Delving into the Latest Updates on NXN-188 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

5-HT1B receptor x 5-HT1D receptor x eNOS

Mechanism

5-HT1B receptor agonists(Serotonin 1b (5-HT1b) receptor agonists), 5-HT1D receptor agonists(Serotonin 1d (5-HT1d) receptor agonists), eNOS inhibitors(Nitric-oxide synthase, endothelial inhibitors)

Therapeutic Areas

Nervous System Diseases

Active Indication-

Inactive Indication

Migraine With AuraMigraine Without Aura

Originator Organization

NeurAxon Pharma, Inc.

Active Organization-

Inactive Organization

NeurAxon Pharma, Inc.

Drug Highest PhasePendingPhase 2

First Approval Date-

Regulation-

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This is a a multi-center, randomized, double-blind, parallel group, and placebo controlled, two-arm study of a single oral dose of NXN-188 for the treatment of acute migraine headache without aura. Up to 120 migraineurs will be enrolled. Approximately 60 subjects having a headache history of migraine without aura will complete each of the two treatment arms to evaluate NXN-188 600 mg or placebo.

Start Date01 Jul 2009

Sponsor / Collaborator

NeurAxon Pharma, Inc.

NCT00920686 / CompletedPhase 2

A Phase 2 Study of the Safety and Effectiveness of a Single Oral Dose of NXN 188 for the Treatment of Moderate to Severe Migraine Headache With Aura

NXN-188 Dihydrochloride is being developed as an immediate release oral product for the treatment of acute migraine. This study is being conducted to evaluate NXN-188 in subjects with a migraine history of aura.

Start Date01 Jun 2009

Sponsor / Collaborator

NeurAxon Pharma, Inc.

NCT00877838 / Unknown statusPhase 2IIT

A Phase 2a Study of the Safety and Effectiveness of NXN-188 for the Acute Treatment of Migraine Attacks With Aura

The following study is being conducted to explore the safety and effectiveness of a new chemical entity called NXN-188 in subjects with a history of migraine with aura. In this study subjects will treat two attacks of migraine with aura during the aura phase - once with placebo and once with NXN-188.

Start Date01 May 2009

Sponsor / Collaborator

Danish Headache Center

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100 Clinical Results associated with NXN-188

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100 Translational Medicine associated with NXN-188

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100 Patents (Medical) associated with NXN-188

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6

Literatures (Medical) associated with NXN-188

01 Aug 2014·Expert Opinion on Investigational DrugsQ2 · MEDICINE

Drugs targeting nitric oxide synthase for migraine treatment

Q2 · MEDICINE

Review

Author: Della-Morte, David ; Barbanti, Piero ; Aurilia, Cinzia ; Fofi, Luisa ; Egeo, Gabriella

INTRODUCTIONAmple evidence that nitric oxide (NO) is a causative molecule in migraine has encouraged research to develop drugs that target the NO-cGMP cascade for migraine treatment. NO synthase (NOS) inhibition is an innovative therapeutic principle.AREAS COVEREDThis paper reviews the rationale underlying NOS inhibition in migraine treatment. It also provides a review on the efficacy and safety data for NOS inhibitors (nonselective NOS inhibitor L-N(G)-methyl-arginine hydrochloride [L-NMMA], selective inducible NOS [iNOS] inhibitors GW273629 and GW274150, combined neuronal NOS [nNOS] inhibitor and 5-HT1B/1D receptor agonist NXN-188) in acute or preventive migraine treatment.EXPERT OPINIONThe data highlighted herein, from four placebo-controlled trials and 1 open-labeled clinical trial using 4 different NOS inhibitors on a total of 705 patients, provide convincing efficacy data only for the nonselective NOS inhibitor L-NMMA. Unfortunately, this NOS inhibitor raises cardiovascular safety concerns and has an unfavorable pharmacokinetic profile. As experimental studies predicted, iNOS inhibitors are ineffective in migraine. Still, upcoming selective nNOS inhibitors are a hope for migraine treatment, with the nNOS isoform being most clearly involved in trigeminovascular transmission and central sensitization. Future studies should help to clarify whether NOS inhibition is equally fruitful in acute and preventive treatment. It should also clarify if nNOS inhibition holds promise as a therapeutic tool for the treatment of chronic migraine and other forms of headache.

