From the Guidelines
Paliperidone's mechanism of action is primarily based on its ability to block dopamine D2 receptors and serotonin 5-HT2A receptors in the brain, which is responsible for its therapeutic effects in treating schizophrenia and schizoaffective disorder. This dual receptor blockade contributes to its efficacy in managing symptoms of these conditions. As an atypical antipsychotic, paliperidone has a higher affinity for 5-HT2A receptors compared to typical antipsychotics, which results in fewer extrapyramidal side effects 1.
The medication's action on other receptors, such as alpha-1 and alpha-2 adrenergic receptors and H1 histamine receptors, explains some of its side effects, including orthostatic hypotension and sedation. Paliperidone is the active metabolite of risperidone but has a longer half-life, allowing for once-daily dosing. Its pharmacological profile is supported by studies on atypical antipsychotics, which suggest that these agents are at least as effective as traditional neuroleptics for positive symptoms and possibly more effective for negative symptoms 1.
Key points about paliperidone's mechanism of action include:
- Dual blockade of dopamine D2 and serotonin 5-HT2A receptors
- Higher affinity for 5-HT2A receptors, reducing extrapyramidal side effects
- Action on alpha-1, alpha-2 adrenergic, and H1 histamine receptors, contributing to side effects
- Longer half-life compared to risperidone, allowing for once-daily dosing
- Availability in immediate-release and extended-release formulations to improve medication adherence and minimize peak-related side effects.
From the FDA Drug Label
Paliperidone is the major active metabolite of risperidone. The mechanism of action of paliperidone in schizophrenia is unclear. However, the drug's therapeutic effect in schizophrenia could be mediated through a combination of central dopamine Type 2 (D 2) and serotonin Type 2 (5HT 2A) receptor antagonism.
The mechanism of action of paliperidone is not fully understood, but it is believed to involve antagonism of dopamine Type 2 (D2) and serotonin Type 2 (5HT2A) receptors. Paliperidone also acts as an antagonist at α1 and α2 adrenergic receptors and H1 histaminergic receptors. The drug has no affinity for cholinergic muscarinic or β1- and β2-adrenergic receptors 2.
- Key points:
- Mechanism of action not fully understood
- Believed to involve D2 and 5HT2A receptor antagonism
- Also acts as an antagonist at α1 and α2 adrenergic receptors and H1 histaminergic receptors
- No affinity for cholinergic muscarinic or β1- and β2-adrenergic receptors
From the Research
Mechanism of Action
- Paliperidone's mechanism of action is attributed to the antagonism of brain dopamine D2 and serotonin 5-HT2A receptors 3, 4, 5.
- The drug has a greater affinity for serotonin type 2A-receptor blockade relative to dopamine type 2-receptor blockade, similar to other atypical antipsychotics 4.
- This receptor-binding profile is similar to that of risperidone and ziprasidone, with paliperidone differing from risperidone in its relatively low extent of enzymatic metabolism 4.
Pharmacological Characteristics
- Paliperidone has a smooth fluctuation in plasma drug concentrations, predominantly renal excretion, low risk of causing hepatic impairment, and low drug-drug interaction 6.
- The advanced-generation osmotic release delivery system of paliperidone allows for the avoidance of dosage adjustment when initiating therapy and may decrease the frequency of antido-paminergic effects 4.
Clinical Implications
- Paliperidone has been shown to reduce symptoms of schizophrenia and schizoaffective disorder, with significant improvements in psychopathology, functioning, and relapse compared to placebo 3, 4, 6.
- The drug has a similar adverse-effect profile to risperidone, except for an increased rate of hyperprolactinemia 4.
- Paliperidone may have a lower prevalence of adverse events due to its extended-release formulation and slow release of the active ingredient 7.