LAPPACONITINE HYDROBROMIDE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C32H44N2O8.BrH
Molecular Weight	665.612
Optical Activity	UNSPECIFIED
Defined Stereocenters	12 / 12
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

Br.CCN1C[C@@]2(CC[C@H](OC)[C@@]34[C@@H]5C[C@H]6[C@H](OC)[C@]5(O)[C@](O)(C[C@@H]6OC)[C@@H](C[C@H]23)[C@@H]14)OC(=O)C7=CC=CC=C7NC(C)=O

InChI

InChIKey=CFFYROOPXPKMEQ-IPZKEBFRSA-N

InChI=1S/C32H44N2O8.BrH/c1-6-34-16-29(42-28(36)18-9-7-8-10-21(18)33-17(2)35)12-11-25(40-4)31-23(29)14-20(26(31)34)30(37)15-22(39-3)19-13-24(31)32(30,38)27(19)41-5;/h7-10,19-20,22-27,37-38H,6,11-16H2,1-5H3,(H,33,35);1H/t19-,20+,22+,23-,24+,25+,26-,27+,29-,30+,31+,32+;/m1./s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/28463565 | https://www.ncbi.nlm.nih.gov/pubmed/25796978 | https://www.ncbi.nlm.nih.gov/pubmed/3207434 | http://en.pharmacodia.com/web/drug/1_21542.htmlhttp://www.rlsnet.ru/tn_index_id_73352.htm

Lappaconitine is an alkaloid isolated from the root of Aconltitum sinomantanum Nakai. It has a strong analgesic activity that does not involve the opioid receptor. It was shown to have class-I antiarrhythmic action and irreversibly blocks cloned human heart (hH1) channels by binding to the site 2 receptor.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Acetylcholinesterase 209 Target ID: CHEMBL220 Sources: https://www.ncbi.nlm.nih.gov/pubmed/28463565	Inhibitor 8504	6.13 µM [IC50]
sodium channel activity 16 Target ID: GO:0005272 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9459571 \| https://www.ncbi.nlm.nih.gov/pubmed/20594622	Inhibitor 8504	14.1 µM [IC50]
P2X purinoceptor 3 9 Target ID: CHEMBL4824 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21272608	Antagonist 2849
Sodium channel protein type V alpha subunit 49 Target ID: CHEMBL1980 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11160852	Blocker 555
Sodium channel protein type V alpha subunit 49 Target ID: CHEMBL1980 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11160852	Blocker 555

Conditions

Condition	Modality	Highest Phase	Product
Pain 619 Sources: https://www.ncbi.nlm.nih.gov/pubmed/3207434 https://www.ncbi.nlm.nih.gov/pubmed/21272608	Primary	Phase I 438	Unknown Approved Use Unknown
Arrhythmia 45 Sources: http://en.pharmacodia.com/web/drug/1_21542.html http://adisinsight.springer.com/drugs/800002254	Primary	Phase II 1147	Unknown Approved Use Unknown
Postoperative pain 22 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26242116	Palliative	Phase II 1147	Unknown Approved Use Unknown
Pre-excitation syndromes 3 Sources: http://www.rlsnet.ru/tn_index_id_4134.htm	Primary	Approved 8583	ALLAPININ Approved Use Excerts membrane stabilizing action, influences sodium channels, belongs to IC class of antiarrhythmic agents. Causes slowing of atrioventricular and intraventricular condution, shortens the effective and functional refractory periods in the atria and ventricles. Does does not affect the duration of the interval QT, conductivity in the AV node anterograde direction, heart rate and blood pressure, myocardial contractility (in the absence of heart failure events). Provides moderate antispasmodic, vasodilating, cholinolytic and sedative effect.
Supraventricular tachycardia 8 Sources: http://www.rlsnet.ru/tn_index_id_4134.htm	Primary	Approved 8583	ALLAPININ Approved Use Excerts membrane stabilizing action, influences sodium channels, belongs to IC class of antiarrhythmic agents. Causes slowing of atrioventricular and intraventricular condution, shortens the effective and functional refractory periods in the atria and ventricles. Does does not affect the duration of the interval QT, conductivity in the AV node anterograde direction, heart rate and blood pressure, myocardial contractility (in the absence of heart failure events). Provides moderate antispasmodic, vasodilating, cholinolytic and sedative effect.
Premature depolarization, unspecified 3 Sources: http://www.rlsnet.ru/tn_index_id_4134.htm	Primary	Approved 8583	ALLAPININ Approved Use Excerts membrane stabilizing action, influences sodium channels, belongs to IC class of antiarrhythmic agents. Causes slowing of atrioventricular and intraventricular condution, shortens the effective and functional refractory periods in the atria and ventricles. Does does not affect the duration of the interval QT, conductivity in the AV node anterograde direction, heart rate and blood pressure, myocardial contractility (in the absence of heart failure events). Provides moderate antispasmodic, vasodilating, cholinolytic and sedative effect.
Atrial fibrillation and flutter 3 Sources: http://www.rlsnet.ru/tn_index_id_4134.htm	Primary	Approved 8583	ALLAPININ Approved Use Excerts membrane stabilizing action, influences sodium channels, belongs to IC class of antiarrhythmic agents. Causes slowing of atrioventricular and intraventricular condution, shortens the effective and functional refractory periods in the atria and ventricles. Does does not affect the duration of the interval QT, conductivity in the AV node anterograde direction, heart rate and blood pressure, myocardial contractility (in the absence of heart failure events). Provides moderate antispasmodic, vasodilating, cholinolytic and sedative effect.
Ventricular tachycardia 11 Sources: http://www.rlsnet.ru/tn_index_id_4134.htm	Primary	Approved 8583	ALLAPININ Approved Use Excerts membrane stabilizing action, influences sodium channels, belongs to IC class of antiarrhythmic agents. Causes slowing of atrioventricular and intraventricular condution, shortens the effective and functional refractory periods in the atria and ventricles. Does does not affect the duration of the interval QT, conductivity in the AV node anterograde direction, heart rate and blood pressure, myocardial contractility (in the absence of heart failure events). Provides moderate antispasmodic, vasodilating, cholinolytic and sedative effect.

