NALFURAFINE

Possibly Marketed Outside US

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C28H32N2O5
Molecular Weight	476.5641
Optical Activity	UNSPECIFIED
Defined Stereocenters	5 / 5
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

SMILES

CN([C@@H]1CC[C@@]2(O)[C@H]3CC4=CC=C(O)C5=C4[C@@]2(CCN3CC6CC6)[C@H]1O5)C(=O)\C=C\C7=COC=C7

InChI

InChIKey=XGZZHZMWIXFATA-UEZBDDGYSA-N

InChI=1S/C28H32N2O5/c1-29(23(32)7-4-18-9-13-34-16-18)20-8-10-28(33)22-14-19-5-6-21(31)25-24(19)27(28,26(20)35-25)11-12-30(22)15-17-2-3-17/h4-7,9,13,16-17,20,22,26,31,33H,2-3,8,10-12,14-15H2,1H3/b7-4+/t20-,22-,26+,27+,28-/m1/s1

HIDE SMILES / InChI

Molecular Formula	C28H32N2O5
Molecular Weight	476.5641
Charge	0
Count	MOL RATIO 1 MOL RATIO (average)

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	5 / 5
E/Z Centers	1
Optical Activity	UNSPECIFIED

Description

Nalfurafine, an opioid κ-selective agonist, has been officially approved for resistant pruritus in HD patients on the basis of a well-evidenced clinical trial in Japan. Nalfurafine hydrochloride is a potent and selective agonist for mouse, rat, guinea pig, and human κ-opioid receptors without significant activity on µ- and δ-opioid receptors. Nalfurafine hydrochloride (2.5 and 5 ug/day) has been proven to be safe and effective for the treatment of HD patients with uremic pruritus resistant to antihistamines.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Kappa opioid receptor 115	Agonist 2,752		25.0 pM [EC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Pruritus in hemodialysis patients 2	Primary		Approved 8,583	REMITCH

C_max

Value	Dose	Analyte	Population
12.67 pg/mL	10 μg single, oral	NALFURAFINE plasma	Homo sapiens
13.68 pg/mL	10 μg single, oral	NALFURAFINE plasma	Homo sapiens
209.37 pg/mL	30 μg single, intravenous	NALFURAFINE plasma	Homo sapiens
27.85 pg/mL	30 μg single, oral	NALFURAFINE plasma	Homo sapiens
19.1 pg/mL	10 μg single, oral	NALFURAFINE plasma	Homo sapiens
40.1 pg/mL	20 μg single, oral	NALFURAFINE plasma	Homo sapiens
90.3 pg/mL	40 μg single, oral	NALFURAFINE plasma	Homo sapiens
9.52 pg/mL	10 μg 1 times / day multiple, oral	NALFURAFINE plasma	Homo sapiens
9.68 pg/mL	10 μg 1 times / day multiple, oral	NALFURAFINE plasma	Homo sapiens
28.8 pg/mL	20 μg 1 times / day multiple, oral	NALFURAFINE plasma	Homo sapiens
33.8 pg/mL	20 μg 1 times / day multiple, oral	NALFURAFINE plasma	Homo sapiens
3.15 pg/mL	2.5 μg 1 times / day multiple, oral	NALFURAFINE plasma	Homo sapiens
5.7 pg/mL	2.5 μg 1 times / day multiple, oral	NALFURAFINE plasma	Homo sapiens
6.51 pg/mL	5 μg 1 times / day multiple, oral	NALFURAFINE plasma	Homo sapiens
10.25 pg/mL	5 μg 1 times / day multiple, oral	NALFURAFINE plasma	Homo sapiens
3.63 pg/mL	2.5 μg single, oral	NALFURAFINE plasma	Homo sapiens
6.76 pg/mL	5 μg single, oral	NALFURAFINE plasma	Homo sapiens

AUC

Value	Dose	Analyte	Population
114.46 pg × h/mL	10 μg single, oral	NALFURAFINE plasma	Homo sapiens
126.03 pg × h/mL	10 μg single, oral	NALFURAFINE plasma	Homo sapiens
666.03 pg × h/mL	30 μg single, intravenous	NALFURAFINE plasma	Homo sapiens
387.45 pg × h/mL	30 μg single, oral	NALFURAFINE plasma	Homo sapiens
297 pg × h/mL	10 μg single, oral	NALFURAFINE plasma	Homo sapiens
604 pg × h/mL	20 μg single, oral	NALFURAFINE plasma	Homo sapiens
967 pg × h/mL	40 μg single, oral	NALFURAFINE plasma	Homo sapiens
73.9 pg × h/mL	10 μg 1 times / day multiple, oral	NALFURAFINE plasma	Homo sapiens
66.1 pg × h/mL	10 μg 1 times / day multiple, oral	NALFURAFINE plasma	Homo sapiens
324 pg × h/mL	20 μg 1 times / day multiple, oral	NALFURAFINE plasma	Homo sapiens
436 pg × h/mL	20 μg 1 times / day multiple, oral	NALFURAFINE plasma	Homo sapiens
66.26 pg × h/mL	2.5 μg 1 times / day multiple, oral	NALFURAFINE plasma	Homo sapiens
210.25 pg × h/mL	2.5 μg 1 times / day multiple, oral	NALFURAFINE plasma	Homo sapiens
120.59 pg × h/mL	5 μg 1 times / day multiple, oral	NALFURAFINE plasma	Homo sapiens
358.86 pg × h/mL	5 μg 1 times / day multiple, oral	NALFURAFINE plasma	Homo sapiens
34.58 pg × h/mL	2.5 μg single, oral	NALFURAFINE plasma	Homo sapiens
58.06 pg × h/mL	5 μg single, oral	NALFURAFINE plasma	Homo sapiens

