Delving into the Latest Updates on Nepadutant with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

NK2R

Mechanism

NK2R antagonists(Neurokinin 2 receptor antagonists)

Therapeutic Areas

Congenital DisordersDigestive System Disorders

Active Indication-

Inactive Indication

ColicFeeding intoleranceGastrointestinal Diseases

Originator Organization

A. Menarini Industrie Farmaceutiche Riunite SRL

Active Organization-

Inactive Organization

A. Menarini Industrie Farmaceutiche Riunite SRL

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

Login to view timeline

Structure

Molecular FormulaC45H58N10O13

InChIKeyNGCNKEZHGRXHNL-WVWQGFTISA-N

CAS Registry183747-35-5

Gene Sequence

Sequence Code 16642011

Source: *****

The present pilot study is aimed to obtain preliminary data on the effect of three ascending oral dose levels of nepadutant on the relief of symptoms associated with feeding intolerance. In addition, the assessment of drug exposure (PK assessment) will provide additional information on the dose-effect relationship, thus supporting the dose selection and dosing schedule in the future studies.

Start Date01 Aug 2011

Sponsor / Collaborator

A. Menarini Industrie Farmaceutiche Riunite SRL

NCT01309009 / WithdrawnPhase 2

Double-blind, Randomised, Placebo-controlled, Parallel Group Pilot Study to Evaluate the Efficacy and Safety of Oral Administration of Nepadutant in Infant Colic Babies Not Responder to Conventional Treatments

This phase IIa study is designed as a multi-centre, single country, randomised, double-blind, placebo controlled study in three parallel groups, with the aim to evaluate the efficacy and safety of Nepadutant given at two oral doses once daily for seven days in comparison to placebo in the treatment of infantile colic.

Start Date01 Feb 2011

Sponsor / Collaborator

A. Menarini Industrie Farmaceutiche Riunite SRL

EUCTR2010-022706-41-IT / Not yet recruitingNot Applicable

Double-blind, randomised, placebo-controlled, parallel group pilot study to evaluate the efficacy and safety of oral administration of Nepadutant in infant colic babies not responder to conventional treatments - NOCRY-a

Start Date08 Nov 2010

Sponsor / Collaborator

Menarini Ricerche SpA

100 Clinical Results associated with Nepadutant

Login to view more data

100 Translational Medicine associated with Nepadutant

Login to view more data

100 Patents (Medical) associated with Nepadutant

Login to view more data

65

Literatures (Medical) associated with Nepadutant

01 Feb 2013·European Journal of PharmacologyQ3 · MEDICINE

Characterization of ibodutant at NK2 receptor in human colon

Q3 · MEDICINE

Article

Author: Catalani, Claudio ; Maggi, Carlo Alberto ; Santicioli, Paolo ; Bechi, Paolo ; Riccadonna, Sara ; Ringressi, Maria Novella ; Meini, Stefania ; Giuliani, Sandro

We have characterized the pharmacological profile of the nonpeptide tachykinin NK2 receptor antagonist ibodutant (MEN15596) through radioligand binding and contractility assays in the human colon smooth muscle. The antagonist affinity of ibodutant was evaluated through concentration-dependent inhibition curves at the [(125)I]NKA specific binding by using membranes prepared from human colon smooth muscle. In this assay the affinity of ibodutant (pKi 9.9) was compared to that of other two selective NK2 receptor antagonists, nepadutant (pKi 8.4) and saredutant (pKi 9.2). The antagonist potency of ibodutant was evaluated towards the [βAla(8)]NKA(4-10)-mediated contractions of human colon smooth muscle strips. In this assay ibodutant (3, 10, 30 and 100 nM) induced a concentration-dependent rightward shift of the [βAla(8)]NKA(4-10) concentration-response curves without depressing the maximal contractile effect. The analysis of the curves yielded a Schild-plot linear regression with a slope not different from unity (1.02), thus indicating a surmountable antagonist behavior. The calculated apparent antagonist potency as pKB value was 9.1. No sex related differences were observed in NK2 receptor pharmacology for [βAla(8)]NKA(4-10) or ibodutant in colonic strips obtained from male or female patients. Reversibility experiments of tachykinin NK2 receptor blockade indicated that the inhibition of the agonist-induced contractions in preparations pre-exposed to ibodutant, and afterwards subjected to repeated washing cycles remained almost constant showing no sign of recovery during the 3h observation period. Overall, the present study indicates ibodutant as a potent tachykinin NK2 receptor antagonist in the human colon tissue, also endowed with a persistent duration of action.

01 Jun 2010·NeuropeptidesQ3 · MEDICINE

Influence of tachykinin NK2 receptors on intestinal sensitivity and motility in newborn rats

Q3 · MEDICINE

Article

Author: Tramontana, M. ; Evangelista, S. ; Girod, V. ; Maggi, C. A. ; Giuliani, S. ; Manzini, S. ; Robelet, S.

