A Review of Advances in Bioanalytical Methods for the Detection and Quantification of Olanzapine and Its Metabolites in Complex Biological Matrices.

Schizophrenia is a serious mental disorder that significantly affects the social and professional life of patients, causing distortion of reality and loss of identity and cognitive abilities. Psychopharmacological treatment is an integral part of modern psychiatry, and the introduction of new "atypical" antipsychotic drugs has brought significant progress in the treatment of this disorder. One of these drugs is olanzapine, which has an effective effect on the productive symptoms of schizophrenia while having an almost minimal potential to cause extrapyramidal syndrome. However, its effectiveness is confronted with frequent side effects, referred to as "metabolic disorders". Therefore, to ensure the effectiveness of treatment and to minimize the side effects caused by olanzapine, it is recommended to monitor the drug level during therapy. This article reviews the bioanalytical methodologies that enable efficient extraction and sensitive analysis of olanzapine. We considered the advantages and disadvantages of different sample pretreatment methods, including traditional and novel strategies. The analytical conditions required for the separation and detection of olanzapine and its metabolites were analyzed using chromatographic methods combined with various detectors.

Antipsychotic- and Anxiolytic-like Properties of a Multimodal Compound JJGW08 in Rodents.

Schizophrenia is a chronic mental illness, which remains difficult to treat. A high resistance to the available therapies, their insufficient efficacy, and numerous side effects are the reasons why there is an urgent need to develop new antipsychotics. This study aimed to assess the antipsychotic-like effects of JJGW08, a novel arylpiperazine alkyl derivative of salicylamide, in rodents. First, considering the JJGW08 receptor profile, we investigated the compound's intrinsic activity towards dopamine D2 and serotonin 5-HT1A, 5-HT2A, and 5-HT7 receptors using functional assays. Next, we assessed the effect of JJGW08 on MK-801- and amphetamine-induced hyperlocomotion, its risk of inducing catalepsy and impairing motor coordination, as well as the anxiolytic-like effects in the four-plate and marble burying tests in mice. Finally, we investigated the antipsychotic-like properties of JJGW08 in rats using MK-801-induced hyperlocomotion and prepulse inhibition tests. We found that JJGW08 showed antagonistic properties at dopamine D2 and serotonin 5-HT1A, 5-HT2A, and 5-HT7 receptors. However, the effect on the 5-HT2A and 5-HT7 receptors was very weak. Moreover, the tested compound showed an antipsychotic-like effect in MK-801- and amphetamine-induced hyperlocomotion but not in a prepulse inhibition test in rats. Notably, JJGW08 demonstrated anxiolytic-like properties in both behavioral tests. Importantly, the compound did not induce catalepsy or motor coordination impairment in mice at antipsychotic-like doses. Our study suggests it is worth searching for new potential antipsychotics among arylpiperazine alkyl derivatives of salicylamide.

Spontaneous head twitches in aged rats: behavioral and molecular study.

RATIONALE: We have discovered that rats at the age of 18 months begin to twitch their heads spontaneously (spontaneous head twitching, SHT). To date, no one has described this phenomenon. OBJECTIVES: The purpose of this study was to characterize SHT pharmacologically and to assess some possible mechanisms underlying SHT. METHODS: Wistar male rats were used in the study. Animals at the age of 18 months were qualified as HSHT (SHT ≥ 7/10 min observations) or LSHT (SHT < 7/10 min observations). Quantitative real-time PCR with TaqMan low-density array (TLDA) approach was adopted to assess the mRNA expression of selected genes in rat's hippocampus. RESULTS: HSHT rats did not differ from LSHT rats in terms of survival time, general health and behavior, water intake, and spontaneous locomotor activity. 2,5-dimethoxy-4-iodoamphetamine (DOI) at a dose of 2.5 mg/kg increased the SHT in HSHT and LSHT rats, while ketanserin dose-dependently abolished the SHT in the HSHT rats. The SHT was reduced or abolished by olanzapine, clozapine, risperidone, and pimavanserin. All these drugs have strong 5-HT2A receptor-inhibiting properties. Haloperidol and amisulpride, as antipsychotic drugs with a mostly dopaminergic mechanism of action, did not influence SHT. Similarly, escitalopram did not affect SHT. An in-depth gene expression analysis did not reveal significant differences between the HSHT and the LSHT rats. CONCLUSIONS: SHT appears in some aging rats (about 50%) and is permanent over time and specific to individuals. The 5-HT2A receptor strongly controls SHT. HSHT animals can be a useful animal model for studying 5-HT2A receptor ligands.

Searching for new drugs for the treatment of dementia-related psychosis.

Purpose: Along with the aging process, we can observe a deterioration of cognitive functions with the simultaneous occurrence of behavioural and psychological symptoms in the elderly population. Dementia with accompanying psychosis is becoming a growing problem, not only in medical but also in social terms. This article focuses on the issues related to the occurrence of psychosis in dementia, and the need to develop new treatment. Views: Psychosis in the elderly is different from that occurring with schizophrenia, as it is characterized by a different course and frequent resistance to treatment. In case of elderly patients, psychosis is probably associated with dysregulation of the serotonergic system. Due to the difficulties in using pharmacology in this age group, it is very important to individualize treatment. Antipsychotics are the main treatment used but they have many side effects, so in fact there is a lack of effective and safe solutions. Although pimavanserin is considered to be an effective alternative in the treatment of psychosis, it also carries a higher risk of mortality in this age group. Conclusions: The search for new, effective and safer drugs in the treatment of dementia-related psychosis works in many directions. New animal models are emerging that allow the screening of various drug "candidates". The available research suggests that the serotoninergic system is a good direction for the search for new therapeutic solutions. As the number of elderly people with dementia increases, there is a great medical need to make it easier for them and their caregivers to function.

Individualization of lithium therapy based on the monitoring of its level in saliva.

Purpose: Bipolar disorder (BD) is a mental disorder that affects approximately 2-3% of the population. The mainstay of treatment in bipolar disorder is lithium, which has also found an important application in the potentiation of antidepressants in drug-resistant depression, in the course of both bipolar disorder and recurrent depressive disorders. Views: The narrow therapeutic range of lithium and the frequent side effects it causes necessitates the monitoring of its concentration in the blood, which requires the periodic presence of the patient in a clinical laboratory. This is costly and inconvenient for patients, and is a common obstacle for psychiatrists who are reluctant to prescribe this effective drug precisely because of the inconvenience of having to monitor blood levels. If regular monitoring of lithium levels could be carried out without the need to puncture the vein and visit a clinic it would save time for both patients and healthcare professionals, avoid discomfort, and make difficult-to-reach patients easier to manage. Conclusions: Saliva in the monitoring of the lithium level is a promising biological material and offers the possibility to quickly estimate the individual lithium dosage for a specific patient which will provide the required therapeutic level. Saliva can be collected at home without the involvement of qualified personnel. Providing a more convenient and effective means of monitoring lithium therapy (e.g. the proposed non-invasive saliva level test) would enable safer, more effective therapy (more likely to maintain therapeutic blood levels) and an individualized therapeutic approach to a patient.