C_max

Value	Dose	Co-administered	Analyte	Population
5.09 ng/mL EXPERIMENT https://www.pharmjournal.ru/jour/article/view/1172?locale=en_US	25 mg single, oral dose: 25 mg route of administration: Oral experiment type: SINGLE co-administered:		LAPPACONITINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
11.66 ng/mL EXPERIMENT https://www.pharmjournal.ru/jour/article/view/1172?locale=en_US	25 mg single, oral dose: 25 mg route of administration: Oral experiment type: SINGLE co-administered:		N-DESACETYLLAPPACONITINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
71.24 ng × h/mL EXPERIMENT https://www.pharmjournal.ru/jour/article/view/1172?locale=en_US	25 mg single, oral dose: 25 mg route of administration: Oral experiment type: SINGLE co-administered:		LAPPACONITINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
189.42 ng × h/mL EXPERIMENT https://www.pharmjournal.ru/jour/article/view/1172?locale=en_US	25 mg single, oral dose: 25 mg route of administration: Oral experiment type: SINGLE co-administered:		N-DESACETYLLAPPACONITINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
8.45 h EXPERIMENT https://www.pharmjournal.ru/jour/article/view/1172?locale=en_US	25 mg single, oral dose: 25 mg route of administration: Oral experiment type: SINGLE co-administered:		LAPPACONITINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
9.04 h EXPERIMENT https://www.pharmjournal.ru/jour/article/view/1172?locale=en_US	25 mg single, oral dose: 25 mg route of administration: Oral experiment type: SINGLE co-administered:		N-DESACETYLLAPPACONITINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

PubMed

Title	Date	PubMed
Selective dual cholinesterase inhibitors from Aconitum laeve.	2018-02	28463565
Comparative metabolism of Lappaconitine in rat and human liver microsomes and in vivo of rat using ultra high-performance liquid chromatography-quadrupole/time-of-flight mass spectrometry.	2015-06-10	25796978
Irreversible block of human heart (hH1) sodium channels by the plant alkaloid lappaconitine.	2001-02	11160852
Pharmacological studies of lappaconitine. Analgesic activities.	1988-07	3207434

Patents

Sample Use Guides

In Vivo Use Guide

Lappaconitine (8 mg) was intravenously dripped to patients in the lappaconitine group 30 min before ending the operation. PCIA started as soon as the end of the surgery and the total dose of lappaconitine was 36 mg.

Route of Administration: Intravenous

In Vitro Use Guide

Right isolated guinea-pig atria became bradycardic at 3 uM lappaconitine, and at 4.5 uM one of six right atria ceased contracting. Asystolia was also observed in left atria at concentrations about 600 nM, but all of the asystolic atria resumed contraction as the stimulation current was increased, indicating an elevation of the excitation threshold.

Name

Type

Language

ALLAFORT

Preferred Name

English

LAPPACONITINE HYDROBROMIDE

Common Name

English

ACONITANE-4,8,9-TRIOL, 20-ETHYL-1,14,16-TRIMETHOXY-, 4-(2-(ACETYLAMINO)BENZOATE), MONOHYDROBROMIDE, (1.ALPHA.,14.ALPHA.,16.BETA.)-

Systematic Name

English

ALLAPININE

Common Name

English

ACONITANE-4,8,9-TRIOL, 20-ETHYL-1,14,16-TRIMETHOXY-, 4-(2-(ACETYLAMINO)BENZOATE), HYDROBROMIDE (1:1), (1.ALPHA.,14.ALPHA.,16.BETA.)-

Systematic Name

English

Lappaconitine hydrobromide [WHO-DD]

Common Name

English

Code System Code Type Description

PUBCHEM

90479363