In vitro pharmacological characterization of SPN-810M (molindone)

Yu, Chung-Ping; Gopalakrishnan, Gopakumar

doi:10.2147/jep.s180777

Cited by 6 publications

(4 citation statements)

References 35 publications

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“…Even molindone, while considered an older antipsychotic, has serotonin blocking actions similar to the new atypical antipsychotics. 28 As is true of brexpiprazole, many newer drugs that are effective in treating psychosis have effects that go far beyond blockade of the DA 2 receptor, which may explain the use of these drugs in ADHD. Brexpiprazole has partial agonist activity at the DA 2 receptor, plus actions at several serotonergic receptors as well as α noradrenergic.…”

Section: Discussionmentioning

confidence: 99%

“…All of the antipsychotic medications mentioned in the Introduction, which have been used with a stimulant, with the exception of molindone, are considered atypical antipsychotics with much more diverse neurochemical actions. Even molindone, while considered an older antipsychotic, has serotonin blocking actions similar to the new atypical antipsychotics 28 . As is true of brexpiprazole, many newer drugs that are effective in treating psychosis have effects that go far beyond blockade of the DA 2 receptor, which may explain the use of these drugs in ADHD.…”

Section: Discussionmentioning

confidence: 99%

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The Use of Brexpiprazole Combined With a Stimulant in Adults With Treatment-Resistant Attention-Deficit/Hyperactivity Disorder

Reimherr¹,

Gift²,

Steans³

et al. 2022

J Clin Psychopharmacol

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Background: This is the first controlled pharmacologic study in either adults or children with uncomplicated, treatment-resistant attention-deficit/ hyperactivity disorder (ADHD). This study augmented stimulant therapy with the atypical antipsychotic brexpiprazole. The Food and Drug Administration preapproved primary outcome measure (Conners' Adult ADHD Rating Scale [CAARS]) showed no drug-placebo differences. Often studies showing no efficacy on the prestudy, defined primary outcome variable go unpublished. While this is decried, publishing studies with equivocal results remains rare. This reanalysis highlights trends in secondary measures having implications for treatment and research regarding treatment resistant ADHD.Methods: Initially, 559 stimulant-naive and 174 prior stimulant nonresponders received methylphenidate osmotic-release oral system, dexmethylphenidate hydrochloride, lisdexamfetamine, or mixed amphetamine salts. After 5 weeks, 168 stimulant-naive patients and 68 prior stimulant nonresponders who failed treatment were randomized to brexpiprazole or placebo in a 2:1 ratio while the remaining were on the stimulant. Outcome was measured with the CAARS, Montgomery-Asberg Depression Rating Scale, Beck Depression Inventory, Clinical Global Impression, and the Wender-Reimherr Adult Attention Deficit Disorder Scale (WRAADDS). The WRAADDS contains 2 factors: attention and emotional dysregulation.Results: Stimulant-naive patients showed no improvement with adjunctive brexpiprazole. Prior stimulant nonresponders displayed no brexpiprazole effect on the CAARS, Montgomery-Asberg Depression Rating Scale, or Beck Depression Inventory. In contrast, the WRAADDS detected a trend in treatment benefit, primarily through emotional dysregulation symptoms. Adverse effects on brexpiprazole and placebo were equivalent.Conclusions: Brexpiprazole might be effective in ADHD adults who are nonresponders to 2 or more stimulants. Future trials in treatment-resistant ADHD should use a 1:1 randomization and use a measure of ADHD symptoms that includes emotional dysregulation.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The Use of Brexpiprazole Combined With a Stimulant in Adults With Treatment-Resistant Attention-Deficit/Hyperactivity Disorder

Reimherr¹,

Gift²,

Steans³

et al. 2022

J Clin Psychopharmacol

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“…While the exact mechanism of SPN-810 is unknown, emerging data suggest it functions as an antagonist of the dopamine receptors D 2S and D 2L and the serotonin receptor 5-HT 2B [90]. Although it remains to be confirmed, given these activities and the purported neuropathology of IA, it is suggested that SPN-810 may function by modulating the dopamine limbic pathway and its associated neural networks [15,90,91]. Further, the reduced incidence of EPS at therapeutic doses used for IA suggests that the potency of SPN-810 achieved at low doses is different from that of doses used for schizophrenia, which are highly associated with EPS [92].…”