The effect of tachykinin neurokinin NK(2) receptors activation on intestinal propulsion and colorectal sensitivity was studied in 7-15 days old newborn rats. In a first set of experiments investigating the intestinal transit, the selective NK(2) receptor agonist, [betaAla(8)]NKA-(4-10) was used. It produced an increase of the small intestinal transit measured by charcoal test of 54%, that was inhibited in a dose-dependent manner by nepadutant ([N(4)-(2-acetamido-2-deoxy-beta-D-glucopyranosyl)-L-asparaginyl-L-aspartyl-L-tryptophyl-L-phenylalanyl-L-2,3-diaminopropionyl-L-leucyl]-C-4.2-N-3.5-lactam-C-1.6-N-2.1-lactam), a known selective NK(2) receptor antagonist, orally administered 2-48 h before the challenge with the NK(2) receptor agonist. Nepadutant did not affect the basal intestinal propulsion and showed a good oral bioavailability and long duration of action. In another set of experiments investigating visceral sensitivity, a fixed distension volume of a balloon inserted intrarectally in 14-15 days old newborns rats produced abdominal contractions (AC) that were increased after colonic application of acetic acid (50 microl, 0.5%). In this latter condition nepadutant, at 0.5 and 2.5 mg/kg p.o., significantly reduced the resulting AC. In control rats, untreated with acetic acid, nepadutant did not affect AC evoked by colorectal distension. These findings show for the first time two models to assess intestinal motility and visceral sensitivity in newborn rats and indicate nepadutant as a valuable tool to assess the role of NK(2) receptors in the intestinal propulsive and nociceptive activity in infants.

01 Oct 2009·Therapeutic Advances in Respiratory DiseaseQ3 · MEDICINE

The effect of the tachykinin NK2 receptor antagonist MEN11420 (nepadutant) on neurokinin A-induced bronchoconstriction in asthmatics

Q3 · MEDICINE

ArticleOA

Author: Pauwels, Romain ; Van De Velde, Veerle ; Schelfhout, Venessa ; Maggi, Carlo ; Joos, Guy

Objective: We previously reported that the nonpeptide tachykinin NK2 receptor antagonist SR48968 (saredutant) significantly inhibits neurokinin A-induced bronchoconstriction in patients with asthma. MEN11420 (nepadutant) is a bicyclic peptide tachykinin NK2 receptor antagonist. The aim of the trial was to examine the effect of nepadutant on neurokinin A-induced bronchoconstriction in man. Methods: 12 patients with stable, mild to moderate asthma participated in a double-blind, placebo-controlled crossover trial and received, with intervals of 1 week, MEN11420 2 mg, MEN11420 8 mg and placebo (i.v.). Increasing concentrations of NKA (10-9 to 10-6 moles/ml) were inhaled immediately after (d1) and 24 hours after (d2) administration of treatment. Results: On d1 both MEN11420 2 and 8 mg shifted the dose response curve for neurokinin A to the right (log PC20 FEV1 neurokinin A [moles/ml]; mean± SEM -6.38±0.26 after 2 mg, -6.11±0.23 after 8 mg, versus -6.95±0.27 after placebo]. On d2 MEN11420 had no effect on neurokinin A-induced bronchoconstriction. Conclusion: In conclusion, the tachykinin NK2 receptor antagonist nepadutant significantly inhibits bronchoconstriction induced by neurokinin A in patients with asthma.

100 Deals associated with Nepadutant

Login to view more data

External Link

KEGG	Wiki	ATC	Drug Bank
-	Nepadutant	-	DB12538

R&D Status

10 top R&D records.

Login

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Feeding intolerance	Phase 2	US	A. Menarini Industrie Farmaceutiche Riunite SRL	01 Aug 2011
Colic	Phase 2	SE	A. Menarini Industrie Farmaceutiche Riunite SRL	01 Nov 2010
Colic	Phase 2	RU	A. Menarini Industrie Farmaceutiche Riunite SRL	01 Nov 2010
Colic	Phase 2	PL	A. Menarini Industrie Farmaceutiche Riunite SRL	01 Nov 2010
Colic	Phase 2	PL	A. Menarini Industrie Farmaceutiche Riunite SRL	01 Nov 2010
Colic	Phase 2	DE	A. Menarini Industrie Farmaceutiche Riunite SRL	01 Nov 2010
Colic	Phase 2	RU	A. Menarini Industrie Farmaceutiche Riunite SRL	01 Nov 2010
Colic	Phase 2	SE	A. Menarini Industrie Farmaceutiche Riunite SRL	01 Nov 2010
Colic	Phase 2	DE	A. Menarini Industrie Farmaceutiche Riunite SRL	01 Nov 2010
Gastrointestinal Diseases	Phase 2	US	A. Menarini Industrie Farmaceutiche Riunite SRL	01 Mar 2008

Login to view more data

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01258153 (no-cry, CTgov)	Phase 2	Colic	115	Nepadutant oral solution (Nepadutant Low Dose)	bwqvuettht(aloahqnkui) = rwrqbjeyvc wpwgruaedq (bnhcjhyqer, zuedkdjupg - gevmkmarmo) View more	-	10 Jun 2015
				Nepadutant oral solution (Nepadutant High Dose)	bwqvuettht(aloahqnkui) = wjpqxnwujx wpwgruaedq (bnhcjhyqer, lalcjfevcf - rykpykteue) View more
NCT00655083 (of Nepadutant in Infants \| Oral absorption, CTgov)	Phase 1	Colic \| Gastrointestinal Diseases	21	Nepadutant (Nepadutant 0.1 mg/kg)	wywzofttoy(xgmihbfeep) = ozfdutkqhn qdggglmcpy (scgtibkbjf, xboafqbppm - mikvsqpjdu) View more	-	25 Aug 2010
				Nepadutant (Nepadutant 0.5 mg/kg)	wywzofttoy(xgmihbfeep) = ysoriboddx qdggglmcpy (scgtibkbjf, kyhzqgjwgd - ycwgtbkmjf) View more