NAV

Ajmaline

Identification

Summary

Ajmalineis an antiarrhythmic used to manage a variety of forms of tachycardias.

Generic Name
Ajmaline
DrugBank Accession Number
DB01426
Background

An alkaloid found in the root of Rauwolfia serpentina, among other plant sources. It is a class Ia antiarrhythmic agent that apparently acts by changing the shape and threshold of cardiac action potentials. Ajmaline produces potent sodium channel blocking effects and a very short half-life which makes it a very useful drug for acute intravenous treatments. The drug has been very popular in some countries for the treatment of atrial fibrillation in patients with the Wolff–Parkinson–White syndrome and in well tolerated monomorphic ventricular tachycardias. It has also been used for many years as a drug to challenge the conduction system of the heart in cases of bundle branch block and syncope. In these cases, abnormal prolongation of the HV interval has been taken as a proof for infrahisian conduction defects tributary for permanent pacemaker implantation.

Type
Small Molecule
Groups
Approved, Experimental
Structure
 3D
Similar Structures
Weight
Average: 326.4326
Monoisotopic: 326.199428086
Chemical Formula
C20H26N2O2
Synonyms
  • (+)-Ajmaline
  • (5aR,6S,8S,10S,11S,11aS,12aR,13R)-5-methyl-5a,6,8,9,10,11,11a,12-octahydro-5H-6,10:11,12a-dimethanoindolo[3,2-b]quinolizine-8,13-diol
  • Ajmalin
  • Ajmaline

Pharmacology

Indication

For use as an antiarrhythmic agent.

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Associated Conditions
Associated Therapies
Contraindications & Blackbox Warnings
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Pharmacodynamics

Ajmaline is a class 1A antiarrhythmic agent. By interfering with the sodium channels, this drug allows for improvement in abnormal rhythms of the heart

Mechanism of action

The class I antiarrhythmic agents interfere with the sodium channel. A class IA agent lengthens the action potential (right shift) which brings about improvement in abnormal heart rhythms. This drug in particular has a high affinity for the Nav 1.5 sodium channel.

Target Actions Organism
ASodium channel protein type 5 subunit alpha
inhibitor
 Humans
Absorption

Not Available

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism
Not Available
Route of elimination

Not Available

Half-life

Not Available

Clearance

Not Available

Adverse Effects
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Toxicity

Not Available

Pathways
Not Available
Pharmacogenomic Effects/ADRsBrowse all" title="" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
Not Available

Interactions

Drug InteractionsLearn More" title="" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
这些信息不应该被解释the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction
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interactions in your software
Acebutolol Acebutolol may increase the arrhythmogenic activities of Ajmaline.
Acetyldigitoxin Acetyldigitoxin may increase the arrhythmogenic activities of Ajmaline.
Acrivastine The risk or severity of QTc prolongation can be increased when Ajmaline is combined with Acrivastine.
Adenosine Adenosine may increase the arrhythmogenic activities of Ajmaline.
Alfuzosin The risk or severity of QTc prolongation can be increased when Alfuzosin is combined with Ajmaline.
Alimemazine The risk or severity of QTc prolongation can be increased when Alimemazine is combined with Ajmaline.
Amantadine The risk or severity of QTc prolongation can be increased when Amantadine is combined with Ajmaline.
Amifampridine The risk or severity of QTc prolongation can be increased when Ajmaline is combined with Amifampridine.
Amiodarone Amiodarone may increase the QTc-prolonging activities of Ajmaline.
Amisulpride The risk or severity of QTc prolongation can be increased when Ajmaline is combined with Amisulpride.
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Food Interactions
Not Available

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International/Other Brands
Ajimalin

