Comparative Pharmacology of Risperidone and Paliperidone.

Article Details

Citation

Corena-McLeod M

Comparative Pharmacology of Risperidone and Paliperidone.

Drugs R D. 2015 Jun;15(2):163-74. doi: 10.1007/s40268-015-0092-x.

PubMed ID
25943458 [ View in PubMed
]
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.

DrugBank Data that Cites this Article

Drugs
Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
Risperidone5-hydroxytryptamine receptor 2AProteinHumans
Yes
Antagonist
Details
Risperidone5-hydroxytryptamine receptor 2CProteinHumans
Unknown
Antagonist
Details
Risperidone5-hydroxytryptamine receptor 7ProteinHumans
Unknown
Antagonist
Details
RisperidoneAlpha-1A adrenergic receptorProteinHumans
Unknown
Antagonist
Details
RisperidoneAlpha-1B adrenergic receptorProteinHumans
Unknown
Antagonist
Details
RisperidoneAlpha-2B adrenergic receptorProteinHumans
Unknown
Antagonist
Details
RisperidoneAlpha-2C adrenergic receptorProteinHumans
Unknown
Antagonist
Details
RisperidoneD(2L) dopamine receptorProteinHumans
Unknown
Antagonist
Details
RisperidoneDopamine D2 receptorProteinHumans
Yes
Antagonist
Details
RisperidoneHistamine H1 receptorProteinHumans
Unknown
Antagonist
Details
Drug Interactions
DrugsInteraction
Paliperidone
Levothyroxine
The serum concentration of Paliperidone can be decreased when it is combined with Levothyroxine.
Paliperidone
Mifepristone
The serum concentration of Paliperidone can be decreased when it is combined with Mifepristone.
Paliperidone
Rifampicin
The serum concentration of Paliperidone can be decreased when it is combined with Rifampicin.
Paliperidone
Lorlatinib
The serum concentration of Paliperidone can be decreased when it is combined with Lorlatinib.
Paliperidone
Lumacaftor
The serum concentration of Paliperidone can be decreased when it is combined with Lumacaftor.