• MeSH
• Antipsychotic Agents * administration & dosage   therapeutic use   MeSH
• Aripiprazole administration & dosage   therapeutic use   MeSH
• Adult MeSH
• Administration, Intravenous MeSH
• Congresses as Topic MeSH
• Middle Aged MeSH
• Humans MeSH
• Drug Monitoring MeSH
• Schizophrenia * drug therapy   MeSH
• Patient Satisfaction * MeSH
• Dose-Response Relationship, Drug MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Case Reports MeSH

Dopamine type 2 receptors (D2Rs) constitute the main molecular target in the pharmacotherapy of schizophrenia. However, the second and third generation of antipsychotics comprises multi-target ligands, also binding serotonin type 3 receptors (5-HT3Rs) and other receptor classes as well. Here, we examined two experimental compounds (marked compound K1697 and K1700) from the group of 1,4-di-substituted aromatic piperazines, previously described in the study of Juza et al., 2021, and compared them with the chosen reference antipsychotic, aripiprazole. Their efficacy against schizophrenia-like behavior was tested in two different models of psychosis in the rat, induced by acute administration of either amphetamine (1.5 mg/kg) or dizocilpine (0.1 mg/kg), reflecting the dopaminergic and glutamatergic hypotheses of schizophrenia. The two models exhibited broadly similar behavioral manifestations: hyperlocomotion, disrupted social behavior and impaired prepulse inhibition of the startle response. However, they differed in their treatment responses as hyperlocomotion and prepulse inhibition deficit in the dizocilpine model were resistant to antipsychotic treatment, unlike the amphetamine model. One of the experimental compounds, K1700, ameliorated all the observed schizophrenia-like behaviors in the amphetamine model with an efficacy comparable to or greater than aripiprazole. Whereas social impairments caused by dizocilpine were strongly suppressed by aripiprazole, K1700 was less efficient. Taken together, K1700 showed antipsychotic properties comparable to those of aripiprazole, although the efficacy of the two drugs differed in specific domains of behavior and was also model-dependent. Our present results highlight the differences in these two schizophrenia models and their responsiveness to pharmacotherapy, and confirm compound K1700 as a promising drug candidate.

• MeSH
• Amphetamine MeSH
• Antipsychotic Agents * therapeutic use   MeSH
• Aripiprazole MeSH
• Quinolones * MeSH
• Dizocilpine Maleate MeSH
• Dopamine metabolism   MeSH
• Rats MeSH
• Psychotic Disorders * drug therapy   MeSH
• Receptors, Serotonin MeSH
• Dose-Response Relationship, Drug MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

Autoři prezentují svoje zkušenosti s emočně nestabilními adolescentními pacienty, s projevy sebepoškozování a suicidálního chování, případně dalšími psychopatologickými symptomy. Diskutují otázky osobnostního vývoje v adolescenci, rizikové okolnosti, které projevy emoční nestability zhoršují, a zabývají se možnostmi terapeutického ovlivnění.

The authors present their experiences with emotionally instable adolescent patients, with signs harm and suicidal behavior, possibly with other psychopatological symptoms. They discuss the issues of development in adolescence, risk circumstances that intensify the manifestations of emotional instability and discuss the possibilities of therapeutic influence.

• MeSH
• Aripiprazole therapeutic use   MeSH
• Fluoxetine therapeutic use   MeSH
• Borderline Personality Disorder * diagnosis   therapy   MeSH
• Family Conflict psychology   MeSH
• Humans MeSH
• Adolescent MeSH
• Suicide, Attempted * MeSH
• Quetiapine Fumarate therapeutic use   MeSH
• Self Mutilation therapy   MeSH
• Sertraline therapeutic use   MeSH
• Treatment Outcome MeSH
• Check Tag
• Humans MeSH
• Adolescent MeSH
• Male MeSH
• Female MeSH
• Publication type
• Case Reports MeSH

Aripiprazol patří do skupiny parciálních agonistů D2 receptorů. U dospělých je indikován k léčbě schizofrenie (SCH), k léčbě středně těžkých až těžkých manických epizod a k prevenci manické epizody u bipolární poruchy (BP). Přehled dvou kazuistik dokládá využití aripiprazolu v léčbě manické a smíšené epizody.