Categories

ATC Codes
C01BA05 — Ajmaline
Drug Categories
Chemical TaxonomyProvided byClassyfire
Description
This compound belongs to the class of organic compounds known as ajmaline-sarpagine alkaloids. These are organic compounds containing either of the ajmalan, sarpagan skeleton, or derivative thereof. The Sarpagine (Akuammidine) group, based on the sarpagan nucleus, arises from bond formation between C-16 and C-5 of the corynantheine precursor. Ajmaline alkaloids are based on a 17,19-secoyohimban skeleton (oxayohimban) which is invariably present as an ether.
Kingdom
Organic compounds
Super Class
Alkaloids and derivatives
Class
Ajmaline-sarpagine alkaloids
Sub Class
Not Available
Direct Parent
Ajmaline-sarpagine alkaloids
Alternative Parents
Beta carbolines/Quinolizidines/Quinuclidines/Dialkylarylamines/Azepanes/Aralkylamines/Piperidines/Benzenoids/二级醇/Hemiaminals
show 4 more
Substituents
Alcohol/Alkanolamine/Amine/Aralkylamine/Aromatic heteropolycyclic compound/Azacycle/Azepane/Benzenoid/Beta-carboline/Cyclic alcohol
show 18 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
hemiaminal, monoterpenoid indole alkaloid (CHEBI:28462)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
1PON08459R
CAS number
4360-12-7
InChI Key
CJDRUOGAGYHKKD-HEFSZTOGSA-N
InChI
InChI=1S/C20H26N2O2/c1-3-10-11-8-14-17-20(12-6-4-5-7-13(12)21(17)2)9-15(16(11)18(20)23)22(14)19(10)24/h4-7,10-11,14-19,23-24H,3,8-9H2,1-2H3/t10-,11-,14-,15-,16?,17-,18+,19+,20+/m0/s1
IUPAC Name
(1R,9R,10S,12R,13S,14R,16S,18R)-13-ethyl-8-methyl-8,15-diazahexacyclo[14.2.1.0^{1,9}.0^{2,7}.0^{10,15}.0^{12,17}]nonadeca-2,4,6-triene-14,18-diol
SMILES
[H][C@]12C[C@]34[C@H](O)C1[C@@]1([H])C[C@]([H])(N2[C@H](O)[C@H]1CC)[C@]3([H])N(C)C1=CC=CC=C41

References

Synthesis Reference

Ivan F. Makarevich, Yaroslav I. Khadzhai, Valeria V. Pavlova, Anastasia V. Nikolaeva, "Cardenolide and bufadienolide derivatives of ajmaline and process for producing same." U.S. Patent US4175078, issued May, 1975.

 US4175078
General References
  1. Brugada J, Brugada P, Brugada R: The ajmaline challenge in Brugada syndrome: a useful tool or misleading information? Eur Heart J. 2003 Jun;24(12):1085-6. [Article]
Human Metabolome Database
HMDB0015495
KEGG Drug
D00199
KEGG Compound
C06542
PubChem Compound
441080
PubChem Substance
46506449
ChemSpider
10145712
RxNav
423
ChEBI
28462
ChEMBL
CHEMBL2357792
PharmGKB
PA164776839
Wikipedia
Ajmaline

Clinical Trials

Clinical TrialsLearn More" title="" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count
4 Completed Treatment Atrial Fibrillation/Brugada Syndrome (BrS)/Ventricular Tachycardia (VT) 1
2 Unknown Status Diagnostic Brugada Syndrome (BrS)/Sudden Death 1
Not Available Completed Treatment Brugada Syndrome (BrS) 1
Not Available Recruiting Not Available Brugada Syndrome (BrS)/Cardiovascular Mortality/Channelopathies/Ventricular Fibrillation 1
Not Available Unknown Status Not Available Brugada Syndrome (BrS) 1

Pharmacoeconomics

制造商
Not Available
Packagers
Not Available
Dosage Forms
Form Route Strength
Injection, solution, concentrate Intravenous 5 mg/ml
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Property Value Source
melting point (°C) 206 °C PhysProp
water solubility 490 mg/L (at 30 °C) YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP 1.81 HANSCH,C ET AL. (1995)
logS -2.82 ADME Research, USCD
Predicted Properties
Property Value Source
Water Solubility 4.09 mg/mL ALOGPS
logP 1.72 ALOGPS
logP 1.85 Chemaxon
logS -1.9 ALOGPS
pKa (Strongest Acidic) 13.28 Chemaxon
pKa (Strongest Basic) 7.2 Chemaxon
Physiological Charge 1 Chemaxon
Hydrogen Acceptor Count 4 Chemaxon
Hydrogen Donor Count 2 Chemaxon
Polar Surface Area 46.94 Å2 Chemaxon
Rotatable Bond Count 1 Chemaxon
Refractivity 92.57 m3·mol-1 Chemaxon
Polarizability 36.73 Å3 Chemaxon
Number of Rings 6 Chemaxon
Bioavailability 1 Chemaxon
Rule of Five Yes Chemaxon
Ghose Filter Yes Chemaxon
Veber's Rule No Chemaxon
MDDR-like Rule No Chemaxon
Predicted ADMET Features
Property Value 概率
Human Intestinal Absorption + 0.9264
Blood Brain Barrier + 0.9273
Caco-2 permeable + 0.8867
P-glycoprotein substrate Substrate 0.6942
P-glycoprotein inhibitor I Inhibitor 0.7071
22抑制剂二世 Non-inhibitor 0.6439
Renal organic cation transporter Non-inhibitor 0.6752
CYP450 2C9 substrate Non-substrate 0.8249
CYP450 2D6 substrate Non-substrate 0.7415
CYP450 3A4 substrate Substrate 0.6739
CYP450 1A2 substrate Non-inhibitor 0.9045
CYP450 2C9 inhibitor Non-inhibitor 0.9071
CYP450 2D6 inhibitor Inhibitor 0.8932
CYP450 2C19 inhibitor Non-inhibitor 0.9025
CYP450 3A4 inhibitor Non-inhibitor 0.8309
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.5565
Ames test Non AMES toxic 0.6621
Carcinogenicity Non-carcinogens 0.9182
Biodegradation Not ready biodegradable 1.0
Rat acute toxicity 2.9259 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9809
hERG inhibition (predictor II) Inhibitor 0.7381
ADMET data is predicted usingadmetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
Spectrum Spectrum Type Splash Key
Predicted GC-MS Spectrum - GC-MS Predicted GC-MS Not Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available

