Delving into the Latest Updates on Molindone hydrochloride with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Molindone, Molindone XR, Molindone hydrochloride (USP)

+ [7]

Target

D2 receptor

Mechanism

D2 receptor antagonists(Dopamine D2 receptor antagonists)

Therapeutic Areas

Other Diseases

Active Indication

Schizophrenia

Inactive Indication

AggressionAttention Deficit Disorder With HyperactivityConduct Disorder

Originator Organization

Strides Pharma Global Pte Ltd.

Active Organization

Epic Pharma LLC

Inactive Organization

Supernus Pharmaceuticals, Inc.CHARTWELL RX SCIENCES LLC

Drug Highest PhaseApproved

First Approval Date

US (18 Jan 1974),

Schizophrenia

Regulation-

Login to view timeline

Structure

Molecular FormulaC16H24N2O2

InChIKeyKLPWJLBORRMFGK-UHFFFAOYSA-N

CAS Registry7416-34-4

View All Structures (2)

The purpose of this study is to evaluate the effect of 4-week SPN-810 treatment on brain functioning in patients aged 8-12 years with ADHD and associated feature of impulsive aggression (IA). This will be achieved using functional magnetic resonance imaging (fMRI) in conjunction with the point subtraction aggression paradigm (PSAP) Task, a behavioral aggression paradigm in which subjects are provoked by having money indirectly taken from them by a fictitious opponent, simulating an aggression response.

Start Date30 May 2019

Sponsor / Collaborator

Supernus Pharmaceuticals, Inc.

NCT03597503 / TerminatedPhase 3

Assessment of Efficacy and Safety of SPN-810 for the Treatment of Impulsive Aggression (IA) in Adolescent Subjects With Attention Deficit/Hyperactivity Disorder (ADHD) in Conjunction With Standard ADHD Treatment

The purpose of this study was to evaluate the effect of SPN-810 for the treatment of impulsive aggression (IA) in adolescents diagnosed with ADHD when taken in conjunction with standard ADHD treatment.

Start Date31 Jul 2018

Sponsor / Collaborator

Supernus Pharmaceuticals, Inc.

NCT02691182 / TerminatedPhase 3

Open-Label Extension Study to Evaluate the Long-Term Safety of Molindone Hydrochloride Extended-Release Tablets for the Treatment of Impulsive Aggression in Pediatric and Adolescent Subjects With Attention Deficit/Hyperactivity Disorder (ADHD) in Conjunction With Standard ADHD Treatment

Children between the ages of 6-12 years who are diagnosed with impulsive aggression comorbid with ADHD and have participated in the 810P301 or 810P302 study were invited to participate in this study. This was a Phase 3 open-label extension (OLE) study to collect long-term safety data on the use of SPN-810 in treating impulsive aggression in pediatric subjects with ADHD when taken in conjunction with standard ADHD treatment. After confirmation of eligibility, all subjects were treated with SPN-810. Subjects were given a choice to extend participation in this study every 6 months for up to 36 months.

Start Date01 Apr 2016

Sponsor / Collaborator

Supernus Pharmaceuticals, Inc.

100 Clinical Results associated with Molindone hydrochloride

Login to view more data

100 Translational Medicine associated with Molindone hydrochloride

Login to view more data

100 Patents (Medical) associated with Molindone hydrochloride

Login to view more data

25

Literatures (Medical) associated with Molindone hydrochloride

01 Sep 2021·Journal of Attention DisordersQ2 · MEDICINE

A Double-Blind, Randomized Study of Extended-Release Molindone for Impulsive Aggression in ADHD

Q2 · MEDICINE

Article

Author: Findling, Robert L. ; Liranso, Tesfaye ; Xu, Jiahong ; Schwabe, Stefan ; Adewole, Toyin ; Nasser, Azmi ; Ceresoli-Borroni, Gianpiera

