U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

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
Structure of PROCAINAMIDE

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)

HIDE SMILES / InChI

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.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
PROCAINAMIDE HYDROCHLORIDE

Approved Use

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. 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 Date

508550400000
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
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

AUC

ValueDoseCo-administeredAnalytePopulation
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

Doses

DosePopulationAdverse events​
4100 mg steady, oral
MTD
Dose: 4100 mg
Route: oral
Route: steady
Dose: 4100 mg
Sources:
unhealthy, 25-79
Health Status: unhealthy
Age Group: 25-79
Sex: M+F
Sources:
Disc. AE: Nausea, Vomiting...
AEs leading to
discontinuation/dose reduction:
Nausea
Vomiting
Insomnia
Epigastric pain
Sources:
1 g single, intravenous
Recommended
unhealthy
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%)
Neutropenia (0.5%)
Hypoplastic anemia (0.5%)
Thrombocytopenia (0.5%)
Sources:
AEs

AEs

AESignificanceDosePopulation
Epigastric pain Disc. AE
4100 mg steady, oral
MTD
Dose: 4100 mg
Route: oral
Route: steady
Dose: 4100 mg
Sources:
unhealthy, 25-79
Health Status: unhealthy
Age Group: 25-79
Sex: M+F
Sources:
Insomnia Disc. AE
4100 mg steady, oral
MTD
Dose: 4100 mg
Route: oral
Route: steady
Dose: 4100 mg
Sources:
unhealthy, 25-79
Health Status: unhealthy
Age Group: 25-79
Sex: M+F
Sources:
Nausea Disc. AE
4100 mg steady, oral
MTD
Dose: 4100 mg
Route: oral
Route: steady
Dose: 4100 mg
Sources:
unhealthy, 25-79
Health Status: unhealthy
Age Group: 25-79
Sex: M+F
Sources:
Vomiting Disc. AE
4100 mg steady, oral
MTD
Dose: 4100 mg
Route: oral
Route: steady
Dose: 4100 mg
Sources:
unhealthy, 25-79
Health Status: unhealthy
Age Group: 25-79
Sex: M+F
Sources:
Bone marrow depression 0.5%
1 g single, intravenous
Recommended
unhealthy
Hypoplastic anemia 0.5%
1 g single, intravenous
Recommended
unhealthy
Neutropenia 0.5%
1 g single, intravenous
Recommended
unhealthy
Thrombocytopenia 0.5%
1 g single, intravenous
Recommended
unhealthy
Agranulocytosis grade 4, 0.5%
Disc. AE
1 g single, intravenous
Recommended
unhealthy
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG


OverviewOther

Drug as perpetrator​Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical 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