Targets

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Details 1.Sodium channel protein type 5 subunit alpha
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Voltage-gated sodium channel activity involved in sa node cell action potential
Specific Function
This protein mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the pr...
Gene Name
SCN5A
Uniprot ID
Q14524
Uniprot Name
Sodium channel protein type 5 subunit alpha
分子魏ght
226937.475 Da
References
  1. Barajas-Martinez HM, Hu D, Cordeiro JM, Wu Y, Kovacs RJ, Meltser H, Kui H, Elena B, Brugada R, Antzelevitch C, Dumaine R: Lidocaine-induced Brugada syndrome phenotype linked to a novel double mutation in the cardiac sodium channel. Circ Res. 2008 Aug 15;103(4):396-404. doi: 10.1161/CIRCRESAHA.108.172619. Epub 2008 Jul 3. [Article]
  2. Khodorov BI, Zaborovskaya LD: Blockade of sodium and potassium channels in the node of Ranvier by ajmaline and N-propyl ajmaline. Gen Physiol Biophys. 1983 Aug;2(4):233-68. [Article]
  3. Hermida JS, Dassonvalle E, Six I, Amant C, Coviaux F, Clerc J, Herent D, Hermida A, Rochette J, Jarry G: Prospective evaluation of the familial prevalence of the brugada syndrome. Am J Cardiol. 2010 Dec 15;106(12):1758-62. doi: 10.1016/j.amjcard.2010.07.049. [Article]
  4. Hoogendijk MG, Potse M, Vinet A, de Bakker JM, Coronel R: ST segment elevation by current-to-load mismatch: an experimental and computational study. Heart Rhythm. 2011 Jan;8(1):111-8. doi: 10.1016/j.hrthm.2010.09.066. Epub 2010 Oct 30. [Article]
  5. Leoni AL, Gavillet B, Rougier JS, Marionneau C, Probst V, Le Scouarnec S, Schott JJ, Demolombe S, Bruneval P, Huang CL, Colledge WH, Grace AA, Le Marec H, Wilde AA, Mohler PJ, Escande D, Abriel H, Charpentier F: Variable Na(v)1.5 protein expression from the wild-type allele correlates with the penetrance of cardiac conduction disease in the Scn5a(+/-) mouse model. PLoS One. 2010 Feb 19;5(2):e9298. doi: 10.1371/journal.pone.0009298. [Article]
  6. Hoogendijk MG, Potse M, Linnenbank AC, Verkerk AO, den Ruijter HM, van Amersfoorth SC, Klaver EC, Beekman L, Bezzina CR, Postema PG, Tan HL, Reimer AG, van der Wal AC, Ten Harkel AD, Dalinghaus M, Vinet A, Wilde AA, de Bakker JM, Coronel R: Mechanism of right precordial ST-segment elevation in structural heart disease: excitation failure by current-to-load mismatch. Heart Rhythm. 2010;7(2):238-48. doi: 10.1016/j.hrthm.2009.10.007. Epub 2009 Oct 12. [Article]

Carriers

Details 1.Alpha-1-acid glycoprotein 1
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Not Available
Specific Function
Functions as transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in...
Gene Name
ORM1
Uniprot ID
P02763
Uniprot Name
Alpha-1-acid glycoprotein 1
分子魏ght
23511.38 Da
References
  1. Koppel C, Wagemann A, Martens F: Pharmacokinetics and antiarrhythmic efficacy of intravenous ajmaline in ventricular arrhythmia of acute onset. Eur J Drug Metab Pharmacokinet. 1989 Apr-Jun;14(2):161-7. [Article]

Drug created at July 24, 2007 12:27 / Updated at September 25, 2021 23:52