Delving into the Latest Updates on Dasotraline Hydrochloride with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Dasotraline

+ [4]

Target

DAT x NET x SERT

Mechanism

DAT antagonists(Dopamine transporter antagonists), NET inhibitors(Norepinephrine transporter inhibitors), SERT inhibitors(Serotonin transporter inhibitors)

Therapeutic Areas

Other Diseases

Active Indication-

Inactive Indication

Attention Deficit Disorder With HyperactivityBinge-Eating DisorderDepressive Disorder, Major

Originator Organization

Sumitomo Pharma Co., Ltd.

Active Organization-

Inactive Organization

Sumitomo Pharma America, Inc.

Drug Highest PhasePendingNDA/BLA

First Approval Date-

Regulation-

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Structure

Molecular FormulaC16H16Cl3N

InChIKeyYKXHIERZIRLOLD-DFIJPDEKSA-N

CAS Registry675126-08-6

View All Structures (2)

The use of first-line drugs in clinical practice for attention deficit hyperactivity disorder (ADHD) is limited by their adverse effects. Many novel monoamine reuptake inhibitors (MRIs) with better safety profiles and comparable efficacy are also being tried for ADHD. This network meta-analysis (NMA) has evaluated the efficacy and safety of MRIs in ADHD. The data was extracted from 31 relevant clinical trials after a literature search on MEDLINE/PubMed, Embase, Scopus, Cochrane databases, and clinical trial registries. Quality assessment was performed using the risk of bias assessment tool (RoB2) by Cochrane Collaboration, and the random-effects model was used to estimate the effect size. Standardised mean difference (SMD) and 95% credible interval(95%CrI) were reported for the reduction in ADHD rating scale score. Network geometry was visualised, and node splitting was done for the closed triangles. Meta-regression was done for the duration of therapy. PRISMA-NMA guidelines were followed in selecting, analyzing, and reporting findings. The drugs showing significant reduction on the ADHD rating scale as compared to placebo are bupropion (SMD: 0.33; 95%CrI: 0.60,-0.059), dasotraline(SMD: 0.49; 95%CrI: 0.82,-0.16), venlafaxine(SMD: 0.71; 95%CrI: 1.3,-0.15), viloxazine(SMD: 0.45; 95%CrI: 0.77,-0.12). Other drugs (centanafadine, duloxetine, edivoxetine, reboxetine, tipepidine, vortioxetine) were no better than placebo in reducing symptom severity of ADHD. The efficacy of none of the drugs was found to be significantly different as compared to methylphenidate. Among all, duloxetine (OR:15; 95%CrI:1.8130) showed significantly more treatment-emergent adverse events than methylphenidate. In conclusion, venlafaxine, viloxazine, and bupropion are the most efficacious MRIs for ADHD symptom reduction as compared to placebo with high certainty of evidence.

23 May 2024·Expert Opinion on Pharmacotherapy

The role of adrenergic neurotransmitter reuptake inhibitors in the ADHD armamentarium

Review

Author: Arnold, L. Eugene ; Ilipilla, Geeta

INTRODUCTIONAdrenergic neurotransmitter reuptake inhibitors are gaining attention in treatment for attention-deficit hyperactivity disorder (ADHD). Due to their effects on norepinephrine, dopamine, and serotonin neurotransmission, they benefit both ADHD and comorbid disorders and have some other advantages including longer duration of action and fewer adverse effects compared to stimulants. There is continued interest in these agents with novel mechanisms of action in treatment of ADHD.AREAS COVEREDThe authors conducted a PubMed literature search using the following key words: 'ADHD' AND 'adrenergic reuptake inhibitors' OR 'nonstimulants' OR 'atomoxetine' OR 'Viloxazine' OR 'Dasotraline' OR 'Centanafadine' OR 'PDC-1421' OR 'Reboxetine' OR 'Edivoxetine' OR 'Bupropion' OR 'Venlafaxine' OR 'Duloxetine.' They reviewed FDA fact sheets of available medications for safety/tolerability studies and reviewed published clinical studies of these medications for treatment of ADHD.EXPERT OPINIONAdrenergic neurotransmitter reuptake inhibitors fit the diverse needs of children and adolescents with ADHD with 1) poor tolerability to stimulants (e.g. due to growth suppression, insomnia, rebound irritability, co-morbid depression, anxiety and tic disorders, substance abuse or diversion concerns), 2) cardiac risks, and/or 3) need for extended duration of action. Their differences in receptor affinities and modulating effects support the unique benefits of individual agents.

01 Jun 2023·Neuroscience and biobehavioral reviews

The future of child and adolescent clinical psychopharmacology: A systematic review of phase 2, 3, or 4 randomized controlled trials of pharmacologic agents without regulatory approval or for unapproved indications.

Review

Author: Parellada, Mara ; Moreno, Carmen ; Wong, Ian C. K. ; Purper-Ouakil, Diane ; Vitiello, Benedetto ; Zuddas, Alessandro ; Santosh, Paramala ; Cortese, Samuele ; Zalsman, Gil ; Grunblatt, Edna ; Nagy, Peter ; Solmi, Marco ; Baeza, Immaculada ; Correll, Christoph U. ; Castro-Fornieles, Josefina ; Stringaris, Argyris ; Banaschewski, Tobias ; Hoejlund, Mikkel ; Apter, Alan ; Cohen, David ; Pagsberg, Anne Katrine ; Persico, Antonio M. ; Buitelaar, Jan ; Simonoff, Emily ; Stevanovic, Dejan ; Coghill, David ; Weizman, Abraham ; Roessner, Veit ; Arango, Celso ; McGinn, Katherine ; James, Anthony ; Wohlfarth, Tamar ; Jeppesen, Pia ; Walitza, Susanne ; Hoekstra, Pieter J.

