Side Effects of mesoridazine: A Synthesis of Findings from 18 Studies

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Original Abstract of the Article

Key Findings

Mesoridazine is a typical antipsychotic drug used to treat mental illnesses such as schizophrenia. Mesoridazine is produced as a metabolite of thioridazine. Mesoridazine shows higher affinity for dopamine receptors, α-adrenergic receptors, and muscarinic receptors than its parent drug, thioridazine.

Unlike clinically effective atypical antipsychotics, mesoridazine did not show inverse agonist activity at human 5-HT2C-INI receptors. 6 Like other typical antipsychotics, mesoridazine also showed inverse agonist activity at human D2, D3, and D4 receptors. 4 Mesoridazine has the potential to inhibit gap junction-mediated intercellular communication, which can affect the transmission of heartbeats. 2

Reasons for Side Effects

The side effects of mesoridazine may be due to its actions on dopamine receptors, α-adrenergic receptors, and muscarinic receptors. Mesoridazine binds to these receptors and inhibits their activity. Inhibition of dopamine receptors can cause extrapyramidal symptoms (EPS). Inhibition of α-adrenergic receptors can lead to hypotension and dizziness. Inhibition of muscarinic receptors can cause anticholinergic effects, such as dry mouth, constipation, blurred vision, and difficulty urinating.

Mesoridazine may also inhibit gap junction-mediated intercellular communication. 2 Gap junctions allow electrical signals to pass between heart cells, so inhibition by mesoridazine could cause cardiac conduction abnormalities. 2 Inhibition of gap junctions may contribute to the cardiotoxicity of mesoridazine. 2

Common Side Effects

Extrapyramidal Symptoms (EPS)

Mesoridazine, like other typical antipsychotics, can cause EPS. 6 EPS are involuntary muscle movements caused by dopamine receptor inhibition. 6 Symptoms of EPS include tremors, rigidity, akinesia, and dystonia. 6

Hypotension

Mesoridazine can cause hypotension. 11 Hypotension is a decrease in blood pressure caused by inhibition of α-adrenergic receptors. 11 Symptoms of hypotension include dizziness, lightheadedness, and fainting. 11

Anticholinergic Effects

Mesoridazine can cause anticholinergic effects. 11 Anticholinergic effects are caused by inhibition of muscarinic receptors. 11 Symptoms of anticholinergic effects include dry mouth, constipation, blurred vision, and difficulty urinating. 11

Cardiotoxicity

Mesoridazine can cause cardiotoxicity. 2 Cardiotoxicity may be caused by inhibition of gap junction-mediated intercellular communication. 2 Symptoms of cardiotoxicity include arrhythmias, atrial fibrillation, and cardiac arrest. 2

Weight Gain

Mesoridazine can cause weight gain. 13 Weight gain may be caused by antagonism or downregulation of serotonin receptors. 13

Countermeasures for Side Effects

Extrapyramidal Symptoms (EPS)

Anticholinergic drugs can be used to prevent EPS. 6 Antiparkinsonian drugs can be used to treat EPS. 6

Hypotension

Reducing the dosage of mesoridazine can help prevent hypotension. 11 Hydration can be effective in treating hypotension. 11 It is also important to be cautious when standing up. 11

Anticholinergic Effects

Reducing the dosage of mesoridazine can help prevent anticholinergic effects. 11

Cardiotoxicity

Reducing the dosage of mesoridazine can help prevent cardiotoxicity. 2 It is also important to monitor heart function regularly. 2

Weight Gain

Diet and exercise can help prevent weight gain. 13 Reducing the dosage of mesoridazine can also be effective. 13

Comparison Between Studies

Common Points

These studies indicate that mesoridazine can cause several side effects. These side effects include EPS, hypotension, anticholinergic effects, cardiotoxicity, and weight gain. 6 11 2 13

Differences

These studies explore different aspects of mesoridazine's side effects, including mechanisms and severity. 6 11 2 13 For example, 6 investigates the inverse agonist activity of mesoridazine. On the other hand, 11 investigates the pharmacokinetics and side effects of mesoridazine. These studies provide important information for understanding the overall picture of mesoridazine's side effects.

Points to Note for Application in Real Life

Mesoridazine is a medication that can be effective in treating mental illnesses such as schizophrenia, but it is important to consider the potential for side effects. 6 It is important to consult with a doctor to understand the risks and benefits of mesoridazine before taking it. 6

Limitations of Current Research

Research on the side effects of mesoridazine is not yet sufficient. Further research is needed to gain a deeper understanding of the mechanisms and severity of mesoridazine's side effects. 6 11 2 13

Directions for Future Research

To gain a deeper understanding of the mechanisms of mesoridazine's side effects, the following research is needed. 6 11 2 13

  • Research to investigate how mesoridazine interacts with various receptors in detail.
  • Research to elucidate the mechanisms of occurrence of side effects caused by mesoridazine.
  • Research to develop new treatments to reduce the side effects of mesoridazine.