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
[Drug allergy among patients suffering from nasal polyps].
2001
[The value of transesophageal echocardiography for determination of tactics of cardioversion of atrial fibrillation].
2002
Effects of a typical I(Kr) channel blocker sematilide on the relationship between ventricular repolarization, refractoriness and onset of torsades de pointes.
2002 Apr
Herbal remedies: drug-herb interactions.
2002 Apr
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
On the diversity of oxidative bioactivation reactions on nitrogen-containing xenobiotics.
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
Effects of procainamide on transmural ventricular repolarisation.
2002 Jul
Atrial fibrillation: a new explanation of the old phenomenon.
2002 Jul
cDNA cloning, functional characterization, and tissue distribution of an alternatively spliced variant of organic cation transporter hOCT2 predominantly expressed in the human kidney.
2002 Jul
Quantification of pilsicainide in serum by capillary electrophoresis.
2002 Jul 20
Improvement of Drosophila acetylcholinesterase stability by elimination of a free cysteine.
2002 Jul 30
Stacking for nonaqueous capillary electrophoresis.
2002 Jun
Intrapericardial therapeutics: a pharmacodynamic and pharmacokinetic comparison between pericardial and intravenous procainamide delivery.
2002 Jun
The case of the slandered Halloween cupcake: survival after massive pediatric procainamide overdose.
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
Mechanism of action for N-substituted benzamide-induced apoptosis.
2002 Mar 18
Isoniazid-induced lupus erythematosus presenting with cardiac tamponade.
2002 Mar-Apr
Demethylation of ITGAL (CD11a) regulatory sequences in systemic lupus erythematosus.
2002 May
Reduction of cisplatin hepatotoxicity by procainamide hydrochloride in rats.
2002 May 10
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
Maintaining stability of sinus rhythm in atrial fibrillation: antiarrhythmic drugs versus ablation.
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
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
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.
Route of Administration: Other
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 Sat Jun 26 04:18:45 UTC 2021
Edited
by admin
on Sat Jun 26 04:18:45 UTC 2021
Record UNII
L39WTC366D
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
PROCAINAMIDE
HSDB   INN   VANDF   WHO-DD  
INN  
Official Name English
PROCAINAMIDE [HSDB]
Common Name English
NOVOCAINAMIDE
Common Name English
4-AMINO-N-(2-DIETHYLAMINOETHYL) BENZAMIDE
Common Name English
NSC-27461
Code English
SP 100 (PHARMACEUTICAL)
Common Name English
PROCAINAMIDE [VANDF]
Common Name English
PROCAINAMIDE [INN]
Common Name English
PROCAINAMIDE [WHO-DD]
Common Name English
N-(2-(DIETHYLAMINO)ETHYL)-4-AMINOBENZAMIDE
Systematic Name English
BENZAMIDE, 4-AMINO-N-(2-(DIETHYLAMINO)ETHYL)-
Systematic Name English
Classification Tree Code System Code
NDF-RT N0000175426
Created by admin on Sat Jun 26 04:18:45 UTC 2021 , Edited by admin on Sat Jun 26 04:18:45 UTC 2021
LIVERTOX 800
Created by admin on Sat Jun 26 04:18:45 UTC 2021 , Edited by admin on Sat Jun 26 04:18:45 UTC 2021
NCI_THESAURUS C93038
Created by admin on Sat Jun 26 04:18:45 UTC 2021 , Edited by admin on Sat Jun 26 04:18:45 UTC 2021
WHO-VATC QC01BA02
Created by admin on Sat Jun 26 04:18:45 UTC 2021 , Edited by admin on Sat Jun 26 04:18:45 UTC 2021
WHO-ATC C01BA02
Created by admin on Sat Jun 26 04:18:45 UTC 2021 , Edited by admin on Sat Jun 26 04:18:45 UTC 2021
NCI_THESAURUS C47793
Created by admin on Sat Jun 26 04:18:45 UTC 2021 , Edited by admin on Sat Jun 26 04:18:45 UTC 2021
Code System Code Type Description
MESH
D011342
Created by admin on Sat Jun 26 04:18:45 UTC 2021 , Edited by admin on Sat Jun 26 04:18:45 UTC 2021
PRIMARY
HSDB
3170
Created by admin on Sat Jun 26 04:18:45 UTC 2021 , Edited by admin on Sat Jun 26 04:18:45 UTC 2021
PRIMARY
IUPHAR
4811
Created by admin on Sat Jun 26 04:18:45 UTC 2021 , Edited by admin on Sat Jun 26 04:18:45 UTC 2021
PRIMARY
CAS
51-06-9
Created by admin on Sat Jun 26 04:18:45 UTC 2021 , Edited by admin on Sat Jun 26 04:18:45 UTC 2021
PRIMARY
ECHA (EC/EINECS)
200-078-8
Created by admin on Sat Jun 26 04:18:45 UTC 2021 , Edited by admin on Sat Jun 26 04:18:45 UTC 2021
PRIMARY
LACTMED
Procainamide
Created by admin on Sat Jun 26 04:18:45 UTC 2021 , Edited by admin on Sat Jun 26 04:18:45 UTC 2021
PRIMARY
ChEMBL
CHEMBL640
Created by admin on Sat Jun 26 04:18:45 UTC 2021 , Edited by admin on Sat Jun 26 04:18:45 UTC 2021
PRIMARY
DRUG BANK
DB01035
Created by admin on Sat Jun 26 04:18:45 UTC 2021 , Edited by admin on Sat Jun 26 04:18:45 UTC 2021
PRIMARY
FDA UNII
L39WTC366D
Created by admin on Sat Jun 26 04:18:45 UTC 2021 , Edited by admin on Sat Jun 26 04:18:45 UTC 2021
PRIMARY
PUBCHEM
4913
Created by admin on Sat Jun 26 04:18:45 UTC 2021 , Edited by admin on Sat Jun 26 04:18:45 UTC 2021
PRIMARY
EPA CompTox
51-06-9
Created by admin on Sat Jun 26 04:18:45 UTC 2021 , Edited by admin on Sat Jun 26 04:18:45 UTC 2021
PRIMARY
NCI_THESAURUS
C61905
Created by admin on Sat Jun 26 04:18:45 UTC 2021 , Edited by admin on Sat Jun 26 04:18:45 UTC 2021
PRIMARY
RXCUI
8700
Created by admin on Sat Jun 26 04:18:45 UTC 2021 , Edited by admin on Sat Jun 26 04:18:45 UTC 2021
PRIMARY RxNorm
DRUG CENTRAL
2270
Created by admin on Sat Jun 26 04:18:45 UTC 2021 , Edited by admin on Sat Jun 26 04:18:45 UTC 2021
PRIMARY
WIKIPEDIA
PROCAINAMIDE
Created by admin on Sat Jun 26 04:18:45 UTC 2021 , Edited by admin on Sat Jun 26 04:18:45 UTC 2021
PRIMARY
INN
4179
Created by admin on Sat Jun 26 04:18:45 UTC 2021 , Edited by admin on Sat Jun 26 04:18:45 UTC 2021
PRIMARY
EVMPD
SUB10055MIG
Created by admin on Sat Jun 26 04:18:45 UTC 2021 , Edited by admin on Sat Jun 26 04:18:45 UTC 2021
PRIMARY
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