T_1/2

Value	Dose	Analyte	Population
5.99 h	10 μg single, oral	NALFURAFINE plasma	Homo sapiens
5.9 h	10 μg single, oral	NALFURAFINE plasma	Homo sapiens
7.93 h	30 μg single, intravenous	NALFURAFINE plasma	Homo sapiens
8.27 h	30 μg single, oral	NALFURAFINE plasma	Homo sapiens
9.75 h	10 μg single, oral	NALFURAFINE plasma	Homo sapiens
10.1 h	20 μg single, oral	NALFURAFINE plasma	Homo sapiens
10.5 h	40 μg single, oral	NALFURAFINE plasma	Homo sapiens
5.78 h	10 μg 1 times / day multiple, oral	NALFURAFINE plasma	Homo sapiens
5.77 h	10 μg 1 times / day multiple, oral	NALFURAFINE plasma	Homo sapiens
9.08 h	20 μg 1 times / day multiple, oral	NALFURAFINE plasma	Homo sapiens
9.6 h	20 μg 1 times / day multiple, oral	NALFURAFINE plasma	Homo sapiens
14.21 h	2.5 μg 1 times / day multiple, oral	NALFURAFINE plasma	Homo sapiens
25.33 h	2.5 μg 1 times / day multiple, oral	NALFURAFINE plasma	Homo sapiens
14.03 h	5 μg 1 times / day multiple, oral	NALFURAFINE plasma	Homo sapiens
28.34 h	5 μg 1 times / day multiple, oral	NALFURAFINE plasma	Homo sapiens
5.37 h	2.5 μg single, oral	NALFURAFINE plasma	Homo sapiens
6.61 h	5 μg single, oral	NALFURAFINE plasma	Homo sapiens

F_unbound

Value	Dose	Co-administered	Analyte	Population
23.7%			NALFURAFINE plasma	Homo sapiens

Doses

Show entries

Dose	Population	Adverse events
5 ug 1 times / day multiple, oral Recommended	unhealthy, ADULT	Disc. AE: Insomnia...
5 ug 3 times / week multiple, intravenous Recommended	unhealthy, ADULT	Disc. AE: Electrocardiogram abnormal, Myasthenia gravis...

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AEs

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AE	Significance	Dose	Population
Insomnia	1.75% Disc. AE	5 ug 1 times / day multiple, oral Recommended	unhealthy, ADULT
Electrocardiogram abnormal	Disc. AE	5 ug 3 times / week multiple, intravenous Recommended	unhealthy, ADULT
Fatigue	Disc. AE	5 ug 3 times / week multiple, intravenous Recommended	unhealthy, ADULT
Headache	Disc. AE	5 ug 3 times / week multiple, intravenous Recommended	unhealthy, ADULT
Hyperhidrosis	Disc. AE	5 ug 3 times / week multiple, intravenous Recommended	unhealthy, ADULT

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PubMed

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Title	Date	PubMed
Nalfurafine, a kappa opioid receptor agonist, inhibits scratching behavior secondary to cholestasis induced by chronic ethynylestradiol injections in rats.	2006 Sep	16919318

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Patents

Sample Use Guides

In Vivo Use Guide

The usual oral dosage for adults is 2.5 ug of nalfurafine hydrochloride, once a day, after supper or before sleep. The dosage may be adjusted according to symptoms provided that it does not exceed 5 ug once a day.

Route of Administration: Oral

In Vitro Use Guide

Nalfurafine hydrochloride inhibited the electrically-induced contraction of mouse vas deferens with the IC50 of 0.080 nmol/L and 0.12 nmol/L in two independent experiments in vitro.

Substance Class	Chemical
Record UNII	XC41AVD567
Record Status	`Validated (UNII)`
Record Version

Show entries

Name

Type

Language

NALFURAFINE

Official Name

English

MT-9938

Preferred Name

English

nalfurafine [INN]

Common Name

English

NALFURAFINE [MI]

Common Name

English

2-PROPENAMIDE, N-((5.ALPHA.,6.BETA.)-17-(CYCLOPROPYLMETHYL)-4,5-EPOXY-3,14-DIHYDROXYMORPHINAN-6-YL)-3-(3-FURANYL)-N-METHYL-, (2E)-

Systematic Name

English

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Classification Tree

Code System

Code

Agent Affecting Nervous System

NCI_THESAURUS

C67413

Other therapeutic products

WHO-VATC

QV03AX02

Other therapeutic products

WHO-ATC

V03AX02

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Code System

Code

Type

Description

EVMPD

SUB25222

PRIMARY

DRUG CENTRAL

4673

PRIMARY

INN

8209

PRIMARY

PUBCHEM

6445230

PRIMARY

CAS

152657-84-6

PRIMARY

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Related Record

Type

Details


					25CC4N0P8J

NALFURAFINE HYDROCHLORIDE

SALT/SOLVATE -> PARENT

Amount:


					2BJ58BX78W

KAPPA-TYPE OPIOID RECEPTOR

TARGET -> AGONIST

Amount:

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Related Record

Type

Details


					XC41AVD567

NALFURAFINE

ACTIVE MOIETY

Amount:

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SMILES

InChI

Originator

Approval Year

Targets

Conditions

Cmax

AUC

T1/2

Funbound

Doses

AEs

PubMed

Patents

Sample Use Guides

C_max

T_1/2

F_unbound