Effects of molindone: A Synthesis of Findings from 20 Studies

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Original Abstract of the Article

Main Research Findings

Several studies have shown that the effects of molindone depend on the dosage and duration of administration. A low dose (2.5 mg/kg) produced effects typical of DA receptor blockade, such as activation of synaptosomal tyrosine hydroxylase, increased DA metabolite levels, and unchanged DA levels. 6 A high dose (40 mg/kg) produced opposite effects, such as decreased tyrosine hydroxylase activity and metabolite concentrations, and elevated DA levels. 6 An intermediate dose of 10 mg/kg elicited intermediate effects. 6 These atypical effects of both higher doses were long-lasting (less than 72 hours). 6 Molindone at doses of 10 or 40 mg/kg, but not 2.5 mg/kg, selectively, irreversibly, and dose-dependently inhibited type A monoamine oxidase. 6 This inhibition appeared to be due to a metabolite, as the drug itself inhibited monoamine oxidase (reversibly) only at high concentrations (less than or equal to 10-4 M). 6 The previously unsuspected inhibition of monoamine oxidase by molindone provided a consistent mechanistic interpretation of the differential dose- and time-dependent effects of the drug on dopaminergic neuronal activity. 6 This mechanism may also serve to explain the reported efficacy of molindone in animal tests for antidepressant activity as well as its inability to produce increased DA receptor binding after chronic treatment. 6

Benefits and Risks

Benefit Summary

Molindone may be beneficial in treating impulsive aggression (IA) in patients with attention-deficit/hyperactivity disorder (ADHD). 17 It may also have antidepressant effects due to its inhibition of monoamine oxidase. 6

Risk Summary

Molindone may have adverse effects on dopamine neuron activity at high doses. 6 Side effects such as weight gain and sedation have also been reported. 19

Comparison between Studies

Commonalities between Studies

Multiple studies have shown that molindone affects dopamine neuron activity. 6 8 7 However, its effects differ depending on the dosage and duration of administration. 6 Additionally, several studies have reported that molindone inhibits monoamine oxidase. 6 5

Differences between Studies

Various research methods have been used to evaluate the effects of molindone. For example, some studies have measured dopamine levels in the brains of rats, 6 while others have examined the behavior of pigeons, 2 or conducted studies on humans with mental illnesses. These studies have yielded different results regarding the effects and side effects of molindone.

Consistency and Contradictions in Results

The effects of molindone vary significantly depending on factors such as dosage, duration, and individual differences, making it difficult to fully understand its effects. In particular, at high doses, it may have adverse effects on dopamine neuron activity, while at low doses, it may act as a DA receptor blocker. 6 Further research is necessary to explain these contradictory results.

Points to Note Regarding Applications in Real Life

Because the effects of molindone vary significantly depending on factors such as dosage, duration, and individual differences, it is crucial to select the appropriate dosage and administration method. 6 Molindone may also cause side effects such as weight gain and sedation. 19 Therefore, it is essential to use it as directed by a physician.

Limitations of Current Research

Research on the effects of molindone is still insufficient, particularly in humans. Long-term safety and efficacy data are limited, and further research is needed on factors that may affect molindone's effects, such as age, gender, genotype, and co-administered medications.

Future Research Directions

To gain a deeper understanding of the effects of molindone, long-term studies on humans are required. It is essential to examine the effects of various dosages, administration methods, and co-administered medications. Identifying the genes and proteins that may influence the effects of molindone could lead to personalized medication.

Conclusion

The effects of molindone depend on the dosage and duration of administration. 6 At low doses, it may act as a DA receptor blocker and have beneficial effects in treating impulsive aggression (IA) in patients with attention-deficit/hyperactivity disorder (ADHD). 17 However, at high doses, it may have adverse effects on dopamine neuron activity. 6 Side effects such as weight gain and sedation have also been reported. 19 When considering the use of molindone, it is essential to carefully evaluate these risks and benefits.

Literature analysis of 20 papers
Positive Content
16
Neutral Content
1
Negative Content
3
Article Type
1
3
3
4
20
1.

