Evaluation of the Effect of Cariprazine on Memory and Cognition in Experimental Rodent Models

Zlatanova, H.; Georgieva-Kotetarova, M.; Vilmosh, N.; Kandilarov, I.

doi:10.3390/ijerph192214748

Cited by 4 publications

(3 citation statements)

References 59 publications

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“…However, radioligand binding studies have shown no affinity of JJGW07 for 5-HT 6 receptors, suggesting that other biological targets are involved in its pharmacological effects. Importantly, the memory-enhancing activity is not only dependent on the modulation of 5-HT 6 receptors, as there are other antipsychotics, i.e., aripiprazole, brexpiprazole, or cariprazine, that show procognitive properties due to other mechanisms, including interactions with the 5-HT 1A and/or 5-HT 7 receptors [ 38 , 39 , 40 ].…”

Section: Discussionmentioning

confidence: 99%

Novel Multimodal Salicylamide Derivative with Antidepressant-like, Anxiolytic-like, Antipsychotic-like, and Anti-Amnesic Activity in Mice

et al. 2023

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Depression, anxiety, and schizophrenia may coexist in psychiatric patients. Moreover, these disorders are very often associated with cognitive impairments. However, pharmacotherapy of these conditions remains challenging due to limited drug effectiveness or numerous side effects. Therefore, there is an urgent need to develop novel multimodal compounds that can be used to treat depression, anxiety, and schizophrenia, as well as memory deficits. Thus, this study aimed to evaluate the potential antidepressant-like, anxiolytic-like, antipsychotic-like effects, and anti-amnesic properties, of the novel arylpiperazine derivative of salicylamide, JJGW07, with an affinity towards serotonin 5-HT1A, 5-HT2A, and 5-HT7 and dopamine D2 receptors. Firstly, we investigated the compound’s affinity for 5-HT6 receptors and its functional activity by using in vitro assays. JJGW07 did not bind to 5-HT6 receptors and showed antagonistic properties for 5-HT1A, 5-HT2A, 5-HT7, and D2 receptors. Based on the receptor profile, we performed behavioral studies in mice to evaluate the antidepressant-like, anxiolytic-like, and antipsychotic-like activity of the tested compound using forced swim and tail suspension tests; four-plate, marble-burying, and elevated plus maze tests; and MK-801- and amphetamine-induced hyperlocomotion tests, respectively. JJGW07 revealed antidepressant-like properties in the tail suspension test, anxiolytic-like effects in the four-plate and marble-burying tests, and antipsychotic-like activity in the MK-801-induced hyperlocomotion test. Importantly, the tested compound did not induce catalepsy and motor impairments or influence locomotor activity in rodents. Finally, to assess the potential procognitive and anti-amnesic properties of JJGW07, we used passive avoidance and object recognition tests in mice. JJGW07 demonstrated positive effects on long-term emotional memory and also ameliorated MK-801-induced emotional memory impairments in mice, but showed no procognitive properties in the case of recognition memory. Our results encourage the search for new compounds among salicylamide derivatives, which could be model structures with multitarget mechanisms of action that could be used in psychiatric disorder therapy.

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Section: Discussionmentioning

confidence: 99%

Novel Multimodal Salicylamide Derivative with Antidepressant-like, Anxiolytic-like, Antipsychotic-like, and Anti-Amnesic Activity in Mice

et al. 2023

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“…This beneficial effect on cognition is likely attributed to cariprazine's interaction with D3 receptors and agonism at 5-HT1A receptors. The cognitiveenhancing properties of cariprazine are probably the result of integrated modulation in the hippocampus, amygdala and prefrontal cortex [37].…”