Aripiprazole belongs to the group of partial D2 receptor agonists. In adults, it is indicated for the treatment of schizophrenia (SCH), for the treatment of moderate to severe manic episodes, and for the prevention of manic episodes in bipolar disorder (BP). A review of two case reports illustrates the use of aripiprazole in the treatment of manic and mixed episodes.

• Keywords
• ABILIFY (aripiprazol), Aryzalera (aripiprazol),
• MeSH
• Affective Disorders, Psychotic diagnosis   drug therapy   MeSH
• Aripiprazole administration & dosage   pharmacology   MeSH
• Bipolar and Related Disorders diagnosis   drug therapy   MeSH
• Bipolar Disorder * diagnosis   drug therapy   MeSH
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Mania drug therapy   MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Publication type
• Case Reports MeSH

• MeSH
• Antipsychotic Agents * pharmacokinetics   therapeutic use   MeSH
• Aripiprazole pharmacokinetics   therapeutic use   MeSH
• Haloperidol pharmacokinetics   therapeutic use   MeSH
• Hippocampus drug effects   MeSH
• Clinical Trials as Topic MeSH
• Rats MeSH
• Brain-Derived Neurotrophic Factor drug effects   MeSH
• Prefrontal Cortex drug effects   MeSH
• Stress, Psychological drug therapy   MeSH
• Receptors, Glucocorticoid drug effects   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Animals MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH

Objective. Changes in the brain derived neurotrophic factor (BDNF) and glucocorticoid receptor (GR) expression in the prefrontal cortex (PFC) and hippocampus (HIP) are associated with psychiatric diseases and stress response. Chronic mild stress (CMS) may alter BDNF as well as GR levels in both the PFC and the HIP. The aim of the present study was to find out whether chronic treatment with a typical antipsychotic haloperidol (HAL) and an atypical antipsychotic aripiprazole (ARI) may modify the CMS effect on the BDNF and GR expression in the above-mentioned structures. Methods. The rats were exposed to CMS for 3 weeks and from the 7th day of CMS injected with vehicle (VEH), HAL (1 mg/kg) or ARI (10 mg/kg) for 4 weeks. BDNF and GR mRNA levels were established in the PFC and the HIP by Real Time PCR, whereas, PFC and HIP samples were obtained by punching them from 500 μm thick frozen sections. C-Fos immunoreactivity was analyzed in the PFC and the HIP on 30 μm thick paraformaldehyde fixed sections. Weight gain and corticosterone (CORT) levels were also measured. Results. The CMS and HAL suppressed the BDNF and GR mRNA levels in the PFC. In the HIP, CMS elevated BDNF mRNA levels that were suppressed by HAL and ARI treatments. The CMS decreased the c-Fos immunoreactivity in the PFC in both HAL- and ARI-treated animals. In the HIP, HAL increased the c-Fos immunoreactivity that was again diminished in animals exposed to CMS. Stressed animals gained markedly less weight until the 7th day of CMS, however, later their weight gain did not differ from the unstressed ones or was even higher in CMS+HAL group. Un-stressed HAL and ARI animals gained less weight than the VEH ones. Neither CMS nor HAL/ARI affected the plasma CORT levels. Conclusion. The present data indicate that HAL and ARI in the doses 1 mg/kg or 10 mg/kg, respectively, does not modify the effect of the CMS preconditioning on the BDNF and GR mRNA levels in the PFC or the HIP. However, HAL seems to modify the CMS effect on the HIP activation.

• MeSH
• Antipsychotic Agents * pharmacology   MeSH
• Aripiprazole pharmacology   MeSH
• Haloperidol * MeSH
• Hippocampus MeSH
• Rats MeSH
• Brain-Derived Neurotrophic Factor genetics   MeSH
• Prefrontal Cortex MeSH
• Receptors, Glucocorticoid genetics   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

In this pilot study, a series of new 3,4-dihydroquinolin-2(1H)-one derivatives as potential dopamine receptor D2 (D2R) modulators were synthesized and evaluated in vitro. The preliminary structure-activity relationship disclosed that compound 5e exhibited the highest D2R affinity among the newly synthesized compounds. In addition, 5e showed a very low cytotoxic profile and a high probability to cross the blood-brain barrier, which is important considering the observed affinity. However, molecular modelling simulation revealed completely different binding mode of 5e compared to USC-D301, which might be the culprit of the reduced affinity of 5e toward D2R in comparison with USC-D301.

