Pathophysiological Roles of Serotonergic System in Regulating Extrapyramidal Motor Functions

Ohno, Yukihiro; Shimizu, Saki; Tokudome, Kentaro

doi:10.1248/bpb.b13-00310

Cited by 34 publications

(44 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus, it is now widely acknowledged, although awaiting further confirmation, that receptors other than dopaminergic (i.e. serotonergic, adrenergic, and cholinergic) might play an important role in the pathophysiology of NMS since they are known to take substantial part in extrapyramidal motor functions [90], thermoregulation, muscle metabolism [89], and mental status [16]. …”

Section: Discussionmentioning

confidence: 99%

“…In apparent contrast with this hypothesis, most SGAs antagonize 5-HT 2A receptors, and were even suggested for use in the treatment of serotonin syndrome. However, it is noteworthy that quetiapine, aripiprazole, clozapine, and ziprasidone share agonistic actions at 5-HT 1A receptors; their stimulation was thus proposed to contribute to lower degrees of hyperthermia or EPS that are observed in some cases of SGA-NMS [16, 90]. Moreover, it was recently hypothesized that long-term treatment with SGAs might determine unbalances in serotonergic neurotransmission, leading to sensitization towards SGAs and other psychotropic agents [94, 95].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Second-Generation Antipsychotics and Neuroleptic Malignant Syndrome: Systematic Review and Case Report Analysis

et al. 2015

View full text Add to dashboard Cite

BackgroundNeuroleptic malignant syndrome (NMS) is a rare, severe, idiosyncratic adverse reaction to antipsychotics. Second-generation antipsychotics (SGAs) were originally assumed to be free from the risk of causing NMS, however several cases of NMS induced by SGAs (SGA-NMS) have been reported.ObjectivesThe aim of this study was to systematically review available studies and case reports on SGA-NMS and compare the presentation of NMS induced by different SGAs.Data SourcesCitations were retrieved from PubMed up to November 2013, and from reference lists of relevant citations.Study Eligibility CriteriaEligibility criteria included (a) primary studies reporting data on NMS, with at least 50 % of the sample receiving SGAs; or (b) case reports and case reviews reporting on NMS induced by SGA monotherapy, excluding those due to antipsychotic withdrawal.Study Appraisal and Synthesis MethodsA standardized method for data extraction and coding was developed for the analysis of eligible case reports.ResultsSix primary studies and 186 individual cases of NMS induced by SGAs were included. Primary studies suggest that SGA-NMS is characterized by lower incidence, lower clinical severity, and less frequent lethal outcome than NMS induced by first-generation antipsychotics. Systematic analysis of case reports suggests that even the most recently marketed antipsychotics are not free from the risk of inducing NMS. Furthermore, clozapine-, aripiprazole- and amisulpride-induced NMS can present with atypical features more frequently than other SGA-NMS, i.e. displaying less intense extrapyramidal symptoms or high fever.LimitationsCase reports report non-systematic data, therefore analyses may be subject to bias.Conclusions and Implications of Key FindingsClinicians should be aware that NMS is virtually associated with all antipsychotics, including those most recently marketed. Although apparently less severe than NMS induced by older antipsychotics, SGA-NMS still represent a relevant clinical issue.Electronic supplementary materialThe online version of this article (doi:10.1007/s40268-014-0078-0) contains supplementary material, which is available to authorized users.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Second-Generation Antipsychotics and Neuroleptic Malignant Syndrome: Systematic Review and Case Report Analysis

et al. 2015

View full text Add to dashboard Cite

show abstract

“…To evaluate the potential beneficial effects of 5-HT 3 antagonists on antipsychotic-induced extrapyramidal side-effects, several drugs have also been tested against dopamine antagonist-induced catalepsy (Ohno et al, 2013). Ondansetron, bemesetron and granisetron were all found to reverse haloperidol-induced catalepsy in mice (Silva et al, 1995;Ohno et al, 2011).…”

Section: Dopamineantagonist-induced Behavioursmentioning

confidence: 99%

Can 5-HT3 antagonists contribute toward the treatment of schizophrenia?

Ellenbroek

Prinssen

2015

Behavioural Pharmacology

View full text Add to dashboard Cite

In one of his earlier papers, Lex Cools stated that the 'concept of an impaired balance between the in series connected […] dopamine system, […] 5-HT system and […] noradrenaline system offers a single coherent and integrated theory of schizophrenia' (Cools, 1975). Since then, considerable attention has focused on the interaction between dopamine and 5-HT and it is now well accepted that most antipsychotics (especially the second-generation drugs) modulate both dopaminergic and serotonergic receptors. However, the vast majority of research has focused on the 5-HT1A, 5-HT2A and 5-HT2C receptors. In the present paper, we review the literature pertaining to the 5-HT3 receptor, the only ionotropic 5-HT receptor. We discuss both the interactions between 5-HT3 receptors and dopamine, and the animal and human literature investigating the role of 5-HT3 receptors in schizophrenia. The results show that the interactions between 5-HT3 receptors and dopamine are complex, but that 5-HT3 receptors do not have a strong influence on the positive symptoms of schizophrenia. However, when added to standard antipsychotic medication, several recent studies have found that 5-HT3 receptor antagonists can induce a statistically significantly improvement in negative and cognitive symptoms. The implications of these findings in relation to animal modelling and drug development are discussed.

show abstract

“…Extrapyramidal motor functions are mainly regulated by the basal ganglia including the striatum (i.e., caudate-putamen) and the globus pallidus (GP), which forms the basal ganglia-thalamus-cerebral cortex neural circuit (Miguelez et al, 2014;Ohno et al, 2013;Shimizu and Ohno, 2013b;Somola, 2013) (Fig. 2).…”

Section: Pathophysiological Basismentioning

confidence: 99%

“…These drugs M a n u s c r i p t 10 2011a; Ohno et al, 2013;Shimizu and Ohno, 2013b). Therefore, a new vision emerges from this evidence that 5-HT receptors are a promising target in the treatment of PD.…”

Section: Introductionmentioning

confidence: 99%

New insight into the therapeutic role of the serotonergic system in Parkinson's disease

Ohno

Shimizu

Tokudome

et al. 2015

Progress in Neurobiology

Self Cite

View full text Add to dashboard Cite

Pathophysiological Roles of Serotonergic System in Regulating Extrapyramidal Motor Functions

Cited by 34 publications

References 26 publications

Second-Generation Antipsychotics and Neuroleptic Malignant Syndrome: Systematic Review and Case Report Analysis

Second-Generation Antipsychotics and Neuroleptic Malignant Syndrome: Systematic Review and Case Report Analysis

Can 5-HT3 antagonists contribute toward the treatment of schizophrenia?

New insight into the therapeutic role of the serotonergic system in Parkinson's disease

Contact Info

Product

Resources

About