREATER THAN THAT IN PLASMA. APPROX 60% OF DRUG IS EXCRETED BY KIDNEY. TWO TO 10%...IS RECOVERED IN URINE AS FREE & CONJUGATED P-AMINOBENZOIC ACID.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 危险等级：
  6.1
• 海关编码：
  2924299090
• 储存条件：
  2-8°C

制备方法与用途

类别：有毒物品

毒性分级：中毒

急性毒性：

• 静脉注射 - 大鼠 LD50: 110 毫克/公斤
• 口服 - 小鼠 LD50: 525 毫克/公斤

可燃性危险特性：可燃；燃烧时产生有毒氮氧化物烟雾

储运特性：库房应通风、低温且干燥

灭火剂：干粉、泡沫、砂土、二氧化碳或雾状水

反应信息

• 作为反应物：
  描述：

  普鲁卡因胺 在 rhodium(III) chloride 、 tritium oxide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成
  参考文献：
  名称：

  均相三氯化铑催化剂对多种药物的区域特异性氘化和Tri化作用

  摘要：

  使用均相三氯化铑作为催化剂，已经研究了许多含有羧基，酰胺，芳烷基胺和苯胺官能团的药物的氘化和tri化作用。观察到氘的良好结合，并且对于大多数研究药物而言，邻位交换的区域特异性非常高。同样，在许多情况下，使用tri可以实现良好的结合（特定活性）和区域特异性。从本研究中包括的少量含杂环药物中也获得了令人满意的结果。

  DOI：

  10.1002/jps.2600800917
• 作为产物：
  描述：

  盐酸普鲁卡因胺 在 sodium hydroxide 作用下， 以 水 为溶剂， 生成 普鲁卡因胺
  参考文献：
  名称：

  Synthesis of Some Low Molecular Weight Derivatives of Procainamide

  摘要：

  AbstractLow molecular weight derivatives of procainamide, with a terminal functional group have been prepared. The synthesis and characterization of the succinic half‐amide respectively of N‐(ω‐amino alkanoyl)derivatives of the parent drug are reported.

  DOI：

  10.1002/bscb.19840930610
• 作为试剂：
  描述：

  、 N,N'-二琥珀酰亚胺基碳酸酯 、 三乙胺 、 苯甲酰胺 、 在 氮 、 四氢呋喃 、 二氯甲烷 、 Sodium sulfate-III 、 crude product 、 普鲁卡因胺 作用下， 以 四氢呋喃 为溶剂， 反应 18.0h， 以The purified protected procainamide analog, Formula 21, was isolated in an amount of 570 mg (60%)的产率得到普鲁卡因胺
  参考文献：
  名称：

  Synthesis and application of procainamide analogs for use in an immunoassay

  摘要：

  本发明涉及固定化普鲁卡因类似物，以及制备固定化普鲁卡因类似物的方法。这些固定化类似物是通过激活取代的对苯二甲酸衍生物上的羧基，使其向亲核攻击反应；将活化苯甲酸衍生物与多胺反应，以产生式3的苯甲酸衍生物；并将式3的苯甲酸衍生物与具有与脂肪族氨基反应的官能团的乳胶聚合物结合而制备的。还描述了使用固定化普鲁卡因类似物式3进行免疫测定的方法，包括制备含有所述固定化普鲁卡因类似物的溶液；向该溶液中加入怀疑含有普鲁卡因的样品；向该溶液中加入抗普鲁卡因抗体，并观察抗体添加后溶液浑浊度增加的速率。

  公开号：

  US07858399B2

文献信息

• [EN] IMIDAZOLIUM REAGENT FOR MASS SPECTROMETRY<br/>[FR] RÉACTIF D'IMIDAZOLIUM POUR SPECTROMÉTRIE DE MASSE
  申请人：HOFFMANN LA ROCHE

  公开号：WO2021234004A1

  公开（公告）日：2021-11-25

  The present invention relates to compounds which are suitable to be used in mass spectrometry as well as methods of mass spectrometric determination of analyte molecules using said compounds.

  本发明涉及适用于质谱的化合物，以及利用该化合物进行分析物分子的质谱测定方法。
• Phenanthrene derivatives for use as medicaments
  申请人：Valentia Biopharma

  公开号：EP2742974A1

  公开（公告）日：2014-06-18

  Phenanthrene derivatives of formula I for use as medicaments. The present invention refers to phenanthrene derivatives for use as medicaments, mainly in the prevention and/or treatment of DM1, HDL2, SCA8, DM2, SCA3, FXTAS, FTD/ALS, and SCA31. In a preferred embodiment, phenanthrene derivatives of the invention are also used as antimyotonic agents.

  公式I的菲南三烯衍生物用作药物。本发明涉及用作药物的菲南三烯衍生物，主要用于预防和/或治疗DM1、HDL2、SCA8、DM2、SCA3、FXTAS、FTD/ALS和SCA31。在一个优选实施例中，本发明的菲南三烯衍生物也用作抗肌肉张力剂。
• [EN] THERAPEUTIC ACRYLATES AS ENHANCED MEDICAL ADHESIVES<br/>[FR] ACRYLATES THÉRAPEUTIQUES UTILES EN TANT QU'ADHÉSIFS MÉDICAUX AMÉLIORÉS
  申请人：UNIV CARNEGIE MELLON

  公开号：WO2018052936A1

  公开（公告）日：2018-03-22

  Provided herein are therapeutic acrylate compounds useful as medical adhesives, comprising a therapeutic agent covalently linked to a methacrylate or cyanoacrylate moiety. Adhesive compositions and kits, such as liquid sutures and bone cement also are provided along with uses for the compositions.

  本文提供了作为医用粘合剂有用的治疗丙烯酸酯化合物，包括与甲基丙烯酸酯或氰丙烯酸酯基团共价连接的治疗剂。此外还提供了粘合剂组合物和套件，如液体缝合线和骨水泥，以及这些组合物的用途。
• Novel Thiazole Inhibitors of Fructose 1,6-Bishosphatase
  申请人：Dang Qun

  公开号：US20070225259A1

  公开（公告）日：2007-09-27

  Compounds of Formula I, their prodrugs and salts, their preparation and their uses are described.

  公式I的化合物，它们的前药和盐，它们的制备以及它们的用途被描述了。
• Substituted sulfonamidobenzamides, antiarrhythmic agents and
  申请人：Schering A.G.

  公开号：US04544654A1

  公开（公告）日：1985-10-01

  Novel substituted sulfonamidobenzamides are described as useful antiarrhythmic agents. Their use in the treatment of cardiac arrhythmias, especially re-entrant arrhythmias, via the prolongation of the action potential of cardiac tissue is provided. Pharmaceutical formulations containing such compounds are also disclosed.

  小说替代磺胺基苯甲酰胺被描述为有用的抗心律失常药物。通过延长心脏组织的动作电位来治疗心律失常，特别是再入性心律失常。还公开了含有这些化合物的药物配方。

表征谱图