Managing ADHD and disruptive behaviour disorders with combination psychostimulant and antipsychotic treatment

Elbe, Dean; Barr, Alasdair M.; Honer, William G.; Procyshyn, Ric M.

doi:10.1503/jpn.130288

Cited by 3 publications

(11 citation statements)

References 10 publications

(9 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, in the [ 35 S]GTPγS binding assay, SPN-810M at concentrations ranging from 1 nM to 10 µM showed a similar IC 50 of 0.0844 µM in response to control agonist for D 2S ( Figure 2A ). Similarly, SPN-810M (1 nM–10 µM) was found to act as an antagonist for the D 2L receptor with an IC 50 of 0.11 µM in the [ 35 S]GTPγS binding assay ( Figure 2B ). At the SPN-810M concentrations tested (3 nM–10 µM), the inhibitory effect on D 1 , D 3 , and D 5 receptors was not as potent as that noted for D 2S and D 2L , with IC 50 values ranging from 3.2 µM to 8.3 µM.…”

Section: Resultsmentioning

confidence: 84%

“…The concentration of SPN-810M at which percent inhibition of control agonist response is reduced by half (IC 50 ) was identified as 0.14 µM. Furthermore, in the [ 35 S]GTPγS binding assay, SPN-810M at concentrations ranging from 1 nM to 10 µM showed a similar IC 50 of 0.0844 µM in response to control agonist for D 2S ( Figure 2A ). Similarly, SPN-810M (1 nM–10 µM) was found to act as an antagonist for the D 2L receptor with an IC 50 of 0.11 µM in the [ 35 S]GTPγS binding assay ( Figure 2B ).…”

Section: Resultsmentioning

confidence: 88%

“…A GTPγS binding assay was used to evaluate the antagonist activity of SPN-810M at the human D 2S and D 2L receptors expressed in transfected CHO cells. Total [ 35 S]GTPγS (guanine 5′-O-[γ-thio]triphosphate) binding was performed in duplicate based on the method used by Senogles et al, with minor modifications. 20 Briefly, test compounds were preincubated with the membranes (D 2S : 0.05 mg/mL; D 2L : 0.1 mg/mL) and GDP (guanosine 5′-diphosphate) (D 2S : 3 µM; D 2L : 10 µM) in modified HEPES buffer (20 mM HEPES, pH 7.4; 100 mM NaCl; 10 mM MgC1 2 ; 1 mM EDTA; 1 mM DTT) for 20 minutes and scintillation proximity assay beads were then added for another 60 minutes at 30°C.…”

Section: Methodsmentioning

confidence: 99%

“…20 Briefly, test compounds were preincubated with the membranes (D 2S : 0.05 mg/mL; D 2L : 0.1 mg/mL) and GDP (guanosine 5′-diphosphate) (D 2S : 3 µM; D 2L : 10 µM) in modified HEPES buffer (20 mM HEPES, pH 7.4; 100 mM NaCl; 10 mM MgC1 2 ; 1 mM EDTA; 1 mM DTT) for 20 minutes and scintillation proximity assay beads were then added for another 60 minutes at 30°C. The reaction was initiated by 0.3 nM [ 35 S]GTPγS for an additional 30 minutes at 30°C for D 2S and 15 minutes at 30°C for D 2L incubation period. The bound [ 35 S]GTPγS was detected using a scintillation counter (PerkinElmer Microbeta).…”

Section: Methodsmentioning

confidence: 99%

“…The reaction was initiated by 0.3 nM [ 35 S]GTPγS for an additional 30 minutes at 30°C for D 2S and 15 minutes at 30°C for D 2L incubation period. The bound [ 35 S]GTPγS was detected using a scintillation counter (PerkinElmer Microbeta).…”