Objective: To evaluate efficacy and safety of SPN-810 (extended-release molindone) in a Phase-2b, randomized, double-blind, placebo-controlled, dose-ranging study of children (6–12 years) with ADHD and persistent impulsive aggression (IA). Method: After lead-in, children were randomized to (a) placebo ( N = 31); (b) low-dose ( N = 29, 12/18 mg/day); (c) medium-dose ( N = 30, 24/36 mg/day); and (4) high-dose ( N = 31, 36/54 mg/day) groups. Treatment included ~2.5-week titration, 3-week maintenance, and 1-week tapering/conversion, alongside existing monotherapy (stimulants/nonstimulants) and behavioral therapy. The primary endpoint was change in Retrospective-Modified Overt Aggression Scale (R-MOAS) score at end of study, with safety monitored. Results: A total of 95 (78.5%) children completed the study. Aggression (R-MOAS) improved with low and medium doses (low dose: p = .031; medium dose: p = .024; high dose: p = .740). The most common adverse events were headache (10.0%), sedation (8.9%), and increased appetite (7.8%). Conclusion: These results suggest SPN-810 may be effective in reducing residual IA behaviors in children with ADHD. Research is still needed to support the benefit–risk profile of SPN-810 in pediatric populations.

13 Jun 2017·Toxicology Mechanisms and MethodsQ4 · MEDICINE

Toxicity assessment of molindone hydrochloride, a dopamine D2/D5 receptor antagonist in juvenile and adult rats

Q4 · MEDICINE

Article

Author: Gopalakrishnan, Gopa ; Krishna, Gopala ; Goel, Saryu

Neuroleptic drug molindone hydrochloride is a dopamine D2/D5 receptor antagonist and it is in late stage development for the treatment of impulsive aggression in children and adolescents who have attention deficient/hyperactivity disorder (ADHD). This new indication for this drug would expand the target population to include younger patients, and therefore, toxicity assessments in juvenile animals were undertaken in order to determine susceptibility differences, if any, between this age group and the adult rats. Adult rats were administered molindone by oral gavage for 13 weeks at dose levels of 0, 5, 20, or 60 mg/kg-bw/day. Juvenile rats were dosed for 8 weeks by oral gavage at dose levels of 0, 5, 25, 50, or 75 mg/kg-bw/day. Standard toxicological assessments were made using relevant study designs in consultation with FDA. Treatment-related elevation in serum cholesterol and triglycerides and decreases in glucose levels were observed in both the age groups. Organ weight changes included increases in liver, adrenal gland and seminal vesicles/prostate weights. Decreases in uterine weights were also observed in adult females exposed to the top two doses with sufficient exposure. In juveniles, sexual maturity parameters secondary to decreased body weights were observed, but, were reversed. In conclusion, the adverse effects noted in reproductive tissues of adults were attributed to hyperprolactinemia and these changes were not considered to be relevant to humans due to species differences in hormonal regulation of reproduction. On the whole, there were no remarkable differences in the toxicity profile of the drug between the two age groups.

01 May 2016·Environmental and Molecular MutagenesisQ3 · ENVIRONMENTAL SCIENCE & ECOLOGY

In vitro and in vivo genotoxicity assessment of the dopamine receptor antagonist molindone hydrochloride

Q3 · ENVIRONMENTAL SCIENCE & ECOLOGY

Article

Author: Gopalakrishnan, Gopa ; Krishna, Gopala ; Goel, Saryu

Molindone hydrochloride is a dihydroindolone neuroleptic with dopamine D2 and D5 receptor antagonist activity. As an integral component of its preclinical safety evaluation, molindone hydrochloride was evaluated in a series of in vitro and in vivo genetic toxicology assays. In the bacterial reverse gene mutation assays employing four Salmonella tester strains (TA98, TA100, TA1535, and TA1537) and the E. coli tester strain WP2uvrA, molindone hydrochloride was negative in all strains, except TA100, in which it induced a positive response (up to 3‐fold) in the presence of rat liver S9. With human S9, a small (2‐fold), but nonreproducible, increase in revertants was observed in TA100 at the highest concentration of molindone tested (5,000 µg/plate). The mutagenicity was completely abrogated by the addition of glutathione and UDP‐glucuronic acid to rat liver S9, suggesting detoxification of the mutagenic metabolite(s) by Phase II conjugation reactions, pathways commonly operational in humans. Molindone hydrochloride did not induce chromosomal aberrations in human lymphocyte cultures, did not elicit a positive response in a rat bone marrow micronucleus test for clastogencity/aneugenicity, and did not give a positive response in the rat liver comet assay for DNA damage. Collectively, the weight of evidence from these studies, combined with a large margin of safety and efficient detoxification through Phase II conjugation supports the interpretation that molindone hydrochloride does not pose a genotoxic risk to humans at the anticipated clinical dose levels. Environ. Mol. Mutagen. 57:288–298, 2016. © 2016 Wiley Periodicals, Inc.

