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

Details

Stereochemistry ACHIRAL
Molecular Formula C13H21N3O.ClH
Molecular Weight 271.786
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of PROCAINAMIDE HYDROCHLORIDE

SMILES

Cl.CCN(CC)CCNC(=O)C1=CC=C(N)C=C1

InChI

InChIKey=ABTXGJFUQRCPNH-UHFFFAOYSA-N
InChI=1S/C13H21N3O.ClH/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);1H

HIDE SMILES / InChI

Molecular Formula C13H21N3O
Molecular Weight 235.3253
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula ClH
Molecular Weight 36.461
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

1986
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: 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
Vomiting
Insomnia
Epigastric pain
Sources: Page: p.85
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: 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
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
[Procainamide-induced skin eruption associated with disseminated intravascular coagulation in a patient with sustained ventricular tachycardia].
1999 Sep 1
[Cardiac arrhythmias in pregnancy].
2001
Importance of QT interval determination and renal function assessment during antiarrhythmic drug therapy.
2001 Apr
Spectral characteristics of human atrial fibrillation waves of the right atrial free wall with respect to the duration of atrial fibrillation and effect of class I antiarrhythmic drugs.
2001 Dec
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
Reversal of GSTP1 CpG island hypermethylation and reactivation of pi-class glutathione S-transferase (GSTP1) expression in human prostate cancer cells by treatment with procainamide.
2001 Dec 15
Nerve control of type 2A MHC isoform expression in regenerating slow skeletal muscle.
2001 Jan
Intravenous antiarrhythmic agents.
2001 Jan
Pattern of inheritance in three sudden unexplained death syndrome ("Lai-tai") families.
2001 Jun
Moxifloxacin: clinical efficacy and safety.
2001 Mar 1
Mechanisms of antiarrhythmic drug action on termination of atrial flutter.
2001 May
Atrial fibrillation: prevalence after minimally invasive direct and standard coronary artery bypass.
2001 May
In vitro production of antibodies to histones in patients receiving chronic procainamide therapy.
2001 Sep
[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
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
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
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
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
Mechanism of action for N-substituted benzamide-induced apoptosis.
2002 Mar 18
Influence of midazolam on pharmacokinetic parameters of procainamide in rabbits.
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
Diagnosing pericarditis.
2002 Nov 1
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
Amiodarone-induced systemic lupus erythematosus.
2003 Feb
Reactive metabolites and adverse drug reactions: clinical considerations.
2003 Jun
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
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 Fri Dec 15 15:08:33 GMT 2023
Edited
by admin
on Fri Dec 15 15:08:33 GMT 2023
Record UNII
SI4064O0LX
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
PROCAINAMIDE HYDROCHLORIDE
EP   MART.   MI   ORANGE BOOK   USP   USP-RS   VANDF   WHO-DD   WHO-IP  
Common Name English
PROCAINAMIDE HYDROCHLORIDE [MART.]
Common Name English
PROCAINAMIDE HYDROCHLORIDE [EP MONOGRAPH]
Common Name English
PROCAN
Brand Name English
Procainamide hydrochloride [WHO-DD]
Common Name English
PROCAINAMIDE HYDROCHLORIDE [JAN]
Common Name English
PROCAINAMIDE HCL
Common Name English
BENZAMIDE, 4-AMINO-N-(2-(DIETHYLAMINO)ETHYL)-, MONOHYDROCHLORIDE
Common Name English
PRONESTYL
Brand Name English
PROCAPAN
Brand Name English
PROCAINAMIDI HYDROCHLORIDUM [WHO-IP LATIN]
Common Name English
PROCAINAMIDE HYDROCHLORIDE [VANDF]
