ACONITINE HYDROBROMIDE

US Previously Marketed

First marketed in 1921

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C34H47NO11.BrH
Molecular Weight	726.649
Optical Activity	UNSPECIFIED
Defined Stereocenters	15 / 15
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

Br.[H][C@@]12[C@H]3C[C@@](O)([C@@H]1OC(=O)C4=CC=CC=C4)[C@@H](OC)[C@H](O)[C@]2(OC(C)=O)[C@H]5[C@H](OC)[C@@]6([H])[C@]37C5N(CC)C[C@]6(COC)[C@H](O)C[C@@H]7OC

InChI

InChIKey=QKBOPFIDNJPMBP-PHFVEKHWSA-N

InChI=1S/C34H47NO11.BrH/c1-7-35-15-31(16-41-3)20(37)13-21(42-4)33-19-14-32(40)28(45-30(39)18-11-9-8-10-12-18)22(19)34(46-17(2)36,27(38)29(32)44-6)23(26(33)35)24(43-5)25(31)33;/h8-12,19-29,37-38,40H,7,13-16H2,1-6H3;1H/t19-,20-,21+,22-,23+,24+,25-,26-,27+,28-,29+,31+,32-,33+,34-;/m1./s1

HIDE SMILES / InChI

Molecular Formula	C34H47NO11
Molecular Weight	645.7371
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	12 / 15
E/Z Centers	0
Optical Activity	UNSPECIFIED

Molecular Formula	BrH
Molecular Weight	80.912
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: http://abcdef.uni-hd.de/institute/fak14/ipmb/phazb/pubwink/1998/15.%201998.pdf | https://www.ncbi.nlm.nih.gov/pubmed/7839574 | https://www.ncbi.nlm.nih.gov/pubmed/8082861

Aconitine is an alkaloid found in the Aconitum species. Aconitine is a highly toxic cardiotoxin and neurotoxin. In China and other countries, the herbal extract containing aconitine was used for the treatment of pain in musculoskeletal disorders, however the safety margin between therapeutic analgesic effect of aconitine and its known cardiotoxic effect is so narrow that the treatment may cause poisoning and death. The mechanism of aconitine action is explained by its ability to activate voltage-dependent sodium-ion channels.

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Voltage-dependent sodium-ion channels 3 Target ID: Voltage-dependent sodium-ion channels Sources: http://abcdef.uni-hd.de/institute/fak14/ipmb/phazb/pubwink/1998/15.%201998.pdf	Activator 1430

Conditions

Condition	Modality	Targets	Highest Phase	Product
Musculoskeletal disorders 10 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8082861	Palliative		Not Provided 504	Unknown Approved Use Unknown

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737	substrate 1037	substrate 1217	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
OATP1B1 788 OATP1B3 706 OCT2 647 OAT1 599 Nav1.5 97 Cav1.2 45 Kv1.5 26	OATP1B1 406 OATP1B3 350 OATP2B1 104 OCT1 327 OCT3 80 OAT3 339 P-gp 1537 BCRP 561 MRP2 205 CYP3A5 395 CYP1A2 1054 CYP2C8 693 CYP2C19 991 CYP2E1 667	P-gp 257

Drug as perpetrator

Target	Modality	Activity
OATP1B3 715	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/20448812/	no
OATP1B1 803	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/20448812/	weak [IC50 >100 uM]
OAT1 603	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/21561794/	weak
Kv1.5 41	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/20600762/	yes [IC50 0.796 uM]
OCT2 648	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/23770354/	yes [IC50 59.2 uM]
P-gp 1650	activator 214 Sources: https://pubmed.ncbi.nlm.nih.gov/27139035/	yes
P-gp 1650	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/27139035/	yes