Conclusion

Mesoridazine is a medication that can be effective in treating mental illnesses such as schizophrenia, but there is a risk of side effects. 6 It is important to consult with a doctor to understand the risks and benefits of mesoridazine before taking it. 6 Research on the side effects of mesoridazine is not yet sufficient. Further research is needed to better understand side effects. 6 11 2 13

Literature analysis of 18 papers
Positive Content
11
Neutral Content
3
Negative Content
4
Article Type
1
0
0
4
18
1.

Hospitalization risk associated with typical and atypical antipsychotic use in community-dwelling elderly patients.

Author: AparasuRajender R, JanoElda, JohnsonMichael L, ChenHua

Antipsychotic adverse effects

Antipsychotic medications can have adverse effects in elderly patients, who are more susceptible due to age-related changes in drug metabolism and response. This abstract highlights the need for more research on the impact of antipsychotics on hospitalizations in the elderly.

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.

Effect of thioridazine on gap junction intercellular communication in connexin 43-expressing cells.

Author: MatesicD F, AbifadelD N, GarciaE L, JannM W

Cardiac conduction side effects

This study tested the effect of thioridazine and mesoridazine on gap junction-mediated intercellular communication between cells. The drugs inhibited gap junction-mediated intercellular communication, which may contribute to the cardiac side-effects observed in patients taking these medications.

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.

Language : English

3.

Characterization of human cytochrome p450 enzymes involved in the metabolism of the piperidine-type phenothiazine neuroleptic thioridazine.

Author: WójcikowskiJacek, MaurelPatrick, DanielWładysława A

Neuroleptic metabolism understanding
Cardiotoxicity
Drug interactions

CYP1A2 and CYP3A4 are the main enzymes responsible for 5-sulfoxidation and N-demethylation of thioridazine, while CYP2D6 is the basic enzyme that catalyzes mono-2- and di-2-sulfoxidation.

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

4.

Intrinsic efficacy of antipsychotics at human D2, D3, and D4 dopamine receptors: identification of the clozapine metabolite N-desmethylclozapine as a D2/D3 partial agonist.

Author: BursteinE S, MaJ, WongS, GaoY, PhamE, KnappA E, NashN R, OlssonR, DavisR E, HacksellU, WeinerD M, BrannM R

Antipsychotic effect
Low EPS
Extrapyramidal symptoms

This study examines the molecular basis of extrapyramidal symptoms (EPS) associated with antipsychotic drugs. It finds that atypical antipsychotics like clozapine and aripiprazole have partial agonist properties at D2 and D3 receptors, which may contribute to their lower EPS incidence.

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

5.

Physical health monitoring of patients with schizophrenia.

Author: MarderStephen R, EssockSusan M, MillerAlexander L, BuchananRobert W, CaseyDaniel E, DavisJohn M, KaneJohn M, LiebermanJeffrey A, SchoolerNina R, CovellNancy, StroupScott, WeissmanEllen M, WirshingDonna A, HallCatherine S, PogachLeonard, Pi-SunyerXavier, BiggerJ Thomas, FriedmanAlan, KleinbergDavid, YevichSteven J, DavisBonnie, ShonSteven

Improved physical health monitoring

This article discusses recommendations for improving physical health monitoring of patients with schizophrenia in outpatient settings. It highlights the importance of addressing chronic physical illnesses and improving life expectancy for individuals with schizophrenia.

Consensus Development ConferenceA conference organized by the National Institutes of Health (NIH) to develop consensus and recommendations on medical issues.
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.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

6.

Inverse agonist actions of typical and atypical antipsychotic drugs at the human 5-hydroxytryptamine(2C) receptor.

Author: RauserL, SavageJ E, MeltzerH Y, RothB L

This study examined the relationship among 5-HT2C inverse agonist potency, efficacy, and atypical antipsychotic drug status in HEK-293 cells of a large number of typical and atypical antipsychotic drugs.

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

8.

The influence of selective serotonin reuptake inhibitors (SSRIs) on the pharmacokinetics of thioridazine and its metabolites: in vivo and in vitro studies.

Author: DanielW A, SyrekM, HaduchA, WójcikowskiJ

Dangerous combination
Serious side effects

Fluoxetine significantly increased the plasma concentrations of thioridazine and its metabolites, while sertraline tended to decrease thioridazine concentrations. Coadministration of thioridazine and sertraline seems to be safe.

