Details
Stereochemistry | ACHIRAL |
Molecular Formula | C13H21N3O |
Molecular Weight | 235.3258 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CCN(CC)CCNC(=O)c1ccc(cc1)N
InChI
InChIKey=REQCZEXYDRLIBE-UHFFFAOYSA-N
InChI=1S/C13H21N3O/c1-3-16(4-2)10-9-15-13(17)11-5-7-12(14)8-6-11/h5-8H,3-4,9-10,14H2,1-2H3,(H,15,17)
Molecular Formula | C13H21N3O |
Molecular Weight | 235.3258 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
Procainamide is a derivative of procaine with less CNS action. Procainamide hydrochloride injection is indicated for the treatment of documented ventricular arrhythmias, such as sustained ventricular tachycardia, that, in the judgement of the physician, are life threatening. Because of the proarrhythmic effects of procainamide, its use with lesser arrhythmias is generally not recommended. Treatment of patients with asymptomatic ventricular premature contractions should be avoided. Procainamide (PA) increases the effective refractory period of the atria, and to a lesser extent the bundle of His-Purkinje system and ventricles of the heart. It reduces impulse conduction velocity in the atria, His-Purkinje fibers, and ventricular muscle, but has variable effects on the atrioventricular (A-V) node, a direct slowing action and a weaker vagolytic effect, which may speed A-V conduction slightly. Myocardial excitability is reduced in the atria, Purkinje fibers, papillary muscles, and ventricles by an increase in the threshold for excitation, combined with inhibition of ectopic pacemaker activity by retardation of the slow phase of diastolic depolarization, thus decreasing automaticity especially in ectopic sites. 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. Therapeutic levels of PA may exert vagolytic effects and produce slight acceleration of heart rate, while high or toxic concentrations may prolong A-V conduction time or induce A-V block, or even cause abnormal automaticity and spontaneous firing by unknown mechanisms. Procainamide is sodium channel blocker. It stabilizes the neuronal membrane by inhibiting the ionic fluxes required for the initiation and conduction of impulses thereby effecting local anesthetic action.
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL2331043 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21917337 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | PROCAINAMIDE HYDROCHLORIDE Approved UseProcainamide hydrochloride injection is indicated for the treatment of documented ventricular arrhythmias, such as sustained ventricular tachycardia, that, in the judgement of the physician, are life-threatening. Because of the proarrhythmic effects of procainamide, its use with lesser arrhythmias is generally not recommended. Treatment of patients with asymptomatic ventricular premature contractions should be avoided. Initiation of procainamide treatment, as with other antiarrhythmic agents used to treat life-threatening arrhythmias, should be carried out in the hospital. Antiarrhythmic drugs have not been shown to enhance survival in patients with ventricular arrhythmias. Launch Date5.08550414E11 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
0.514 μg/mL |
1000 mg single, oral dose: 1000 mg route of administration: Oral experiment type: SINGLE co-administered: |
ACECAINIDE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
0.581 μg/mL |
1000 mg single, oral dose: 1000 mg route of administration: Oral experiment type: SINGLE co-administered: |
ACECAINIDE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
1.211 μg/mL |
1000 mg single, oral dose: 1000 mg route of administration: Oral experiment type: SINGLE co-administered: |
PROCAINAMIDE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
1.303 μg/mL |
1000 mg single, oral dose: 1000 mg route of administration: Oral experiment type: SINGLE co-administered: |
PROCAINAMIDE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
15.165 μg × h/mL |
1000 mg single, oral dose: 1000 mg route of administration: Oral experiment type: SINGLE co-administered: |
ACECAINIDE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
15.897 μg × h/mL |
1000 mg single, oral dose: 1000 mg route of administration: Oral experiment type: SINGLE co-administered: |
ACECAINIDE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
18.22 μg × h/mL |
1000 mg single, oral dose: 1000 mg route of administration: Oral experiment type: SINGLE co-administered: |
PROCAINAMIDE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
18.34 μg × h/mL |
1000 mg single, oral dose: 1000 mg route of administration: Oral experiment type: SINGLE co-administered: |