We aimed to identify promising novel medications for child and adolescent mental health problems. We systematically searched https://clinicaltrials.gov/ and https://www.clinicaltrialsregister.eu/ (from 01/01/2010-08/23/2022) for phase 2 or 3 randomized controlled trials (RCTs) of medications without regulatory approval in the US, Europe or Asia, including also RCTs of dietary interventions/probiotics. Additionally, we searched phase 4 RCTs of agents targeting unlicensed indications for children/adolescents with mental health disorders. We retrieved 234 ongoing or completed RCTs, including 26 (11%) with positive findings on ≥ 1 primary outcome, 43 (18%) with negative/unavailable results on every primary outcome, and 165 (70%) without publicly available statistical results. The only two compounds with evidence of significant effects that were replicated in ≥ 1 additional RCT without any negative RCTs were dasotraline for attention-deficit/hyperactivity disorder, and carbetocin for hyperphagia in Prader-Willi syndrome. Among other strategies, targeting specific symptom dimensions in samples stratified based on clinical characteristics or established biomarkers may increase chances of success in future development programmes.

100 Deals associated with Dasotraline Hydrochloride

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External Link

KEGG	Wiki	ATC	Drug Bank
-	Dasotraline Hydrochloride	-	DB12305

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Binge-Eating Disorder	NDA/BLA	US	Sumitomo Pharma America, Inc.	11 Apr 2019
Depressive Disorder, Major	NDA/BLA	US	Sumitomo Pharma America, Inc.	01 Dec 2007
Attention Deficit Disorder With Hyperactivity	Phase 3	US	Sumitomo Pharma America, Inc.	01 Jun 2014

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03231800 (Pubmed) Manual	Phase 3	Attention Deficit Disorder With Hyperactivity	95	Dasotraline	(kxoktkmlsk) = fjvnuffqwy xabdycwyfk (ympphazmoy, 0.775)	Positive	20 Jan 2022
				placebo	(kxoktkmlsk) = cwppepwjfi xabdycwyfk (ympphazmoy, 0.773)
NCT02564588 (Pubmed) Manual	Phase 2/3	Binge-Eating Disorder	315	Dasotraline	kkquikngus(lrtqputsum) = nubyjncbda vfksemmmqi (ikfwsuzzyj, 0.17) View more	Positive	08 Sep 2020
				Placebo	(ogqwvvlnxj) = oactkznhsd abewqfnxiw (vkzvrjfqyh ) View more
NCT02684279 (CTgov)	Phase 3	Binge-Eating Disorder	533	Dasotraline	mzhqnlexwp(gtgorxpucb) = izhchergnv wpkiesixyk (iwuloyfqpg, vlbfdsufzy - nkgvlehcdh) View more	-	12 Aug 2020
NCT03107026 (CTgov)	Phase 3	Binge-Eating Disorder	491	Placebo (Placebo)	cfexxciajn(avvhwbejwd) = orbzgamhfb zlwqqrywgg (hzvitsnujs, lcfjhvolgk - egjnmbsamu) View more	-	13 Jul 2020
				dasotraline 4mg (Dasotraline 4mg)	cfexxciajn(avvhwbejwd) = bsnavjrjod zlwqqrywgg (hzvitsnujs, fhwkcrkbzd - bcaafmefnm) View more
NCT03231800 (CTgov)	Phase 3	Attention Deficit Disorder With Hyperactivity	95	Placebo (Placebo)	qoabezqmft(smgeddxupc) = cmbauxstyc eswttzquvc (knfjhhammt, hxycwaceby - kqktkyvkdd) View more	-	24 Jun 2020
				dasotraline (Dasotraline)	qoabezqmft(smgeddxupc) = xgabhjpbsz eswttzquvc (knfjhhammt, wmtduocpcc - jzwnxjzrnt) View more
NCT02734693 (CTgov)	Phase 3	Attention Deficit Disorder With Hyperactivity	132	Placebo (Placebo)	wocufjahpe(vleawdalay) = mlyvmkwqvh xvjzvvyohe (gydxqqjptu, yaapzvovct - qsfxuspttt) View more	-	27 Mar 2020
				dasotraline 4mg (Dasotraline 4mg)	wocufjahpe(vleawdalay) = bgwleauyko xvjzvvyohe (gydxqqjptu, gchkenouwj - aweibxsdpk) View more
NCT02457819 (CTgov)	Phase 3	Attention Deficit Disorder With Hyperactivity	237	Dasotraline	gtqjimpkvw(yrqnckgliu) = gkyspviqgz jqqpnifhkj (sekqjanmyi, rabziymltk - gxlsoobtxb) View more	-	18 Jan 2020
NCT02734693 (Pubmed) Manual	Phase 3	Attention Deficit Disorder With Hyperactivity	112	dasotraline	lasdkgosfq(zyugroozbh) = gmzdkskvjg rcdsmtjodd (awwtckhbtg )	Positive	01 Jan 2020
				Placebo	lasdkgosfq(zyugroozbh) = curlfkdsld rcdsmtjodd (awwtckhbtg )
NCT01692782 (CTgov)	Phase 2	Attention Deficit Disorder With Hyperactivity	341	SEP-225289 (SEP-225289 4mg)	itlhdanvxi(dmtkcmotrr) = mgwmiqashn dqmvobzjud (nxrhavqxni, mzfknewzzz - lygrntdpjx) View more	-	12 Jan 2015
				SEP-225289 (SEP-225289 8mg)	itlhdanvxi(dmtkcmotrr) = rfkbuvpcyp dqmvobzjud (nxrhavqxni, xaplpeoxkq - daikhyznoh) View more