Section: A Case Example Of An Ia Modulatormentioning

confidence: 99%

A proposed anti-maladaptive aggression agent classification: improving our approach to treating impulsive aggression

Robb

Schwabe

Ceresoli-Borroni

et al. 2019

Postgraduate Medicine

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Proper drug categorization enables clinicians to readily identify the agents most appropriate for patients in need. Currently, patients with maladaptive aggression do not all always fall into a single existing diagnostic or treatment category. Such is the case for those with impulsive aggression (IA). IA is an associated feature of numerous neuropsychiatric disorders, and can be described as eruptive, aggressive behavior or a 'short fuse'. Although agents from a broad spectrum of drug classes have been used to treat maladaptive aggression, few have been tested distinctly in patients with IA, and there is no drug specifically indicated by the US Food and Drug Administration (US FDA) for IA. Further, current treatments often fail to sufficiently treat IA symptomatology. These issues create an unclear and inadequate treatment path for patients. Here we will propose the establishment of a class of anti-maladaptive aggression agents to begin addressing this clinical issue. The development of such a class would unify the various drugs currently used to treat maladaptive aggression and streamline the treatment approach towards IA. As an important case example of the range of candidate drugs that could fit into a new anti-maladaptive aggression agent category, we will review an investigational IA pharmacotherapy. SPN-810 (extended-release molindone) is currently being investigated as a novel treatment for children with IA and ADHD. Based on these studies we will review how SPN-810 may be well suited for a new, anti-maladaptive aggression drug class and more precisely, a proposed subgroup of IA modulators. The goal of this review is to begin improving the identification of and therapeutic approach for maladaptive aggression as well as IA through more precise anti-maladaptive aggression agent categorization.

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“…In addition, its use is also considered in ADHD therapy (attention-deficit/hyperactivity disorder) [1][2][3]. The mechanism of molindone action assumes D 2S , D 2L , D 5 dopamine, and 5-HT 2B serotonin receptor antagonist activity and remains strictly in correlation with the dopamine hypothesis of schizophrenia [4][5][6][7][8][9]. It should also be noted that patients treated with molindone are exposed to the occurrence of side effects, for instance, tardive dyskinesia or akathisia, according to the commonly known mechanism of neuroleptics dopamine antagonistic potential [10][11][12].…”

Section: Introductionmentioning

confidence: 99%

Mimicking of Phase I Metabolism Reactions of Molindone by HLM and Photocatalytic Methods with the Use of UHPLC-MS/MS

et al. 2020

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Establishing the metabolism pathway of the drug undergoing the hepatic biotransformation pathway is one of the most important aspects in the preclinical discovery process since the presence of toxic or reactive metabolites may result in drug withdrawal from the market. In this study, we present the structural elucidation of six, not described yet, metabolites of an antipsychotic molecule: molindone. The elucidation of metabolites was supported with a novel photocatalytical approach with the use of WO3 and WS2 assisted photochemical reactions. An UHPLC-ESI-Q-TOF combined system was used for the registration of all obtained metabolite profiles as well as to record the high resolution fragmentation spectra of the observed transformation products. As a reference in the in vitro metabolism simulation method, the incubation with human liver microsomes was used. Chemometric comparison of the obtained profiles pointed out the use of the WO3 approach as being more convenient in the field of drug metabolism studies. Moreover, the photocatalysis was used in the direction of the main drug metabolite synthesis in order to further isolation and characterization.

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In vitro pharmacological characterization of SPN-810M (molindone)

Cited by 6 publications

References 35 publications

The Use of Brexpiprazole Combined With a Stimulant in Adults With Treatment-Resistant Attention-Deficit/Hyperactivity Disorder

The Use of Brexpiprazole Combined With a Stimulant in Adults With Treatment-Resistant Attention-Deficit/Hyperactivity Disorder

A proposed anti-maladaptive aggression agent classification: improving our approach to treating impulsive aggression

Mimicking of Phase I Metabolism Reactions of Molindone by HLM and Photocatalytic Methods with the Use of UHPLC-MS/MS

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