PROCAINAMIDE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
Doses
Dose | Population | Adverse events |
---|---|---|
4100 mg steady, oral MTD Dose: 4100 mg Route: oral Route: steady Dose: 4100 mg Sources: Page: p.85 |
unhealthy, 25-79 n = 19 Health Status: unhealthy Condition: ventricular arrhythmias Age Group: 25-79 Sex: M+F Population Size: 19 Sources: Page: p.85 |
Disc. AE: Nausea, Vomiting... AEs leading to discontinuation/dose reduction: Nausea Sources: Page: p.85Vomiting Insomnia Epigastric pain |
1 g single, intravenous Recommended Dose: 1 g Route: intravenous Route: single Dose: 1 g Sources: |
unhealthy Health Status: unhealthy Condition: ventricular arrhythmias Sources: |
Disc. AE: Agranulocytosis... Other AEs: Bone marrow depression, Neutropenia... AEs leading to discontinuation/dose reduction: Agranulocytosis (grade 4, 0.5%) Other AEs:Bone marrow depression (0.5%) Sources: Neutropenia (0.5%) Hypoplastic anemia (0.5%) Thrombocytopenia (0.5%) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Epigastric pain | Disc. AE | 4100 mg steady, oral MTD Dose: 4100 mg Route: oral Route: steady Dose: 4100 mg Sources: Page: p.85 |
unhealthy, 25-79 n = 19 Health Status: unhealthy Condition: ventricular arrhythmias Age Group: 25-79 Sex: M+F Population Size: 19 Sources: Page: p.85 |
Insomnia | Disc. AE | 4100 mg steady, oral MTD Dose: 4100 mg Route: oral Route: steady Dose: 4100 mg Sources: Page: p.85 |
unhealthy, 25-79 n = 19 Health Status: unhealthy Condition: ventricular arrhythmias Age Group: 25-79 Sex: M+F Population Size: 19 Sources: Page: p.85 |
Nausea | Disc. AE | 4100 mg steady, oral MTD Dose: 4100 mg Route: oral Route: steady Dose: 4100 mg Sources: Page: p.85 |
unhealthy, 25-79 n = 19 Health Status: unhealthy Condition: ventricular arrhythmias Age Group: 25-79 Sex: M+F Population Size: 19 Sources: Page: p.85 |
Vomiting | Disc. AE | 4100 mg steady, oral MTD Dose: 4100 mg Route: oral Route: steady Dose: 4100 mg Sources: Page: p.85 |
unhealthy, 25-79 n = 19 Health Status: unhealthy Condition: ventricular arrhythmias Age Group: 25-79 Sex: M+F Population Size: 19 Sources: Page: p.85 |
Bone marrow depression | 0.5% | 1 g single, intravenous Recommended Dose: 1 g Route: intravenous Route: single Dose: 1 g Sources: |
unhealthy Health Status: unhealthy Condition: ventricular arrhythmias Sources: |
Hypoplastic anemia | 0.5% | 1 g single, intravenous Recommended Dose: 1 g Route: intravenous Route: single Dose: 1 g Sources: |
unhealthy Health Status: unhealthy Condition: ventricular arrhythmias Sources: |
Neutropenia | 0.5% | 1 g single, intravenous Recommended Dose: 1 g Route: intravenous Route: single Dose: 1 g Sources: |
unhealthy Health Status: unhealthy Condition: ventricular arrhythmias Sources: |
Thrombocytopenia | 0.5% | 1 g single, intravenous Recommended Dose: 1 g Route: intravenous Route: single Dose: 1 g Sources: |
unhealthy Health Status: unhealthy Condition: ventricular arrhythmias Sources: |
Agranulocytosis | grade 4, 0.5% Disc. AE |
1 g single, intravenous Recommended Dose: 1 g Route: intravenous Route: single Dose: 1 g Sources: |
unhealthy Health Status: unhealthy Condition: ventricular arrhythmias Sources: |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
weak [IC50 <1000 uM] | ||||
yes [IC50 51.3 uM] | ||||
yes [Ki 178.1 uM] | ||||
yes [Ki 217 uM] | ||||
yes [Ki 50 uM] | ||||
yes [Ki 738 uM] |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
yes [Km 1280 uM] | yes (co-administration study) Comment: MATE1-HEK293 cells (5.0 mcM procainamide), Uptake = 47.6 mcL/mg protein/15 min, Vmax = 7.56 nmol/mg protein/2 min; Coadministration of Cimetidine (300 mg QID 3 Days & 1 hr before/5 hr after Procainamide on Day 4) increased Procainamide (500 mg QD on Day 4)/N-acetylprocaineamide AUC by 40%, 26% and N-acetylprocainamide Cmax by 33%. |
|||
yes [Km 1580 uM] | yes (co-administration study) Comment: MATE2-K-HEK293 cells (5.0 mcM procainamide), Uptake = 26.5 mcL/mg protein/15 min, Vmax = 6.77 nmol/mg protein/2 min; Coadministration of Cimetidine (300 mg QID 3 Days & 1 hr before/5 hr after Procainamide on Day 4) increased Procainamide (500 mg QD on Day 4)/N-acetylprocaineamide AUC by 40%, 26% and N-acetylprocainamide Cmax by 33%. |
|||
yes | ||||
yes | ||||
yes | yes (co-administration study) Comment: OCT2-HEK293 cells, Active uptake = 114 pmo/mg protein; Coadministration of Cimetidine (300 mg QID 3 Days & 1 hr before/5 hr after Procainamide on Day 4) increased Procainamide (500 mg QD on Day 4)/N-acetylprocaineamide AUC by 40%, 26% and N-acetylprocainamide Cmax by 33%. |
