PIMETHIXENE MALEATE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C19H19NS.C4H4O4
Molecular Weight	409.498
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC(=O)\C=C/C(O)=O.CN1CCC(CC1)=C2C3=CC=CC=C3SC4=CC=CC=C24

InChI

InChIKey=IPANUAHQWFDVAG-BTJKTKAUSA-N

InChI=1S/C19H19NS.C4H4O4/c1-20-12-10-14(11-13-20)19-15-6-2-4-8-17(15)21-18-9-5-3-7-16(18)19;5-3(6)1-2-4(7)8/h2-9H,10-13H2,1H3;1-2H,(H,5,6)(H,7,8)/b;2-1-

HIDE SMILES / InChI

Description
Sources: https://www.drugs.com/international/pimethixene.html | https://www.ncbi.nlm.nih.gov/pubmed/25666387 | http://www.juvisepharmaceuticals.com/wp-content/uploads/2014/07/Notice-Calmixene-0705131.pdf

Pimethixene is an antihistamine exerting sedative and antitussive properties. Pimethixene displayed high affinity to serotonin 5-HT2A and 2B, histamine H1 and muscarinic acetylcholine M2 receptors. Oral pimethixene used to calm dry cough and irritation coughs in children.

CNS Activity

Approval Year

Targets

Primary Target	Pharmacology	Potency
Histamine H1 receptor 316 Target ID: CHEMBL231 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25666387	Antagonist 2849	10.14 null [pKi]
Muscarinic acetylcholine receptor M2 121 Target ID: CHEMBL211 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25666387	Antagonist 2849	9.38 null [pKi]
Serotonin 2a (5-HT2a) receptor 237 Target ID: CHEMBL224 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25666387	Antagonist 2849	10.22 null [pKi]
Serotonin 2b (5-HT2b) receptor 60 Target ID: CHEMBL1833 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25666387	Antagonist 2849	10.44 null [pKi]

Conditions

Condition	Modality	Highest Phase	Product
Cough 106 Sources: http://www.juvisepharmaceuticals.com/wp-content/uploads/2014/07/Notice-Calmixene-0705131.pdf http://www.bulas.med.br/p/bulas-de-medicamentos/bula/3123/muricalm.htm	Primary	Approved 8583	CALMIXENE Approved Use It is recommended to calm dry cough and irritation coughs in children older than 2 years, especially when they occur in the evening or at night
Allergy 44 Sources: https://www.ncbi.nlm.nih.gov/pubmed/13948138 https://www.ncbi.nlm.nih.gov/pubmed/14084232	Primary	Not Provided 511	Unknown Approved Use Unknown
Asthma 244 Sources: https://www.ncbi.nlm.nih.gov/pubmed/14059854 https://www.ncbi.nlm.nih.gov/pubmed/14279395	Primary	Not Provided 511	Unknown Approved Use Unknown

Doses

Dose	Population	Adverse events
4 mg single, intravenous Highest studied dose Dose: 4 mg Route: intravenous Route: single Dose: 4 mg Sources: https://pubmed.ncbi.nlm.nih.gov/14059854/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/14059854/	Other AEs: Dizziness, Burning leg... Other AEs: Dizziness (grade 1-2, 44%) Burning leg (19%) Pricking in the extremities (19%) Drowsiness Fell asleep Fatigue Sources: https://pubmed.ncbi.nlm.nih.gov/14059854/

AEs

AE	Significance	Dose	Population
Drowsiness		4 mg single, intravenous Highest studied dose Dose: 4 mg Route: intravenous Route: single Dose: 4 mg Sources: https://pubmed.ncbi.nlm.nih.gov/14059854/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/14059854/
Fatigue		4 mg single, intravenous Highest studied dose Dose: 4 mg Route: intravenous Route: single Dose: 4 mg Sources: https://pubmed.ncbi.nlm.nih.gov/14059854/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/14059854/
Fell asleep		4 mg single, intravenous Highest studied dose Dose: 4 mg Route: intravenous Route: single Dose: 4 mg Sources: https://pubmed.ncbi.nlm.nih.gov/14059854/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/14059854/
Burning leg	19%	4 mg single, intravenous Highest studied dose Dose: 4 mg Route: intravenous Route: single Dose: 4 mg Sources: https://pubmed.ncbi.nlm.nih.gov/14059854/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/14059854/
Pricking in the extremities	19%	4 mg single, intravenous Highest studied dose Dose: 4 mg Route: intravenous Route: single Dose: 4 mg Sources: https://pubmed.ncbi.nlm.nih.gov/14059854/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/14059854/
Dizziness	grade 1-2, 44%	4 mg single, intravenous Highest studied dose Dose: 4 mg Route: intravenous Route: single Dose: 4 mg Sources: https://pubmed.ncbi.nlm.nih.gov/14059854/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/14059854/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 2252	inhibitor 2438	inhibitor 2507

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2C19 2057 CYP1A2 2153

Drug as perpetrator

Target	Modality	Activity
CYP2C19 2141	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzNjIyIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDE1MjQwOCJ9fQ==	inconclusive [IC50 15.8489 uM]
CYP1A2 2333	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzMzU2IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDE1MjQwOCJ9fQ==	no [IC50 >10 uM]
CYP2C9 2497	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzMzk3IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDE1MjQwOCJ9fQ==	no [IC50 >10 uM]
CYP3A4 2633	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzNDAiLCJ1c2VfY3VzdG9tX3F1ZXJ5Ijp0cnVlLCJzZWFyY2hfdGVybSI6IiIsInRleHRfZmlsdGVyIjoiQ0hFTUJMMTUyNDA4In19	no [IC50 >10 uM]
CYP2D6 2546	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwyODkiLCJ1c2VfY3VzdG9tX3F1ZXJ5Ijp0cnVlLCJzZWFyY2hfdGVybSI6IiIsInRleHRfZmlsdGVyIjoiQ0hFTUJMMTUyNDA4In19	yes [IC50 3.9811 uM]

PubMed

Title	Date	PubMed
BF-1--a novel selective 5-HT2B receptor antagonist blocking neurogenic dural plasma protein extravasation in guinea pigs.	2015-03-15	25666387
LuxR-dependent quorum sensing: computer aided discovery of new inhibitors structurally unrelated to N-acylhomoserine lactones.	2010-08-01	20615699
[New treatment of hyperkinesis in the child: pimethixene].	1978-07-15	674966
[On the pharmacology of 9,10-dihydro-10-(1-methyl-4-piperidylidene)-9-anthrol (WA 335), a histamine and serotonin antagonist (author's transl)].	1975-11	1049
[Clinical experience with the application of pimethixene in the premedication of children].	1967-09	4384909
[PRELIMINARY FINDINGS ON THE USE OF 9-(METHYL-4'-PIPERIDYLIDENE)-THIOXANTHENE (BP 400) IN THE TREATMENT OF OBSTRUCTIVE RESPIRATORY INSUFFICIENCY].	1963-10	14279395
[Clinical trials of a new antiallergic substance, 9-(N-methyl-4-piperidylidene)-thioxasthene (BP 400)].	1963-03-16	13948138
[ANTIANAPHYLACTIC PROPERTIES OF 9-(N-METHYL-4'-PIPERIDYLIDENE) THIOXANTHENE (BP 400) AND LYSOZYME, COMPARED TO THOSE OF PREDNISONE].	1963	14084232
BP 400 IN BRONCHIAL ASTHMA.	1963	14059854

Patents

Sample Use Guides

In Vivo Use Guide

Children from 24 to 30 months: 2 to 3 dosing cups (graduation at 5 ml) distributed over the day, Children from 30 months to 5 years: 3 to 4 dosing cups (graduation at 5 ml) distributed over the day, Children from 5 to 15 years: 5 to 6 dosing cups (graduation at 5 ml) distributed over the day. The strongest dose will be kept for the evening due to the possibility of drowsiness related with this medicine

Route of Administration: Oral

In Vitro Use Guide

Unknown

Name

Type

Language

PIMETHIXENE MALEATE

Common Name

English

PIMETHIXENE MALEATE SALT

Preferred Name

English

Pimethixene maleate [WHO-DD]

Common Name

English

1-METHYL-4-(THIOXANTHEN-9-YLIDENE)PIPERIDINE MALEATE

Systematic Name

English

Classification Tree Code System Code

NCI_THESAURUS

C29578