ArticlePharmacological reports : PR2025
Compound PZ-1262, a 4-isoquinoline-sulfonamide analog of Brexpiprazole, produces potential antidepressant, anxiolytic and procognitive effects in rodent models.
Article in Pharmacological reports : PR, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Not yet cited in PubMed.
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Corrections and comments
- Erratum issued
Authors and funding
14 authors.
Funding
Abstract
backgroundNovel antipsychotics are characterized by multitarget profile of action, affecting among others, dopamine and serotonin receptors. In a series of experiments, we designed, synthesized and examined two new isoquinoline-sulfonamide analogs of the modern multitarget antipsychotics aripiprazole and brexpiprazole, compounds PZ-1262 and PZ-1264. We hypothesized that the 4-isoquinolinesulfonamide moiety, derived from the structure of 5-HT
methodsThe receptor binding profile, functional activity, and metabolic stability of PZ-1262 and PZ-1264 were evaluated through in vitro assays. Potential antipsychotic, antidepressant, anxiolytic, and pro-cognitive effects were assessed using in vivo behavioral tests in rodents.
resultsIn vitro, PZ compounds demonstrated partial agonistic activity at 5-HT
conclusionsThe complex pharmacodynamic profile translated into the useful psychotropic effects. While the compounds potentiated D-amphetamine- and phencyclidine-induced hyperactivity, this action could be regarded as a desired activating effect rather than evidence against antipsychotic-like efficacy. Present findings point to PZ-1262 as a more promising lead compound for further research.
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