• MeSH
• Aripiprazole chemical synthesis   pharmacology   MeSH
• Cell Death MeSH
• Central Nervous System drug effects   MeSH
• Quinolones chemical synthesis   chemistry   pharmacology   MeSH
• CHO Cells MeSH
• Cricetulus MeSH
• Blood-Brain Barrier drug effects   pathology   MeSH
• Ligands MeSH
• Models, Molecular MeSH
• Drug Design MeSH
• Receptors, Dopamine D2 chemistry   metabolism   MeSH
• Binding Sites MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

• MeSH
• Antipsychotic Agents administration & dosage   adverse effects   therapeutic use   MeSH
• Aripiprazole administration & dosage   pharmacokinetics   therapeutic use   MeSH
• Ciprofloxacin pharmacokinetics   adverse effects   MeSH
• Adult MeSH
• Hematopoiesis drug effects   MeSH
• Catatonia MeSH
• Clozapine * administration & dosage   adverse effects   therapeutic use   MeSH
• Delayed-Action Preparations therapeutic use   MeSH
• Leukocytes drug effects   MeSH
• Humans MeSH
• Lithium therapeutic use   MeSH
• Neutropenia * chemically induced   physiopathology   prevention & control   MeSH
• Schizophrenia, Catatonic drug therapy   complications   MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Male MeSH
• Publication type
• Case Reports MeSH

• MeSH
• Amisulpride administration & dosage   therapeutic use   MeSH
• Antipsychotic Agents administration & dosage   therapeutic use   MeSH
• Aripiprazole administration & dosage   therapeutic use   MeSH
• Adult MeSH
• Fluphenazine administration & dosage   therapeutic use   MeSH
• Clozapine administration & dosage   therapeutic use   MeSH
• Middle Aged MeSH
• Humans MeSH
• Schizophrenia, Paranoid diagnosis   drug therapy   complications   MeSH
• Psychotherapy MeSH
• Psychotic Disorders diagnosis   drug therapy   pathology   MeSH
• Schizophrenia Spectrum and Other Psychotic Disorders * diagnosis   drug therapy   physiopathology   MeSH
• Schizophrenia diagnosis   drug therapy   physiopathology   MeSH
• Schizotypal Personality Disorder diagnosis   drug therapy   MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Case Reports MeSH

Aripiprazol, brexpiprazol a kariprazin patří do skupiny parciální agonistů dopaminových receptorů (DRPA), subkategorie antipsychotik druhé generace. Na první pohled mohou vypadat podobně. Jsou mezi nimi ale klíčové odlišnosti týkající se farmakodynamiky, farmakokinetiky, lékových interakcí, účinnosti, bezpečnosti a snášenlivosti, indikací, dávkování, lékových forem a dalších faktorů souvisejících s jejich úspěšným použitím.

Aripiprazole, brexpiprazole, and cariprazine constitute the DRPA (dopamine receptor partial agonists) subcategory of second-generation antipsychotics. Seemingly, they appear to be similar. However, they differ significantly in their pharmacodynamics, pharmacokinetics, drug interactions, efficacy, safety and tolerability, approved indications, dosing, formulations, and other factors related their use.

• Keywords
• kariprazin, brexpiprazol,
• MeSH
• Dopamine Agonists * pharmacokinetics   pharmacology   therapeutic use   MeSH
• Antipsychotic Agents pharmacokinetics   pharmacology   therapeutic use   MeSH
• Aripiprazole pharmacokinetics   pharmacology   therapeutic use   MeSH
• Bipolar Disorder drug therapy   MeSH
• Depressive Disorder drug therapy   MeSH
• Humans MeSH
• Schizophrenia drug therapy   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH