BESIPIRDINE HYDROCHLORIDE

Possibly Marketed Outside US

Details

Stereochemistry	ACHIRAL
Molecular Formula	C16H17N3.ClH
Molecular Weight	287.787
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

Cl.CCCN(N1C=CC2=C1C=CC=C2)C3=CC=NC=C3

InChI

InChIKey=ZDFVWDHZXAGROF-UHFFFAOYSA-N

InChI=1S/C16H17N3.ClH/c1-2-12-18(15-7-10-17-11-8-15)19-13-9-14-5-3-4-6-16(14)19;/h3-11,13H,2,12H2,1H3;1H

HIDE SMILES / InChI

Description
Sources: http://urogene.free.fr/besipirdine.php
Curator's Comment: description was created based on several sources, including: http://www.evaluategroup.com/Universal/View.aspx?type=Story&id=269038 | http://adisinsight.springer.com/drugs/800001339 | https://www.ncbi.nlm.nih.gov/pubmed/9103515 | https://www.ncbi.nlm.nih.gov/pubmed/7674813

Besipirdine is a potential novel first-in-class oral treatment for over active bladder currently in Phase II development, with a mechanism of action clearly different from that of antimuscarinics. It was under evaluation by Aventis up to phase III for Alzheimer’s disease, involving the administration of the compound to over 1500 patients. However, this research has been discontinued. Besipirdine antagonizes alpha-2 and alpha-1 adrenoceptors and inhibits both norepinephrine and serotonin uptake. The most common adverse events were asymptomatic postural hypotension and asymptomatic bradycardia.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Adrenergic receptor alpha-1 169 Target ID: CHEMBL1907610 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9103515 \| http://adisinsight.springer.com/drugs/800001339	Antagonist 2778	5.66 µM [Ki]
Adrenergic receptor alpha-2 113 Target ID: CHEMBL2093864 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9103515 \| http://adisinsight.springer.com/drugs/800001339	Antagonist 2778	0.38 µM [Ki]
Serotonin 1a (5-HT1a) receptor 172 Target ID: CHEMBL273 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9103515	Binding Agent 1064	17.0 µM [IC50]
Voltage-dependent sodium channel (rat) 2 Target ID: Voltage-dependent sodium channel (rat) Sources: https://www.ncbi.nlm.nih.gov/pubmed/8581286	Inhibitor 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Alzheimer’s disease 272 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8624122	Primary		Phase III 656	Unknown Approved Use Unknown
Overactive bladder 38 Sources: http://adisinsight.springer.com/drugs/800001339 http://www.evaluategroup.com/Universal/View.aspx?type=Story&id=269038	Primary		Phase II 1132	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Determination of HP 749, a potential therapeutic agent for Alzheimer's disease, in plasma by high-performance liquid chromatography.	1991 Dec 6	1818073
HP 749 enhances calcium-independent release of [3H]norepinephrine from rat cortical slices and synaptosomes.	1994 Oct	7891842
The pharmacokinetics and cardiovascular pharmacodynamics of HP 749 (besipirdine HCl) and metabolite P86-7480 in the conscious monkey.	1995 Jul	7560249

Patents

Sample Use Guides

In Vivo Use Guide

5 and 20 mg b.i.d.

Route of Administration: Oral

In Vitro Use Guide

Besipirdine inhibited [3H]-batrachotoxin binding (IC50 = 5.5 uM) in a rat brain vesicular preparation and concentration-dependently inhibited veratridine (25 uM)-stimulated increases in intracellular free sodium ([Na+]i) and calcium ([Ca2+]i) in primary cultured cortical neurones of rat. Besipirdine (30-100 uM) concentration-dependently inhibited (up to 100%) veratridine-stimulated release of [3H]-noradrenaline (NA) from rat cortical slices.

Name

Type

Language

BESIPIRDINE HYDROCHLORIDE

Official Name

English

1H-INDOL-1-AMINE, N-PROPYL-N-4-PYRIDINYL-, MONOHYDROCHLORIDE

Common Name

English

1-(Propyl-4-pyridylamino)indole monohydrochloride

Systematic Name

English

Besipirdine hydrochloride [WHO-DD]

Common Name

English

HP-749

Code

English

BESIPIRDINE HCL

Common Name

English

HP 749

Code

English

BESIPIRDINE HYDROCHLORIDE [USAN]

Common Name

English

BESIPIRDINE HYDROCHLORIDE [MI]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C87053