Section: Methodsmentioning

confidence: 99%

See 4 more Smart Citations

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

Yu¹,

Gopalakrishnan²

2018

JEP

View full text Add to dashboard Cite

BackgroundImpulsive aggression (IA) is considered a maladaptive form of aggression that is reactive and overt and occurs outside of the acceptable social context. Many children and adolescents with attention-deficit/hyperactivity disorder (ADHD) display clinically significant aggression, with the predominant subtype being IA. However, there is currently no Food and Drug Administration-approved medication specifically to treat IA. The pathophysiology of IA is not fully understood, although it has been suggested to include the dopamine, norepinephrine, and serotonin systems.MethodsSPN-810 (extended-release molindone) is being developed for the novel indication of IA and is currently being studied in patients treated for ADHD. Molindone is an indole derivative and a dopamine D2 receptor antagonist.ResultsThe in vitro pharmacological studies described in the current manuscript demonstrate that the active substance molindone (SPN-810M) is a potent antagonist for the dopamine receptors, D2S and D2L, and the serotonin receptor, 5-HT2B, at therapeutic concentrations. The in vitro studies further demonstrate that the antagonist effect of SPN-810M is due to the parent drug and not the metabolites, and that the antagonism is not affected by the presence of norepinephrine or dopamine neurotransmitters. In addition, studies investigating the potential differential effects of the enantiomers of SPN-810M have demonstrated that the R(−) enantiomer is more potent than S(+), showing greater regulatory effect on D2S and D2L receptors.ConclusionOverall, the results of the in vitro SPN-810M pharmacological studies provide some insight into how SPN-810M modulates the serotonin and dopamine pathways that play a role in IA.

show abstract

Section: Resultsmentioning

confidence: 84%

Section: Resultsmentioning

confidence: 88%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

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

Yu¹,

Gopalakrishnan²

2018

JEP

View full text Add to dashboard Cite

show abstract

Low-dose quetiapine complements stimulant response in attention deficit hyperactivity disorder and more

Naguy

2016

Therapeutic Advances in Psychopharmacology

View full text Add to dashboard Cite

Long-acting injectable antipsychotics for early psychosis: A comprehensive systematic review

et al. 2022

View full text Add to dashboard Cite

Aim Long acting injectable (LAI) antipsychotics are an alternative to oral antipsychotic (OAP) treatment and may be beneficial for patients in the early stages of schizophrenia. This study aims to provide a comprehensive review on the efficacy of first-generation and second-generation LAI antipsychotics in recent-onset, first-episode, and early psychosis patients. Methods MEDLINE, EMBASE, PsycINFO, and Web of Science Core databases were used to search for studies that used LAIs in early psychosis patients. Studies published up to 06 Jun 2019 were included with no language restrictions applied. Inclusion criteria were a diagnosis of schizophrenia or related disorder, where patients were in their first episode or had a duration of illness ≤5 years. Results 33 studies were included: 8 RCTs, 4 post-hoc analyses, 2 case reports, and 19 naturalistic studies. The majority of studies evaluated risperidone LAIs (N = 14) and paliperidone palmitate (N = 10), while the remainder investigated fluphenazine decanoate (N = 3), flupentixol decanoate (N = 2), and aripiprazole (N = 1). Two studies did not specify the LAI formulation used, and one cohort study compared the efficacy of multiple different LAI formulations. Conclusions While the majority of data is based on naturalistic studies investigating risperidone LAIs or paliperidone palmitate, LAIs may be an effective treatment for early psychosis patients in terms of adherence, relapse reduction, and symptom improvements. There is still a need to conduct more high quality RCTs that investigate the efficacy of different LAI formulations in early psychosis patients.

show abstract

Managing ADHD and disruptive behaviour disorders with combination psychostimulant and antipsychotic treatment

Cited by 3 publications

References 10 publications

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

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

Low-dose quetiapine complements stimulant response in attention deficit hyperactivity disorder and more

Long-acting injectable antipsychotics for early psychosis: A comprehensive systematic review

Contact Info

Product

Resources

About