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
PubMed
Title | Date | PubMed |
---|---|---|
Transesophageal pacemaker therapy in atrial flutter after procainamide pretreatment. | 1999 Sep |
|
Effects of procainamide on membrane properties of thalamic neurons. | 2001 |
|
A nondeletional mechanism for central T-cell tolerance. | 2001 |
|
[Cardiac arrhythmias in pregnancy]. | 2001 |
|
New electrocardiographic leads and the procainamide test for the detection of the Brugada sign in sudden unexplained death syndrome survivors and their relatives. | 2001 Dec |
|
Effect of procainamide on the postrepolarization refractoriness in cardiac muscle: evaluation using the block coupling interval in the artificial isthmus model in the canine right atrium. | 2001 Jul |
|
Transport of choline and its relationship to the expression of the organic cation transporters in a rat brain microvessel endothelial cell line (RBE4). | 2001 Jun 6 |
|
Role of K+ channels in N-acetylprocainamide-induced relaxation of bovine tracheal smooth muscle. | 2001 Mar 9 |
|
[Brugada syndrome]. | 2001 Nov |
|
[The value of transesophageal echocardiography for determination of tactics of cardioversion of atrial fibrillation]. | 2002 |
|
Herbal remedies: drug-herb interactions. | 2002 Apr |
|
Syncope with ST-segment abnormalities resembling Brugada syndrome due to reversible myocardial ischemia. | 2002 Aug |
|
Comparison of the in vivo electrophysiological and proarrhythmic effects of amiodarone with those of a selective class III drug, sematilide, using a canine chronic atrioventricular block model. | 2002 Aug |
|
Comparison of the effects of four antiarrhythmic treatments for familial ventricular arrhythmias in Boxers. | 2002 Aug 15 |
|
Functional characterization of mouse cation transporter mOCT2 compared with mOCT1. | 2002 Aug 23 |
|
Investigation of water mobility and diffusivity in hydrating micronized low-substituted hydroxypropyl cellulose, hydroxypropylmethyl cellulose, and hydroxypropyl cellulose matrix tablets by magnetic resonance imaging (MRI). | 2002 Dec |
|
The cation transporters rOCT1 and rOCT2 interact with bicarbonate but play only a minor role for amantadine uptake into rat renal proximal tubules. | 2002 Dec |
|
Clinical and molecular heterogeneity in the Brugada syndrome: a novel gene locus on chromosome 3. | 2002 Feb 12 |
|
Acute and chronic electrophysiologic changes surrounding radiofrequency lesions. | 2002 Jan |
|
Effects of procainamide on transmural ventricular repolarisation. | 2002 Jul |
|
Atrial fibrillation: a new explanation of the old phenomenon. | 2002 Jul |
|
Stacking for nonaqueous capillary electrophoresis. | 2002 Jun |
|
Pronounced effect of procainamide on clockwise right atrial isthmus conduction compared with counterclockwise conduction: possible mechanism of the greater incidence of common atrial flutter during antiarrhythmic therapy. | 2002 Mar |
|
Fever unmasking the Brugada syndrome. | 2002 Nov |
|
Atrial fibrillation in pregnancy associated with oral terbutaline. | 2002 Nov |
|
Anti-arrhythmic efficacy of nifekalant hydrochloride, a pure class III anti-arrhythmic agent, in patients with healed myocardial infarction and inducible sustained ventricular tachycardia. | 2002 Nov |
|
Diagnosing pericarditis. | 2002 Nov 1 |
|
Lack of association between arylamine N-acetyltransferase 2 (NAT2) polymorphism and systemic lupus erythematosus. | 2002 Oct |
|
Purification and characterization of acetylcholinesterase from cotton aphid (Aphis gossypii Glover). | 2002 Sep |
|
Fluoroquinolones in the elderly: safety considerations. | 2003 |
|
Procainamide and quinidine inhibition of the human hepatic degradation of meperidine in vitro. | 2003 Apr |
|
Cardiac arrhythmias in pregnancy: clinical and therapeutic considerations. | 2003 Apr |
|
A patient with chaotic atrial tachycardia. | 2003 Apr |
|
Solution and solid state properties of a set of procaine and procainamide derivatives. | 2003 Apr |
|
Ibutilide versus amiodarone in atrial fibrillation: a double-blinded, randomized study. | 2003 Apr |
|
Electrocardiographic manifestations: wide complex tachycardia due to accessory pathway. | 2003 Apr |
|
Amiodarone-induced systemic lupus erythematosus. | 2003 Feb |
|
Unusual case of antiphospholipid antibody syndrome presenting with extensive cutaneous infarcts in a patient on long-term procainamide therapy. | 2003 Feb |
|
Differential usage of IkappaBalpha and IkappaBbeta in regulation of apoptosis versus gene expression. | 2003 Jan 31 |
|
Reactive metabolites and adverse drug reactions: clinical considerations. | 2003 Jun |
|