Section: Pro-cognitive Effectmentioning

confidence: 99%

Cariprazine: An Antipsychotic Medication with High Therapeutic Potential

Wilanowska,

Greguła,

Stachyrak

et al. 2024

J Educ Health Sport

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Introduction and purposeCariprazine is an atypical antipsychotic drug approved for the treatment of schizophrenia, as well as manic and mixed episodes associated with bipolar disorder. It functions as a dopamine multifunctional agent, a partial agonist at dopamine and serotonin receptors. Unlike the majority of antipsychotics, which primarily target positive symptoms through dopaminergic antagonism, often neglecting negative, cognitive, and affective symptoms, the unique cariprazine's pharmacological profile, particularly potent blockade of D3 dopamine receptors, suggests the potential for numerous clinical applications. The aim of this study is to present current knowledge of cariprazine, focusing particularly on its mechanism of action, potential applications, adverse effects, and pharmacokinetic properties that could impact its clinical use.Methods and materialsA review of the literature available in the PubMed database was performed using the key words: cariprazine; atypical antipsychotic drug; antipsychotic medication; schizophrenia treatment; bipolar disorder treatment; mania treatment; depression treatment, dopamine agonist.ConclusionsCariprazine demonstrates a unique pharmacological profile, offering potential benefits in managing a wide range of psychiatric disorders, including schizophrenia, bipolar disorder (mania, depression, mixed episodes), unipolar depression, and co-occurring substance use disorders. Clinical studies have shown efficacy in reducing symptoms and improving negative and cognitive function, with a favorable metabolic profile, minimal impact on cardiovascular system, and generally mild adverse effect profile. However, further research is necessary to explore its full therapeutic potential and optimize its clinical use in diverse patient populations.

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“…Another study showed that D 3 R partial agonist activity of cariprazine, which produced functional antagonism, was involved in increased nucleus accumbens and hippocampal neurotransmitter effect possibly contributing to its antipsychotic effect (Huang et al , 2019). Lastly, another mouse study found that cariprazine’s beneficial effect on cognition (improved learning and memory in both short-term and long-term memory) was likely due to its affinity for D 3 R (Zlatanova et al , 2022).…”

Section: Introductionmentioning

confidence: 99%

Differentiating the third generation of antipsychotics: a focus on lumateperone’s similarities and differences

Munayco Maldonado,

Schwartz

2023

International Clinical Psychopharmacology

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The development of atypical antipsychotics has evolved to include newer pharmacodynamic properties. Lumateperone, aripiprazole, brexpiprazole, and cariprazine are all dopamine-2 receptor partial agonists with varying receptor affinities. This review aims to compare the clinical and pharmacodynamic differences among these four atypical antipsychotics, all of which are unique when compared to first- and second-generation antipsychotics. For consideration is further delineating these agents as being third-generation antipsychotics. PubMed searches were conducted to compile preclinical and clinical studies derived from animal models and human subjects. Information gathered included pharmacological mechanisms, clinical efficacy, future-oriented clinical approaches, and adverse effects. Efficacy for the shared indications of these drugs seems comparable. Differences among these drugs lie more in their adverse effect profiles. For example, lumateperone was found to have the lowest rate of weight gain while brexpiprazole was found to have the highest rate of weight gain associated with increased appetite. Aripiprazole had the lowest rates of extrapyramidal symptoms not including akathisia while cariprazine had the highest. All four agents reviewed have a variety of receptor affinities, which likely generates a variety of different adverse effects. This suggests that in any given patient, clinicians may see differential clinical effects.

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Evaluation of the Effect of Cariprazine on Memory and Cognition in Experimental Rodent Models

Cited by 4 publications

References 59 publications

Novel Multimodal Salicylamide Derivative with Antidepressant-like, Anxiolytic-like, Antipsychotic-like, and Anti-Amnesic Activity in Mice

Novel Multimodal Salicylamide Derivative with Antidepressant-like, Anxiolytic-like, Antipsychotic-like, and Anti-Amnesic Activity in Mice

Cariprazine: An Antipsychotic Medication with High Therapeutic Potential

Differentiating the third generation of antipsychotics: a focus on lumateperone’s similarities and differences

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