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Comparative Pharmacology of Risperidone and Paliperidone.

Corena-McLeod M - Drugs R D (2015)

Bottom Line: Differences in receptor binding, 5-HT2A/D2 (serotonin/dopamine) binding ratios, and mitochondrial proteomics suggest that the effects of risperidone and paliperidone on neuronal firing, regulation of mitochondrial function, and movement are different.Thus, the risperidone 5-HT2A/D2 binding ratio is significantly lower than the paliperidone 5-HT2A/D2 binding ratio.It is apparent that the presence of a hydroxyl group in the paliperidone molecule confers increased hydrophilicity to this drug compared with its parent, risperidone; thus, this contributes to differential effects on mitochondrial movement, protein expression, and phosphorylation.

View Article: PubMed Central - PubMed

Affiliation: Biochemical consultant, 3682 Summerlin Lane, Jacksonville, FL, 32224, USA, pilarcorena@gmail.com.

ABSTRACT
Antipsychotics, risperidone, and risperidone's active metabolite, paliperidone (9-hydroxyrisperidone), are related molecules used for the treatment of schizophrenia and related disorders. Differences in receptor binding, 5-HT2A/D2 (serotonin/dopamine) binding ratios, and mitochondrial proteomics suggest that the effects of risperidone and paliperidone on neuronal firing, regulation of mitochondrial function, and movement are different. This review seeks to explore the most significant differences at the molecular level between risperidone and paliperidone, as reported in preclinical studies. Although risperidone shows higher affinity for 5-HT receptors, paliperidone does not fit this profile. Thus, the risperidone 5-HT2A/D2 binding ratio is significantly lower than the paliperidone 5-HT2A/D2 binding ratio. Paliperidone, similar to lithium and valproate, affects expression levels and phosphorylation of complex I and V proteins in synaptoneurosomal preparations of rat prefrontal cortex, suggesting that paliperidone behaves as a mood stabilizer. It is apparent that the presence of a hydroxyl group in the paliperidone molecule confers increased hydrophilicity to this drug compared with its parent, risperidone; thus, this contributes to differential effects on mitochondrial movement, protein expression, and phosphorylation. These differences are reflected in synaptic plasticity and neuronal firing and have only recently been implicated in the mechanisms of mitochondrial function and movement.

No MeSH data available.


Related in: MedlinePlus

As described in 2013 by Corena-McLeod and collaborators, paliperidone-induced phosphorylation of actin, tubulin, and other filaments promoting mitochondrial anterograde transport. a Serotonin (blue spheres) promotes this anterograde movement. b Dopamine (red spheres) has been shown to inhibit mitochondrial anterograde transport
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Fig4: As described in 2013 by Corena-McLeod and collaborators, paliperidone-induced phosphorylation of actin, tubulin, and other filaments promoting mitochondrial anterograde transport. a Serotonin (blue spheres) promotes this anterograde movement. b Dopamine (red spheres) has been shown to inhibit mitochondrial anterograde transport

Mentions: Neuronal firing may occur through energy release from glucose (ATP generation through complex V) as a result of mitochondrial function through the ETC. Therefore, changes in mitochondrial function and movement to the synapse will have profound effects on ATP production and subsequently on neuronal firing. The direction and extent of mitochondrial anterograde movement, as well as mitochondrial function, are likely regulated by interactions between risperidone and paliperidone with 5-HT2A and D2 receptors. As the affinity ratios revealed, these interactions are different for each of these drugs, suggesting that they have differential effects on synaptoneurosomal energetics (Fig. 4).Fig. 4


Comparative Pharmacology of Risperidone and Paliperidone.

Corena-McLeod M - Drugs R D (2015)

As described in 2013 by Corena-McLeod and collaborators, paliperidone-induced phosphorylation of actin, tubulin, and other filaments promoting mitochondrial anterograde transport. a Serotonin (blue spheres) promotes this anterograde movement. b Dopamine (red spheres) has been shown to inhibit mitochondrial anterograde transport
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4488186&req=5

Fig4: As described in 2013 by Corena-McLeod and collaborators, paliperidone-induced phosphorylation of actin, tubulin, and other filaments promoting mitochondrial anterograde transport. a Serotonin (blue spheres) promotes this anterograde movement. b Dopamine (red spheres) has been shown to inhibit mitochondrial anterograde transport
Mentions: Neuronal firing may occur through energy release from glucose (ATP generation through complex V) as a result of mitochondrial function through the ETC. Therefore, changes in mitochondrial function and movement to the synapse will have profound effects on ATP production and subsequently on neuronal firing. The direction and extent of mitochondrial anterograde movement, as well as mitochondrial function, are likely regulated by interactions between risperidone and paliperidone with 5-HT2A and D2 receptors. As the affinity ratios revealed, these interactions are different for each of these drugs, suggesting that they have differential effects on synaptoneurosomal energetics (Fig. 4).Fig. 4

Bottom Line: Differences in receptor binding, 5-HT2A/D2 (serotonin/dopamine) binding ratios, and mitochondrial proteomics suggest that the effects of risperidone and paliperidone on neuronal firing, regulation of mitochondrial function, and movement are different.Thus, the risperidone 5-HT2A/D2 binding ratio is significantly lower than the paliperidone 5-HT2A/D2 binding ratio.It is apparent that the presence of a hydroxyl group in the paliperidone molecule confers increased hydrophilicity to this drug compared with its parent, risperidone; thus, this contributes to differential effects on mitochondrial movement, protein expression, and phosphorylation.

View Article: PubMed Central - PubMed

Affiliation: Biochemical consultant, 3682 Summerlin Lane, Jacksonville, FL, 32224, USA, pilarcorena@gmail.com.

ABSTRACT
Antipsychotics, risperidone, and risperidone's active metabolite, paliperidone (9-hydroxyrisperidone), are related molecules used for the treatment of schizophrenia and related disorders. Differences in receptor binding, 5-HT2A/D2 (serotonin/dopamine) binding ratios, and mitochondrial proteomics suggest that the effects of risperidone and paliperidone on neuronal firing, regulation of mitochondrial function, and movement are different. This review seeks to explore the most significant differences at the molecular level between risperidone and paliperidone, as reported in preclinical studies. Although risperidone shows higher affinity for 5-HT receptors, paliperidone does not fit this profile. Thus, the risperidone 5-HT2A/D2 binding ratio is significantly lower than the paliperidone 5-HT2A/D2 binding ratio. Paliperidone, similar to lithium and valproate, affects expression levels and phosphorylation of complex I and V proteins in synaptoneurosomal preparations of rat prefrontal cortex, suggesting that paliperidone behaves as a mood stabilizer. It is apparent that the presence of a hydroxyl group in the paliperidone molecule confers increased hydrophilicity to this drug compared with its parent, risperidone; thus, this contributes to differential effects on mitochondrial movement, protein expression, and phosphorylation. These differences are reflected in synaptic plasticity and neuronal firing and have only recently been implicated in the mechanisms of mitochondrial function and movement.

No MeSH data available.


Related in: MedlinePlus