BEHAVIORAL AND PHARMACOLOGICAL PROFILING OF NOVEL MULTIMODAL COMPOUNDS ADDRESSING PSYCHOSIS-RELATED SYMPTOMS AND COGNITIVE IMPAIRMENT

Schizophrenia is a severe neuropsychiatric disorder characterized by disruptions in perception, emotional expression, and cognition. Currently available antipsychotics alleviate positive symptoms but lack similar efficacy in relieving memory and learning deficits. Moreover, affective and anxiety symptoms frequently co-occur, further contributing to functional impairment. Therefore, the development of novel drug candidates remains essential. This study evaluated the potential antipsychotic- and antiamnesic-like properties of a novel group of biologically active compounds, along with their potential antidepressant- and anxiolytic-like effects. We investigated the intrinsic activities of the compounds MG-7, PY-1, PY-2, PY-3, and PY-7 towards D₂ and 5-HT₇ receptors. We then conducted a behavioral test battery comprising spontaneous locomotor activity, elevated plus maze, and tail suspension tests, followed by MK-801-induced hyperlocomotion, object recognition, and passive avoidance tasks. MK-801 was administered at 0.2 mg/kg to induce hyperlocomotion and 0.125 mg/kg to induce memory impairment. All experiments were performed on C57BL/6 male mice, with lurasidone as a reference compound. Functional assays revealed antagonistic activity at 5-HT₇ receptors, while preliminary profiling at D₂ receptors indicated heterogeneous functional responses. MG-7, PY-2, PY-3, PY-7, and lurasidone exhibited potential antipsychotic-like activity. In the object recognition test, only PY-2 attenuated the MK-801-induced memory deficits. None of the tested compounds improved MK-801-induced impairments in associative memory in the passive avoidance task, except lurasidone. No antidepressant- or anxiolytic-like effects were observed. Among the evaluated compounds, PY-2 demonstrated the most favorable pharmacological profile, supporting its selection for further studies targeting positive symptoms and cognitive impairments associated with schizophrenia.