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

9.

Clonidine does not potentiate the antipsychotic effects of neuroleptics in chronically ill patients.

Author: HedgesS, El-MallakhR S, IssaF, ElkashefA, BigelowL B, WyattR J

Antipsychotic treatment
Side effects

Combining clonidine with neuroleptics did not provide greater effectiveness than neuroleptics alone in treating chronic psychotic patients.

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.
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.

Language : English

10.

A fixed dose study of the plasma concentration and clinical effects of thioridazine and its major metabolites.

Author: CohenB M, LipinskiJ F, WaternauxC

Improves clinical outcome
Treats psychosis
Blurred vision
Dry mouth

Thioridazine, a drug for psychosis, was given to 53 patients for 2 weeks. Drug levels varied widely between patients, but the relative levels of thioridazine to mesoridazine and thioridazine to sulforidazine were consistent. Although patients showed improvement even with the lowest dose, the highest plasma levels of drug did not show the best clinical outcome. This suggests that the current doses of neuroleptics may be excessive.

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, P.H.S.Research funding provided by the Public Health Service (PHS).

Language : English

11.

Metabolism of thioridazine in the elderly.

Author: CohenB M, SommerB R

Effective for elderly
Increased serum concentrations
Increased side effects

Elderly patients showed higher serum concentrations of thioridazine and its metabolites, and experienced more frequent and severe side effects compared to younger adults after a single dose of thioridazine.

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, P.H.S.Research funding provided by the Public Health Service (PHS).

Language : English

12.

Dopamine neurochemical profile of atypical antipsychotics resembles that of D-1 antagonists.

Author: AltarC A, BoyarW C, WasleyA, GerhardtS C, LiebmanJ M, WoodP L

Minimal dopamine release
Increased dopamine metabolism

Atypical antipsychotics, unlike typical antipsychotics, were found to increase dopamine metabolism but not release in mice. This suggests that their mechanism of action may be related to D-1 receptor antagonism.

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

13.

Psychotropic drug induced weight gain: mechanisms and management.

Author: BernsteinJ G

Fluoxetine and fenfluramine may promote weight loss
Appetite stimulation with many psychotropic medications
Weight gain with many psychotropic medications

Many psychotropic medications have appetite stimulation and weight gain as side effects. Serotonin antagonists or downregulators are more likely to produce weight gain, while drugs with a pronounced serotonergic action are more likely to promote weight loss.

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.

Mesoridazine -- a pharmacodynamic and pharmacokinetic profile.

Author: GershonS, SakalisG, BowersP A

Effective for other psychiatric disorders
Effective for schizophrenia

Mesoridazine was effective in treating schizophrenia and other psychiatric disorders. Its effectiveness in patients refractory to other neuroleptics may be related to its slow rate of inactivation.

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

15.

Interactions of neuroleptic metabolites with dopaminergic, alpha adrenergic and muscarinic cholinergic receptors.

Author: BylundD B

Autonomic side effects
Extrapyramidal side effects

Metabolite potency at dopaminergic, alpha adrenergic, and muscarinic cholinergic receptors correlated with clinical data on drug potency and side effects. The findings suggest that metabolites contribute significantly to both therapeutic and side effects of neuroleptics.

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

16.

Dysphoric response to neuroleptics as a predictor of treatment outcome with schizophrenics. A comparative study of haloperidol versus mesoridazine.

Author: WhiteK, BuskJ, EatonE, GomezG, RazaniJ, SloaneR B

Antipsychotic effect
Side effects

Haloperidol and mesoridazine were equally effective in treating schizophrenia, with side effects occurring as expected. An index of dysphoric response did not predict outcome in this short trial.

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.

Language : English

17.

Polygraphic sleep studies in rats and humans: their use in psychopharmacological research.

Author: LoewD M, SpiegelR

Polygraphic sleep studies were found to be a sensitive and stable method for studying the effects of centrally acting drugs.

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.
Controlled Clinical TrialA clinical trial that evaluates the effectiveness of a treatment by comparing a group that receives the intervention with a group that receives a placebo or standard treatment.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

18.

Psychotropic drug induced weight gain: mechanisms and management.

Author: BernsteinJ G

Fluoxetine and fenfluramine may promote weight loss
Appetite stimulation with many psychotropic medications
Weight gain with many psychotropic medications

Many psychotropic medications have appetite stimulation and weight gain as side effects. Serotonin antagonists or downregulators are more likely to produce weight gain, while drugs with a pronounced serotonergic action are more likely to promote weight loss.

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

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