Drug as victim

Target	Modality	Activity
CYP2D6 1217	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/21277363/	major
CYP3A4 1737	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/21277363/	major
CYP3A5 395	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/21277363/	major
CYP2C8 693	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/21277363/	minor
CYP2C9 1037	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/21277363/	minor
CYP1A2 1054	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/21277363/	no
CYP2C19 991	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/21277363/	no
CYP2E1 667	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/21277363/	no
BCRP 561	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/23200901/	yes
MRP2 205	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/23200901/ \| https://pubmed.ncbi.nlm.nih.gov/23562926/	yes
OAT3 339	substrate 3367 Sources: https://pubs.rsc.org/en/content/articlehtml/2019/ra/c9ra00393b	yes
OATP1B1 406	substrate 3367 Sources: https://pubs.rsc.org/en/content/articlehtml/2019/ra/c9ra00393b	yes
OATP1B3 350	substrate 3367 Sources: https://pubs.rsc.org/en/content/articlehtml/2019/ra/c9ra00393b	yes
OATP2B1 104	substrate 3367 Sources: https://pubs.rsc.org/en/content/articlehtml/2019/ra/c9ra00393b	yes
OCT1 327	substrate 3367 Sources: https://pubs.rsc.org/en/content/articlehtml/2019/ra/c9ra00393b	yes
OCT3 80	substrate 3367 Sources: https://pubs.rsc.org/en/content/articlehtml/2019/ra/c9ra00393b	yes
P-gp 1537	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/23200901/ \| https://pubmed.ncbi.nlm.nih.gov/23562926/	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
Cav1.2 49	inhibitor 1626 Sources: https://pubmed.ncbi.nlm.nih.gov/28056022/
Nav1.5 100	inhibitor 1626 Sources: https://pubmed.ncbi.nlm.nih.gov/28056022/
hERG 1647	inhibitor 1626 Sources: https://pubmed.ncbi.nlm.nih.gov/28056022/ \| https://pubmed.ncbi.nlm.nih.gov/20600762/

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:2430	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:2430
MolPort	MolPort-002-527-310	https://www.molport.com/shop/molecule-link/MolPort-002-527-310
eMolecules	26424222	https://www.emolecules.com/cgi-bin/more?vid=26424222