Effects of amantadine on modification of dopamine dependent behaviours by molindone.

Author: DhawareB S, BalsaraJ J, NandalN V, ChandorkarA G

Parkinson's treatment

Amantadine, a dopamine agonist, can antagonize or even reverse the neuroleptic-induced dopaminergic behaviors in rats, suggesting its potential as a treatment for dopamine-dependent conditions.

Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

2.

Neuroleptics and learning: effects of haloperidol, molindone, mesoridazine and thioridazine on the behavior of pigeons under a repeated acquisition procedure.

Author: PolingA, ClearyJ, BerensK, ThompsonT

Reduce responding rate
Increase error rates

Haloperidol was the least disruptive of four neuroleptics on the behavior of pigeons exposed to a repeated acquisition procedure.

Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, U.S. Gov't, P.H.S.Research funding provided by the Public Health Service (PHS).

Language : English

3.

A comparison of masking effects of haloperidol versus molindone in tardive dyskinesia.

Author: GlazerW M, HafezH

Mask tardive dyskinesia
No significant side effects

Haloperidol masked the effects of tardive dyskinesia more effectively than molindone.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
Research Support, U.S. Gov't, P.H.S.Research funding provided by the Public Health Service (PHS).

Language : English

4.

Molindone: effects in pigeons responding under conditional discrimination tasks.

Author: PickerM J, ClearyJ P, BerensK, OlivetoA H, DykstraL A

Impairs learning

Molindone, an atypical neuroleptic drug, impaired performance in tasks involving working memory, but not those requiring immediate memory. This suggests a specific effect on cognitive functions related to delay.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, U.S. Gov't, P.H.S.Research funding provided by the Public Health Service (PHS).

Language : English

5.

Selective effects of buspirone and molindone on dopamine metabolism and function in the striatum and frontal cortex of the rat.

Author: McMillenB A, McDonaldC C

Reverses catalepsy
Treats motor disorders

Dopamine autoreceptors were found to be absent in the frontal cortex, while present in the striatum. Buspirone, a non-benzodiazepine anti-anxiety drug, reversed catalepsy by enhancing dopamine release, suggesting potential for treating extrapyramidal motor disorders.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, U.S. Gov't, P.H.S.Research funding provided by the Public Health Service (PHS).

Language : English

7.

Effects of molindone and fluphenazine on the brain concentration of some phenolic and catecholic amines in the mouse and the rat.

Author: JuorioA V

Molindone acted as a blocker or partial agonist of dopamine receptors, affecting tyramine levels and dopamine metabolism.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

8.

Effects of molindone on central dopaminergic neuronal activity and metabolism: similarity to other neuroleptics.

Author: BunneyB S, RothR H, AghajanianG K

Reverse DA neuron depression

Molindone, an antipsychotic drug, was found to reverse d-amphetamine and apomorphine induced depression of dopaminergic (DA) neurons and to block apomorphine induced depression of these cells. It also increased dopamine synthesis and dihydroxyphenylactic acid levels in the striatum and olfactory tubercles.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, U.S. Gov't, Non-P.H.S.Research funding provided by US government agencies other than the Public Health Service.

Language : English

11.

Comparative Efficacy and Tolerability of Antipsychotics for Juvenile Psychotic Disorders: A Systematic Review and Network Meta-Analysis.

Author: YeeCaitlin S, BahjiAnees, LolichMaria, VázquezGustavo H, BaldessariniRoss J

Treat psychotic disorders

This study aimed to compare the short- and long-term efficacy and safety of antipsychotics for treating psychotic disorders in children and adolescents.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.
Systematic ReviewA review that systematically collects, evaluates, and integrates relevant research to answer a specific research question.

Language : English

13.

Clinically Significant Drug-Drug Interactions with Agents for Attention-Deficit/Hyperactivity Disorder.

Author: SchoretsanitisGeorgios, de LeonJose, EapChin B, KaneJohn M, PaulzenMichael

Drug interactions

This article provides an overview of pharmacokinetic drug-drug interactions (DDIs) for agents prescribed for attention-deficit/hyperactivity disorder (ADHD).