01 Jan 2013·CephalalgiaQ2 · MEDICINE

NXN-188, a selective nNOS inhibitor and a 5-HT_1B/1D receptor agonist, inhibits CGRP release in preclinical migraine models

Q2 · MEDICINE

Article

Author: Andrews, John S ; Olesen, Jes ; Jansen-Olesen, Inger ; Gupta, Saurabh ; Bhatt, Deepak K

Background NXN-188 is a combined neuronal nitric oxide synthase (nNOS) inhibitor and 5-hydroxytryptamine 1B/1D (5-HT1B/1D) receptor agonist. Using preclinical models, we evaluated whether these two unique therapeutic principles have a synergistic effect in attenuating stimulated calcitonin gene-related peptide (CGRP) release, a marker of trigeminal activation. Methods We examined the effect of NXN-188 on: (1) KCl-, capsaicin- and resiniferatoxin (RTX)-induced immunoreactive CGRP (iCGRP) release from isolated preparation of rat dura mater, trigeminal ganglion (TG) and trigeminal nucleus caudalis (TNC); and (2) capsaicin- and electrical stimulation (ES)-induced middle meningeal artery (MMA) dilation in a rat closed-cranial window. Results NXN-188 inhibited: (1) KCl-stimulated iCGRP release from dura mater (% decrease mean ± SEM, lowest effective concentration) (35 ± 6%, 30 µM), TG (24 ± 11 %, 10 µM) and TNC (40 ± 8%, 10 µM); (2) capsaicin- and RTX-induced iCGRP release from dura mater; and (3) capsaicin- and ES-induced increase in dural artery diameter (32 ± 5%, 3 mg kg−1 intravenous (i.v.) and 36 ± 1%, 10 mg kg−1 i.v.). Conclusions NXN-188 inhibits CGRP release from migraine-relevant cephalic tissues. Its effect is most likely mediated via a combination of nNOS-inhibition and 5-HT1B/1D receptor agonism in dura mater while the mechanisms of action for inhibition of CGRP release from TG and TNC have to be investigated further.

01 Jan 2013·Scandinavian Journal of Pain

The nitric oxide synthase inhibitor and serotonin-receptor agonist NXN-188 during the aura phase of migraine with aura: A randomized, double-blind, placebo-controlled cross-over study

Article

Author: Tfelt-Hansen, Peer ; Guo, Song ; Hauge, Anne Werner ; Hougaard, Anders

AbstractBackground and aimsNXN-188 is a combined neuronal nitric oxide synthase (nNOS) inhibitor and 5HT-1B/1D receptor agonist which has previously shown efficacy in the acute treatment of migraine. Nitric oxide (NO) is involved in the pathogenesis of migraine pain and is formed after cortical spreading depression. Therefore NXN-188 could perhaps prevent the development of the headache phase in migraine with aura if taken during the aura. The aims of the present study were to evaluate the efficacy and safety of 600mg NXN-188 in the acute treatment of migraine when dosed during the aura.MethodsA single-centre, randomized, double-blind, placebo-controlled, two-way crossover trial. The study medication was taken during the aura and the patients kept a study diary for 48h post-dose.ResultsOf 615 patients screened, 50 patients were included in the study and randomized. Only 18 patients completed both treatments in compliance with the study procedures. 22% of patients reported freedom of headache at 2h after intake of NXN-188 compared with only 11% of patients after placebo.ConclusionsThe dual-action drug NXN-188 with 5HT-1B/1D agonism and nNOS inhibition, taken orally during the aura phase did not have a statistically substantial effect on migraine headache in this study. This study was limited by a high drop-out rate and small sample of included patients who were able to complete the cross-over protocol. Therefore, efficacy of the treatment cannot be refuted with certainty.ImplicationsThis study illustrates the difficulties of doing well controlled studies in migraine patients with aura. nNOS inhibition is expected to be effective mostly in the aura phase, i.e. the oral administration may have had too slow pharmacokinetics to have effect. Parenteral administration may overcome this obstacle. 5HT-1B/1D agonism is not effective when dosed during migraine aura. Repeated dosing of the NXN-188 during and immediately following the aura may have exploited more the dualaction. The high drop-out rate may be reduced in future studies by having the patients familiarize themselves with the study procedure by filling out the attack report form while treating one attack with their own medication before entering the trial. A parallel group comparison may be a more effective trial design for treatment during an aura.

100 Deals associated with NXN-188

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External Link

KEGG	Wiki	ATC	Drug Bank
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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Migraine Without Aura	Phase 2	US	NeurAxon Pharma, Inc.	01 Jul 2009
Migraine With Aura	Phase 2	DK	NeurAxon Pharma, Inc.	01 May 2009

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00920686 (CTgov)	Phase 2	Migraine With Aura	239	placebo (Placebo)	qajuvfpgzm(fayczoqwrf) = buuskjlhbb mtfbqwryld (rcnpmamyzm, fdhgywkuug - ufuloopypp) View more	-	11 Aug 2014
				NXN-188 (NXN-188)	qajuvfpgzm(fayczoqwrf) = odjgjquhcb mtfbqwryld (rcnpmamyzm, hqbzgwefru - pkwrkpylzo) View more
NCT00959751 (CTgov)	Phase 2	Migraine With Aura \| Migraine Without Aura	195	NXN-188 (NXN-188 600 mg)	rvazcrotaz(iaupwfdrhc) = upbmbjbkog vdnqlfnicq (rgzvorcchc, lxvltqyrma - mxwkkufgve) View more	-	11 Jul 2014
				Placebo (Placebo)	rvazcrotaz(iaupwfdrhc) = ebvigqqevk vdnqlfnicq (rgzvorcchc, drsrykrslt - xsduxjmtxk) View more