NAFTOPIDIL DIHYDROCHLORIDE

Details

Stereochemistry	RACEMIC
Molecular Formula	C24H28N2O3.2ClH
Molecular Weight	465.413
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

Cl.Cl.COC1=C(C=CC=C1)N2CCN(CC(O)COC3=CC=CC4=C3C=CC=C4)CC2

InChI

InChIKey=HZVCEQMJXMUXJF-UHFFFAOYSA-N

InChI=1S/C24H28N2O3.2ClH/c1-28-24-11-5-4-10-22(24)26-15-13-25(14-16-26)17-20(27)18-29-23-12-6-8-19-7-2-3-9-21(19)23;;/h2-12,20,27H,13-18H2,1H3;2*1H

HIDE SMILES / InChI

Description
Sources: http://www.asahi-kasei.co.jp/asahi/en/news/2011/e120110.html
Curator's Comment: description was created based on several sources, including http://www.ncbi.nlm.nih.gov/pubmed/23554846 http://www.ncbi.nlm.nih.gov/pubmed/19233432

Naftopidil (INN, marketed under the brand name Flivas) is a drug used in benign prostatic hypertrophy which acts as a selective alpha1-adrenergic receptor antagonist, has been used for the treatment of benign prostatic obstruction and benign prostatic hyperplasia (BPH) associated lower urinary tract symptoms (LUTS). The Japanese Ministry of Health, Labor and Welfare approved naftopidil for treating men with BPH in 1996. Although well-designed, randomized studies are warranted to confirm the long-term outcomes and effector/target of naftopidil, the α1A-antagonist naftopidil, which also blocks α1D-adrenoceptor, improves voiding symptoms, and may also be useful for the management of men with storage symptoms represented by nocturia, retrieving their quality of life impaired by BPH-associated LUTS. The selective alpha1D-blocker naftopidil can significantly facilitate spontaneous passage of distal ureteral stones with few side effects, providing a new choice for medical expulsive therapy.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Alpha-1A adrenergic receptor 19 Target ID: P35348\|\|\|B0ZBD9\|\|\|Q6RUJ8 Gene ID: 148.0 Gene Symbol: ADRA1A Target Organism: Homo sapiens (Human) Sources: http://www.ncbi.nlm.nih.gov/pubmed/10361884	Antagonist 2778	3.7 nM [Ki]
Alpha-1B adrenergic receptor 4 Target ID: P35368 Gene ID: 147.0 Gene Symbol: ADRA1B Target Organism: Homo sapiens (Human) Sources: http://www.ncbi.nlm.nih.gov/pubmed/10361884	Antagonist 2778	20.0 nM [Ki]
Alpha-1D adrenergic receptor 6 Target ID: P25100 Gene ID: 146.0 Gene Symbol: ADRA1D Target Organism: Homo sapiens (Human) Sources: http://www.ncbi.nlm.nih.gov/pubmed/10361884	Antagonist 2778	1.2 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Dysuria associated with benign prostatic hyperplasia 2 Sources: http://www.asahi-kasei.co.jp/asahi/en/news/2011/e120110.html	Secondary		Approved 8429	Unknown Approved Use Unknown
Distal ureteral stones 2 Sources: http://www.ncbi.nlm.nih.gov/pubmed/19233432	Primary		Phase III 656	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Vascular alpha1-adrenoceptor subtype selectivity and alpha1-blocker-induced orthostatic hypotension.	1998 May	9639061
Non-protected fluid room-temperature phosphorimetric procedure for the direct determination of naftopidil in biological fluids.	2001 Dec	11769798
Direct determination of naftopidil by non-protected fluid room temperature phosphorescence.	2001 Feb	11235109
Effects of intrathecal injection of tamsulosin and naftopidil, alpha-1A and -1D adrenergic receptor antagonists, on bladder activity in rats.	2002 Aug 2	12123863
Differential actions of naftopidil, doxazosin and nifedipine on platelet thromboxane generation and platelet-derived growth factor efflux in vitro.	2002 Aug-Sep	12189011
[A comparative study assessing clinical effects of naftopidil and tamsulosin hydrochloride on benign prostatic hyperplasia].	2002 Jan	11868386
[Long-term efficacy of naftopidil for treatment of lower urinary tract symptoms with benign prostatic hyperplasia].	2003 Apr	12784711
Effects of intrathecal injection of tamsulosin and naftopidil, alpha-1A and 1D adrenergic receptor antagonists, on bladder activity in rats.	2003 Apr	12641149
[Clinical effects of naftopidil on nocturia associated with benign prostatic hyperplasia].	2003 Aug	14518379
Effects of tamsulosin on hypogastric nerve stimulation-induced intraurethral pressure elevation in male and female dogs under anesthesia.	2004 Aug 30	15336951
Comparison of tamsulosin and naftopidil for efficacy and safety in the treatment of benign prostatic hyperplasia: a randomized controlled trial.	2005 Sep	16104914
Single-blind, randomized controlled study of the clinical and urodynamic effects of an alpha-blocker (naftopidil) and phytotherapy (eviprostat) in the treatment of benign prostatic hyperplasia.	2005 Sep	16094031
Comparison of two alpha1-adrenoceptor antagonists, naftopidil and tamsulosin hydrochloride, in the treatment of lower urinary tract symptoms with benign prostatic hyperplasia: a randomized crossover study.	2006 Apr	16536766
[The study of the in vivo-in vitro correlation of the naftopidil sustained-release tablet in dog].	2006 Aug	17002117
In vivo studies on the effects of alpha1-adrenoceptor antagonists on pupil diameter and urethral tone in rabbits.	2006 Feb	16489448
Clinical efficacy of an alpha1A/D-adrenoceptor blocker (naftopidil) on overactive bladder symptoms in patients with benign prostatic hyperplasia.	2006 Jan	16448426
[Effect of silodosin on intraurethral pressure increase induced by hypogastric nerve stimulation in dogs with benign prostatic hyperplasia].	2006 Mar	16518087
[Latest frontiers in pharmacotherapy for benign prostatic hyperplasia].	2006 Mar	16518083
Effect of tamsulosin on spontaneous bladder contraction in conscious rats with bladder outlet obstruction: comparison with effect on intraurethral pressure.	2006 Sep 18	16887117
Search for new alpha1a-adrenoceptor-selective antagonist for treating lower urinary tract symptoms associated with benign prostatic hyperplasia.	2007 Apr	19675810
Effects of propiverine and naftopidil on the urinary ATP level and bladder activity after bladder stimulation in rats.	2007 Dec 18	17997223
Crossover comparison study on the therapeutic effects of tamsulosin hydrochloride and naftopidil in lower urinary tract symptoms associated with benign prostatic hyperplasia.	2007 Feb	17401467
[Giant prostate carcinoma treated effectively with endocrine therapy: case report].	2007 Feb	17352166
Incidence of intraoperative floppy iris syndrome in patients on either systemic or topical alpha(1)-adrenoceptor antagonist.	2007 Jan	17188051
[Comparison of different drugs on the treatment of benign prostate hyperplasia].	2007 Jul 15	17961376
Clinical effect of alpha 1D/A adrenoceptor inhibitor naftopidil on benign prostatic hyperplasia: an international prostate symptom score and King's Health Questionnaire assessment.	2008 Aug	18662175
Alpha antagonists and intraoperative floppy iris syndrome: A spectrum.	2008 Dec	19668424
In vivo study on the effects of alpha1-adrenoceptor antagonists on intraurethral pressure in the prostatic urethra and intraluminal pressure in the vas deferens in male dogs.	2008 Feb 2	18078926
[Clinical evaluation of supplemental administration of flavoxate hydrochloride in benign prostatic hyperplasia patients with nocturia resistant to an alpha1-adrenoceptor blocker].	2008 Mar	18411771
[Evaluation of supplemental administration of Eviprostat in patients with benign prostatic hyperplasia with persistent symptoms following treatment with alpha1-adrenoceptor blocker].	2008 May	18546857
Alpha-adrenoceptor blockade modifies neurally induced atrial arrhythmias.	2008 Oct	18716036
Ejaculatory disorders caused by alpha-1 blockers for patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia: comparison of naftopidil and tamsulosin in a randomized multicenter study.	2009	19641359
Role of alpha1-adrenergic receptors in detrusor overactivity induced by cold stress in conscious rats.	2009	18837433
[The clinical efficacy and safety of naftopidil 75 mg on benign prostatic hyperplasia patients with moderate or severe urinary disturbance].	2009 Apr	19462821
Efficacy of selective alpha1D-blocker naftopidil as medical expulsive therapy for distal ureteral stones.	2009 Apr	19233432
Clinical efficacy of naftopidil on lower urinary tract symptoms after radical prostatectomy.	2009 Mar	19207610
The add-on effect of solifenacin for patients with remaining overactive bladder after treatment with tamsulosin for lower urinary tract symptoms suggestive of benign prostatic obstruction.	2010	20981257
[Effects of alpha1 adrenoceptor antagonist, naftopidil, on non-bacterial chronic pelvic pain syndrome in patients with lower urinary tract syndrome: evaluation of its efficacy using NIH-CPSI after 4-week treatment].	2010 Apr	20448445
[Efficacy of naftopidil for nocturia and consequent sleep disturbance in patients with benign prostatic hyperplasia].	2010 Apr	20448444
[A randomized controlled study comparing clinical effects of naftopidil and tamsulosin on benign prostatic hyperplasia].	2010 Sep	20940522