PubMed

Title	Date	PubMed
Acute and chronic nicotine exposure reverse age-related declines in the induction of long-term potentiation in the rat hippocampus.	2001 Mar 16	11251214
The nicotinic antagonist methyllycaconitine has differential effects on nicotine self-administration and nicotine withdrawal in the rat.	2001 Nov	11694204
Dorsal root ganglion neurons express multiple nicotinic acetylcholine receptor subtypes.	2001 Oct	11600638
[Antiarrhythmic drug allapinin: review of results of clinical investigation].	2002	12494120
Synaptic potentials mediated by alpha 7 nicotinic acetylcholine receptors in supraoptic nucleus.	2002 Jan 1	11756485
Effect of garlic on cardiovascular disorders: a review.	2002 Nov 19	12537594
[Study on metabolites on aconitine in rabbit urine].	2002 Oct	12567861
Evidence suggesting that the mouse sperm acrosome reaction initiated by the zona pellucida involves an alpha7 nicotinic acetylcholine receptor.	2003 Apr	12606407
Contribution of functional voltage-gated Na+ channel expression to cell behaviors involved in the metastatic cascade in rat prostate cancer: I. Lateral motility.	2003 Jun	12704658
Carbamoylcholine homologs: novel and potent agonists at neuronal nicotinic acetylcholine receptors.	2003 Oct	14500743
Characterization of aconitine-type alkaloids in the flowers of Aconitum kusnezoffii by electrospray ionization tandem mass spectrometry.	2003 Sep	14505324
A QSAR analysis of toxicity of Aconitum alkaloids.	2004 Dec	15548242
A QSAR toxicity study of a series of alkaloids with the lycoctonine skeleton.	2004 Dec 31	18007512
[Emergency treatment of 4 patients with acute severe intoxication of radix aconiti ferus].	2004 Mar	15074107
Different firing patterns induced by veratridine and aconitine in injured dorsal root ganglion neurons.	2005 Apr 25	15834502
Desensitization of neuronal nicotinic receptors of human neuroblastoma SH-SY5Y cells during short or long exposure to nicotine.	2005 Dec	16230999
Methyllycaconitine prevents methamphetamine-induced effects in mouse striatum: involvement of alpha7 nicotinic receptors.	2005 Nov	16076935
Simultaneous determination of six Aconitum alkaloids in proprietary Chinese medicines by high-performance liquid chromatography.	2005 Nov 4	16233884
Effects of alpha4beta2 and alpha7 nicotinic acetylcholine receptor antagonists on place aversion induced by naloxone in single-dose morphine-treated rats.	2005 Sep 5	16098507
Effects of chronic administrations of aconitine on body weight and rectal temperature in mice.	2006 Apr 21	16293382
Characterization of metabolites and cytochrome P450 isoforms involved in the microsomal metabolism of aconitine.	2006 Dec 5	16949890
Effects of processed Aconiti tuber and its ingredient alkaloids on the development of antinociceptive tolerance to morphine.	2006 Feb 20	16169697
Evaluation of the role of nicotinic acetylcholine receptor subtypes and cannabinoid system in the discriminative stimulus effects of nicotine in rats.	2006 Jul 1	16730696
Nicotine reverses consolidated long-term potentiation in the hippocampal CA1 region.	2006 Mar 17	16564510
Individual differences in response to novelty predict prefrontal cortex dopamine transporter function and cell surface expression.	2007 Aug	17651428
Combinative method using HPLC quantitative and qualitative analyses for quality consistency assessment of a herbal medicinal preparation.	2007 Jan 4	16920317
The beta-amyloid protein of Alzheimer's disease binds to membrane lipids but does not bind to the alpha7 nicotinic acetylcholine receptor.	2007 Jun	17286584
[Studies on hydrolysis of aconitine].	2007 Oct	18306748
Nicotinic acetylcholine alpha4beta2 receptor regulates the motivational effect of intracranial self stimulation behavior in the runway method.	2008 Dec	19057129
Choline produces antiarrhythmic actions in animal models by cardiac M3 receptors: improvement of intracellular Ca2+ handling as a common mechanism.	2008 Dec	19088807
Differential coupling of M1 muscarinic and alpha7 nicotinic receptors to inhibition of pemphigus acantholysis.	2008 Feb 8	18073210
Daphniphyllum and diterpenoid alkaloids from Daphniphyllum longeracemosum.	2008 Jul	18553922
Characterization of aconitine-induced block of delayed rectifier K+ current in differentiated NG108-15 neuronal cells.	2008 May	18336846
[The role of reflexotherapy and physical training in the combined treatment and the prevention of paroxysmal form of idiopathic atrial fibrillation].	2008 Nov-Dec	19175054
Effects of aconitine on [Ca2+] oscillation in cultured myocytes of neonatal rats.	2008 Oct	18846325
Status epilepticus induces cardiac myofilament damage and increased susceptibility to arrhythmias in rats.	2009 Dec	19820194
Characterization of compounds on nicotinic acetylcholine receptor alpha7 channels using higher throughput electrophysiology.	2009 Feb 15	19000713
Nicotine induces cell proliferation, invasion and epithelial-mesenchymal transition in a variety of human cancer cell lines.	2009 Jan 1	18844224
Serum elimination profiles of methyllycaconitine and deltaline in cattle following oral administration of larkspur (Delphinium barbeyi).	2009 Jul	19566479
Stability-indicating reversed-phase liquid chromatographic methods for the determination of aconitine and piperine in a polyherbal formulation.	2009 Jul-Aug	19714970
Studies on the aconitine-type alkaloids in the roots of Aconitum Carmichaeli Debx. by HPLC/ESIMS/MS(n).	2009 Mar 15	19159802
The involvement of nicotinic receptor subtypes in the locomotor activity and analgesia induced by methamphetamine in mice.	2009 Oct	19741505
Nicotinic antagonist effects in the mediodorsal thalamic nucleus: regional heterogeneity of nicotinic receptor involvement in cognitive function.	2009 Oct 1	19477167
Lidocaine inhibits epithelial chemokine secretion via inhibition of nuclear factor kappa B activation.	2010 Apr	19559500
[Difference of hypaconitine concentration in serum between cold-deficiency and normal mice].	2010 Aug	20931857
Aconitine blocks HERG and Kv1.5 potassium channels.	2010 Aug 19	20600762
Antillatoxin is a sodium channel activator that displays unique efficacy in heterologously expressed rNav1.2, rNav1.4 and rNav1.5 α subunits.	2010 Dec 14	21156065
The histone deacetylase inhibitor suberoylanilide hydroxamic acid reduces cardiac arrhythmias in dystrophic mice.	2010 Jul 1	20164117
Simultaneous determination of six alkaloids in blood and urine using a hydrophilic interaction liquid chromatography method coupled with electrospray ionization tandem mass spectrometry.	2010 Oct	20665006
Transcellular transport of aconitine across human intestinal Caco-2 cells.	2013 Jul	23562926

Patents

Sample Use Guides

In Vivo Use Guide

Unknown

Route of Administration: Unknown

In Vitro Use Guide

When added at concentration of 3 uM, aconitine depolarized rat ventromedial hypothalamic neurons.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 09:29:50 GMT 2023` Edited by `admin` on `Sat Dec 16 09:29:50 GMT 2023`
Record UNII	US306163EJ
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

ACONITINE HYDROBROMIDE

Common Name

English

ACONITINE HYDROBROMIDE ANHYDROUS

Common Name

English

ACONITINE HYDROBROMIDE ANHYDROUS [MI]

Common Name

English

ACONITANE-3,8,13,14,15-PENTOL, 20-ETHYL-1,6,16-TRIMETHOXY-4-(METHOXYMETHYL)-, 8-ACETATE 14-BENZOATE, HYDROBROMIDE (1:1), (1.ALPHA.,3.ALPHA.,6.ALPHA.,14.ALPHA.,15.ALPHA.,16.BETA.)-

Systematic Name

English

Code System Code Type Description

FDA UNII

US306163EJ