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

14.

Beyond stimulants: a systematic review of randomised controlled trials assessing novel compounds for ADHD.

Author: NageyeFatuma, CorteseSamuele

ADHD treatment

This systematic review explores recent randomized controlled trials on novel non-stimulant medications for attention-deficit/hyperactivity disorder (ADHD), including Dasotraline, Viloxazine, Centanafadine SR, OPC-64005, Fasoracetam, Metadoxine, Vortioxetine, Tipepidine Hibenzate, Oxytocin, Sativex, Mazindol, and Molindone hydrochloride. While these agents may not surpass stimulants in efficacy, they might offer comparable or better tolerability and contribute to a more personalized approach to ADHD treatment.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
Research Support, U.S. Gov't, Non-P.H.S.Research funding provided by US government agencies other than the Public Health Service.
Systematic ReviewA review that systematically collects, evaluates, and integrates relevant research to answer a specific research question.

Language : English

15.

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

Author: RobbAdelaide S, SchwabeStefan, Ceresoli-BorroniGianpiera, NasserAzmi, YuChungping, MarcusRonald, CandlerShawn A, FindlingRobert L

Impulsive aggression treatment
Maladaptive aggression treatment

Impulsive aggression (IA) is a common feature of various neuropsychiatric disorders and can be challenging to treat. The author proposes the establishment of a new drug class, anti-maladaptive aggression agents, to better address IA. The review explores the current challenges in treating IA and examines the potential of SPN-810, an extended-release molindone, as a novel IA pharmacotherapy.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

17.

Reproductive toxicology studies supporting the safety of molindone, a dopamine receptor antagonist.

Author: GopalakrishnanGopakumar, GanigerShivaputhrappa, WhiteTacey E K, YuChungping

Treats impulsive aggression

Molindone, a drug for ADHD, is being studied for impulsive aggression. Studies in animals have shown that molindone is safe for reproduction, but more research is needed.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

18.

Predictors and Moderators of Antipsychotic-Related Weight Gain in the Treatment of Early-Onset Schizophrenia Spectrum Disorders Study.

Author: TaylorJerome H, JakubovskiEwgeni, GabrielDaniel, BlochMichael H

Antipsychotic weight gain

Antipsychotic choice is extremely important for predicting future weight gain. We found that younger age did not predict greater weight gain.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
Research Support, U.S. Gov't, P.H.S.Research funding provided by the Public Health Service (PHS).

Language : English

19.

Efficacy, acceptability, and tolerability of antipsychotics in children and adolescents with schizophrenia: A network meta-analysis.

Author: KrauseMarc, ZhuYikang, HuhnMaximilian, Schneider-ThomaJohannes, BighelliIrene, ChaimaniAnna, LeuchtStefan

Improved schizophrenia symptoms
Prolactin increase
Sedation
Weight gain

This network-meta-analysis of 28 randomized controlled trials (RCTs) involving 3003 participants with schizophrenia found that clozapine was significantly more effective than other antipsychotics, while ziprasidone showed no efficacy. Most antipsychotics were more effective than placebo, but there were evidence gaps for some drugs and outcomes, particularly safety outcomes.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

20.

Antipsychotic drugs for the acute treatment of patients with a first episode of schizophrenia: a systematic review with pairwise and network meta-analyses.

Author: ZhuYikang, KrauseMarc, HuhnMaximilian, RothePhilipp, Schneider-ThomaJohannes, ChaimaniAnna, LiChunbo, DavisJohn M, LeuchtStefan

Negative symptom reduction
Symptom reduction
Akathisia
Parkinsonian symptoms
Prolactin release
Weight gain

Haloperidol seems to be a suboptimal treatment option for acute treatment of first-episode schizophrenia, but we found little difference between second-generation antipsychotics. The evidence was generally of low quality and the numbers of patients for each drug were small.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
Systematic ReviewA review that systematically collects, evaluates, and integrates relevant research to answer a specific research question.

Language : English

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