Comparison of the effect of class IA antiarrhythmic drugs on transmembrane potassium currents in rabbit ventricular myocytes. | 2003 Mar |
|
Hydralazine may induce autoimmunity by inhibiting extracellular signal-regulated kinase pathway signaling. | 2003 Mar |
|
Atrial fibrillation after ondansetron for the prevention and treatment of postoperative nausea and vomiting: a case report. | 2003 Mar |
|
Left atrial size after cardioversion for atrial fibrillation: effect of external direct current shock. | 2003 Mar |
|
Inhaled nitric oxide modifies left ventricular diastolic stress in the presence of vasoactive agents in heart failure. | 2003 Mar 15 |
|
Evaluation of hydralazine and procainamide effects on fibroblast membrane fluidity. | 2003 May |
|
[Cardiac arrhythmias during pregnancy--what to do?]. | 2003 May |
|
Prediction of in vivo hepatic clearance from in vitro data using cryopreserved human hepatocytes. | 2003 May |
|
Reactivation of tumor suppressor genes by the cardiovascular drugs hydralazine and procainamide and their potential use in cancer therapy. | 2003 May |
|
Role of fibrillation cycle length in spontaneous and drug-induced termination of human atrial fibrillation. | 2003 May |
Patents
Sample Use Guides
For treatment of arrhythmias associated with anesthesia or surgical operation, the suggested dose is 100 to 500 mg by intramuscular injection.
intravenous dose: Initial Loading Infusion is 20 mg/mL in 50 mL
Route of Administration:
Other
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/10369326
Procainamide (PA) inhibited the degradation of both cocaine (COC) and cocaethylene (CE) when either was incubated in human liver homogenates for 3 h at 37 degrees C in the presence of PA concentrations: 42.5, 85, and 340 umol/L.
Substance Class |
Chemical
Created
by
admin
on
Edited
Sat Jun 26 04:18:45 UTC 2021
by
admin
on
Sat Jun 26 04:18:45 UTC 2021
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Record UNII |
L39WTC366D
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Record Status |
Validated (UNII)
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Record Version |
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NDF-RT |
N0000175426
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LIVERTOX |
800
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NCI_THESAURUS |
C93038
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WHO-VATC |
QC01BA02
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WHO-ATC |
C01BA02
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NCI_THESAURUS |
C47793
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200-078-8
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Procainamide
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CHEMBL640
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DB01035
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8700
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2270
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PROCAINAMIDE
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SUB10055MIG
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Related Record | Type | Details | ||
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TRANSPORTER -> INHIBITOR | |||
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TRANSPORTER -> INHIBITOR | |||
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TRANSPORTER -> INHIBITOR | |||
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TRANSPORTER -> INHIBITOR | |||
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TRANSPORTER -> SUBSTRATE |
Vmax
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TRANSPORTER -> SUBSTRATE |
Km
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TRANSPORTER -> SUBSTRATE |
Vmax
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SALT/SOLVATE -> PARENT | |||
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TRANSPORTER -> SUBSTRATE |
Km
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TRANSPORTER -> INHIBITOR | |||
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BINDER->LIGAND |
Related Record | Type | Details | ||
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METABOLITE -> PARENT |
Metabolite to parent drug ratio in non-uraemic human plasma.
METABOLITE TO PARENT DRUG RATIO
PLASMA; URINE
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METABOLITE -> PARENT |
Percent of dose excreted in urine as metabolite.
AMOUNT EXCRETED
URINE
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METABOLITE ACTIVE -> PARENT |
Related Record | Type | Details | ||
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ACTIVE MOIETY |