Antipsychotic- and anxiolytic-like properties of a multimodal compound JJGW08 in rodents

The takeaway

JJGW08, a novel arylpiperazine derivative, exhibits both antipsychotic and anxiolytic-like effects in rodents. With a multimodal receptor profile and good tolerability, it is a promising candidate for future drug development.

The science

JJGW08 primarily functions as an antagonist of dopamine D₂ and serotonin 5-HT_1A receptors, with milder effects on 5-HT_2A and 5-HT₇. In mice and rats, it reduced hyperlocomotion caused by MK-801 and amphetamine, behaviors linked to psychosis, without causing catalepsy or impairing motor coordination at effective doses. Notably, JJGW08 showed anxiolytic-like effects in both the four-plate and marble burying tests, demonstrating its effectiveness across different anxiety models. However, it did not improve prepulse inhibition deficits, indicating a limited effect on sensorimotor gating.

Why it matters

By combining antipsychotic and anxiolytic properties without significant motor side effects, JJGW08 emphasizes the potential of multimodal compounds as therapies. Studies in rodents that replicate these effects further support its promise as a candidate for advanced treatments of schizophrenia and anxiety.

Original article

https://doi.org/10.3390/ijms232415929