Common Name English
PROCAINAMIDE HYDROCHLORIDE [USP MONOGRAPH]
Common Name English
CARDIORYTMIN
Common Name English
PROCAINAMIDE HYDROCHLORIDE [ORANGE BOOK]
Common Name English
4-AMINO-N-(2-(DIETHYLAMINO)ETHYL)BENZAMIDE MONOHYDROCHLORIDE [WHO-IP]
Systematic Name English
PROCAINAMIDE HYDROCHLORIDE [MI]
Common Name English
PROCAINAMIDE HYDROCHLORIDE [WHO-IP]
Common Name English
PROCAINAMIDE HYDROCHLORIDE [USP-RS]
Common Name English
PROCANBID
Brand Name English
NSC-757279
Code English
AMIDOPROCAINE
Common Name English
P-AMINO-N-(2-(DIETHYLAMINO)ETHY)BENZAMIDE MONOHYDROCHLORIDE
Common Name English
PROCAN SR
Brand Name English
Classification Tree Code System Code
NCI_THESAURUS C47793
Created by admin on Fri Dec 15 15:08:33 GMT 2023 , Edited by admin on Fri Dec 15 15:08:33 GMT 2023
NCI_THESAURUS C93038
Created by admin on Fri Dec 15 15:08:33 GMT 2023 , Edited by admin on Fri Dec 15 15:08:33 GMT 2023
Code System Code Type Description
EPA CompTox
DTXSID2049422
Created by admin on Fri Dec 15 15:08:33 GMT 2023 , Edited by admin on Fri Dec 15 15:08:33 GMT 2023
PRIMARY
NSC
757279
Created by admin on Fri Dec 15 15:08:33 GMT 2023 , Edited by admin on Fri Dec 15 15:08:33 GMT 2023
PRIMARY
WHO INTERNATIONAL PHARMACOPEIA
PROCAINAMIDE HYDROCHLORIDE
Created by admin on Fri Dec 15 15:08:33 GMT 2023 , Edited by admin on Fri Dec 15 15:08:33 GMT 2023
PRIMARY Description: A white to yellowish white, crystalline powder; odourless. Solubility: Very soluble in water; freely soluble in ethanol (~750 g/l) TS; very slightly soluble in ether R. Category: Antiarrhythmic. Storage: Procainamide hydrochloride should be kept in a tightly closed container, protected from light. Additional information: Procainamide hydrochloride is hygroscopic. Even in the absence of light, Procainamide hydrochloride is gradually degraded on exposure to a humid atmosphere, the decomposition being faster at higher temperatures. Definition: Procainamide hydrochloride contains not less than 98.0% and not more than 101.0% of C13H21N3O,HCl, calculated with reference to the dried substance.
SMS_ID
100000085081
Created by admin on Fri Dec 15 15:08:33 GMT 2023 , Edited by admin on Fri Dec 15 15:08:33 GMT 2023
PRIMARY
DAILYMED
SI4064O0LX
Created by admin on Fri Dec 15 15:08:33 GMT 2023 , Edited by admin on Fri Dec 15 15:08:33 GMT 2023
PRIMARY
PUBCHEM
66068
Created by admin on Fri Dec 15 15:08:33 GMT 2023 , Edited by admin on Fri Dec 15 15:08:33 GMT 2023
PRIMARY
RXCUI
155056
Created by admin on Fri Dec 15 15:08:33 GMT 2023 , Edited by admin on Fri Dec 15 15:08:33 GMT 2023
PRIMARY RxNorm
CHEBI
8429
Created by admin on Fri Dec 15 15:08:33 GMT 2023 , Edited by admin on Fri Dec 15 15:08:33 GMT 2023
PRIMARY
EVMPD
SUB04045MIG
Created by admin on Fri Dec 15 15:08:33 GMT 2023 , Edited by admin on Fri Dec 15 15:08:33 GMT 2023
PRIMARY
ChEMBL
CHEMBL640
Created by admin on Fri Dec 15 15:08:33 GMT 2023 , Edited by admin on Fri Dec 15 15:08:33 GMT 2023
PRIMARY
CAS
614-39-1
Created by admin on Fri Dec 15 15:08:33 GMT 2023 , Edited by admin on Fri Dec 15 15:08:33 GMT 2023
PRIMARY
DRUG BANK
DBSALT000724
Created by admin on Fri Dec 15 15:08:33 GMT 2023 , Edited by admin on Fri Dec 15 15:08:33 GMT 2023
PRIMARY
FDA UNII
SI4064O0LX
Created by admin on Fri Dec 15 15:08:33 GMT 2023 , Edited by admin on Fri Dec 15 15:08:33 GMT 2023
PRIMARY
ECHA (EC/EINECS)
210-381-7
Created by admin on Fri Dec 15 15:08:33 GMT 2023 , Edited by admin on Fri Dec 15 15:08:33 GMT 2023
PRIMARY
NCI_THESAURUS
C47687
Created by admin on Fri Dec 15 15:08:33 GMT 2023 , Edited by admin on Fri Dec 15 15:08:33 GMT 2023
PRIMARY
MERCK INDEX
m9144
Created by admin on Fri Dec 15 15:08:33 GMT 2023 , Edited by admin on Fri Dec 15 15:08:33 GMT 2023
PRIMARY Merck Index
RS_ITEM_NUM
1563502
Created by admin on Fri Dec 15 15:08:33 GMT 2023 , Edited by admin on Fri Dec 15 15:08:33 GMT 2023
PRIMARY
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