100 Deals associated with Molindone hydrochloride

Login to view more data

External Link

KEGG	Wiki	ATC	Drug Bank
D00796	Molindone hydrochloride	N05AE02	DB01618

R&D Status

Approved

10 top approved records.

Login

to view more data

Indication	Country/Location	Organization	Date
Schizophrenia	US	Epic Pharma LLC	20 Mar 2015

Developing

10 top R&D records.

Login

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Aggression	Phase 2	US	Supernus Pharmaceuticals, Inc.	31 Jul 2018
Attention Deficit Disorder With Hyperactivity	Phase 2	US	Supernus Pharmaceuticals, Inc.	25 Jan 2016
Attention Deficit Disorder With Hyperactivity	Phase 2	US	Supernus Pharmaceuticals, Inc.	25 Jan 2016
Conduct Disorder	Phase 2	US	Supernus Pharmaceuticals, Inc.	01 Sep 2008

Login to view more data

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02691182 (CTgov)	Phase 3	Attention Deficit Disorder With Hyperactivity	491	SPN-810 (<18 mg SPN-810)	aekeryedzw(doljvdzzin) = ithfhuaurj tyntghlktb (ygughobywd, ehppmoeoqw - crxuyxmdbh) View more	-	16 May 2024
				SPN-810 (18 mg to < 24 mg SPN-810)	aekeryedzw(doljvdzzin) = bajaouxnld tyntghlktb (ygughobywd, jvrtayyllg - vyloiijxte) View more
NCT02618434 (CTgov)	Phase 3	Attention Deficit Disorder With Hyperactivity	297	Placebo (Placebo)	nhpajorius(hpoikkmdmz) = embrtrmbut qhdirijmkh (boglctzywv, pxbldhgmzs - kmapytjwiz) View more	-	18 Mar 2024
				SPN-810 (36 mg) (High Dose SPN-810 (36 mg))	nhpajorius(hpoikkmdmz) = pfencxxqgh qhdirijmkh (boglctzywv, hemojhnklz - gcwjciglov) View more
NCT03597503 (CTgov)	Phase 3	Aggression \| Attention Deficit Disorder With Hyperactivity	41	Placebo (Placebo)	mmzbamzncr(aeqsvhhgyg) = xrbojnntnl rcqexyvltm (ayplqzptbn, ukdyfzlubi - rsqspxddvs) View more	-	20 Feb 2024
				SPN-810 (Flexible Dose of SPN-810)	mmzbamzncr(aeqsvhhgyg) = gdmgmjhaeh rcqexyvltm (ayplqzptbn, rbvwxwlrke - nndfivgpcl) View more
NCT02618408 (CTgov)	Phase 3	Attention Deficit Disorder With Hyperactivity	333	Placebo (Placebo)	ngzhninebt(lgekuyniap) = mvdvpnedvk sulnmihase (tgcuaclwkv, nsygoqmxgj - phmuwbkdvb) View more	-	01 Nov 2022
				SPN-810 (18 mg) (Low Dose SPN-810 (18 mg))	ngzhninebt(lgekuyniap) = yepbntkhfp sulnmihase (tgcuaclwkv, ftblegmyij - bbuoxbbiiy) View more
NCT00053703 (TEOSS, CTgov)	Phase 4	Schizophrenia	116	Olanzapine (enrollment closed in this treatment) (Olanzapine)	igqoutjcig(ebuiupmhdb) = ndupqckste dkdvpqqtjf (zotgyqlbzf, kjvggagiyd - fspgafyhbf) View more	-	26 Mar 2014
				risperidone (Risperidone)	igqoutjcig(ebuiupmhdb) = ozjbgmmusy dkdvpqqtjf (zotgyqlbzf, hbvlepzneg - hxszlixssd) View more