Patents

Sample Use Guides

In Vivo Use Guide

50 or 75 mg/day in Japanese men in clinical practice. For men in the US or European countries, the optimal dose is estimated to be higher

Route of Administration: Oral

In Vitro Use Guide

Naftopidil has growth inhibitory effect in androgen-sensitive and -insensitive human prostate cancer cell lines. The concentrations causing 50% inhibition (IC50) of cancer cell growth were 22.2 +/- 4.0 microM in androgen-sensitive LNCaP cells and 33.2 +/- 1.1 microM in androgen-insensitive PC-3 cells.

Name

Type

Language

NAFTOPIDIL DIHYDROCHLORIDE

Common Name

English

1-PIPERAZINEETHANOL, 4-(2-METHOXYPHENYL)-.ALPHA.-((1-NAPHTHALENYLOXY)METHYL)-, HYDROCHLORIDE (1:2)

Systematic Name

English

NAFTOPIDIL DIHYDROCHLORIDE [MI]

Common Name

English

4-(2-METHOXYPHENYL)-.ALPHA.-((1-NAPHTHALENYLOXY)METHYL)-1-PIPERAZINEETHANOL DIHYDROCHLORIDE

Systematic Name

English

NAFTOPIDIL DIHYDROCHLORIDE, (±)-

Common Name

English

Code System Code Type Description

FDA UNII

6I80E37JBE