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Antidepressant efficacy of cariprazine in bipolar disorder and the role of its pharmacodynamic properties: A hypothesis based on data

The treatment of bipolar depression is one of the most challenging needs in contemporary psychiatry. Currently, only quetiapine, olanzapine-fluoxetine combination, lurasidone, cariprazine, and recently lumateperone have been FDA-approved to treat this condition. The neurobiology of bipolar depression and the possible targets of bipolar antidepressant therapy remain elusive. The current study investigated whether the pharmacodynamic properties of cariprazine fit into a previously developed model which was the first to be derived based on the strict combination of clinical and preclinical data. The authors performed a systematic review of the literature to identify the pharmacodynamic properties of cariprazine. The original model suggests that a constellation of effects on different receptors is necessary and that serotonin reuptake inhibition does not appear to play a significant role in acute bipolar depression. On the contrary, norepinephrine activity seems to be necessary. Probably the early antidepressant effect can be achieved through an agonistic activity at 5HT-1A and antagonism at alpha1 noradrenergic and 5-HT2A receptors, but the presence of a norepinephrine reuptake inhibition appears essential to sustain it. Overall, the properties of cariprazine fit well the proposed model and add to its validity. A point that needs further clarification is norepinephrine reuptake inhibition which is not yet fully studied for cariprazine.

 

Comments：

The study investigated whether the pharmacodynamic properties of cariprazine fit into a previously developed model for the treatment of bipolar depression, which was derived based on a combination of clinical and preclinical data. The study authors performed a systematic review of the literature to identify the pharmacodynamic properties of cariprazine and found that its properties fit well with the proposed model.

The original model suggests that a combination of effects on different receptors is necessary for the treatment of bipolar depression, and that serotonin reuptake inhibition does not appear to play a significant role in acute bipolar depression. Instead, norepinephrine activity seems to be necessary. The early antidepressant effect may be achieved through an agonistic activity at 5HT-1A and antagonism at alpha1 noradrenergic and 5-HT2A receptors, but the presence of norepinephrine reuptake inhibition appears essential to sustain it.

While the properties of cariprazine fit well with the proposed model, the authors note that further clarification is needed regarding its norepinephrine reuptake inhibition. Overall, this study provides insight into the potential pharmacological targets for bipolar antidepressant therapy and highlights the need for further research in this area.

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Cat.No. Product Name Information
S5714 lurasidone Lurasidone (SM-13496) is a second-generation antipsychotic agent that exhibits full antagonism at dopamine D2 and serotonin 5-HT2A receptors with binding affinities Ki = 1 nM and Ki = 0.5 nM, respectively. It also has high affinity for serotonin 5-HT7 receptors (Ki = 0.5 nM), partial agonist activity at 5-HT1A receptors (Ki = 6.4 nM) and lacks affinity for histamine H1 and muscarinic M1 receptors.

Related Targets

5-HT Receptor Dopamine Receptor