Pimavanserin tartrate

Shi M, et al. Neuropharmacology, 2021, 201, 108838.

Pimavanserin tartrate exhibits significant therapeutic potential in mitigating prepulse inhibition (PPI) deficits commonly associated with neuropsychiatric disorders. This study evaluated the compound's efficacy and identified the neural mechanisms and critical brain regions mediating its effects.
Intraperitoneal administration of pimavanserin tartrate enhanced normal PPI behavior and reversed deficits induced by the nonselective dopamine D1/D2 receptor agonist pergolide. Targeted infusions into the nucleus accumbens and ventral hippocampus successfully reversed PPI impairments, whereas similar interventions in the medial prefrontal cortex or ventral tegmental area did not yield comparable results. These findings highlight the nucleus accumbens and ventral hippocampus as pivotal brain regions responsible for the antipsychotic effects of pimavanserin tartrate. The study underscores the utility of pimavanserin tartrate in dissecting the molecular and neural mechanisms underlying 5-HT2A receptor-modulated neural circuits.

Ramachandran S, et al. Molecular Therapy-Oncolytics, 19, 19-32.

Pimavanserin tartrate (PVT) has demonstrated significant potential as an anticancer agent against pancreatic cancer. In recent studies, PVT selectively suppressed the proliferation and induced apoptosis in various pancreatic cancer cells, including gemcitabine-resistant strains, while exhibiting minimal cytotoxicity to normal pancreatic epithelial cells and lung fibroblasts.
Mechanism of Action: The growth-inhibitory and pro-apoptotic effects of PVT are mediated through the inhibition of the Akt/Gli1 signaling axis, a critical pathway in cancer cell survival and proliferation. This mechanism underscores its potential in targeting drug-resistant cancer phenotypes, offering a novel approach to overcoming chemoresistance in pancreatic malignancies.
In Vivo Efficacy: Oral administration of PVT significantly suppressed pancreatic tumor xenografts in both subcutaneous and orthotopic mouse models, achieving tumor growth inhibition rates ranging from 51% to 77%. Importantly, chronic administration of PVT displayed no observable toxicity or behavioral abnormalities in animal models, reinforcing its safety profile.
Given its established safety and efficacy in preclinical models, PVT represents a valuable candidate for repurposing as a therapeutic agent for pancreatic cancer.

Zhang Y, et al. Biomedicine & Pharmacotherapy, 2023, 168, 115665.

Pimavanserin tartrate (PVT) has emerged as a promising candidate in oncology, demonstrating potent anticancer activities in pancreatic cancer and triple-negative breast cancer (TNBC).
Pancreatic Cancer Applications: PVT suppresses pancreatic cancer growth by inhibiting the Akt/Gli1 signaling axis, effectively inducing apoptosis and curbing proliferation. In vivo studies reported tumor suppression rates between 51% and 77% in xenograft models, with minimal toxicity to normal cells and no adverse behavioral effects. These findings support its rapid clinical repurposing for pancreatic cancer therapy.
Triple-Negative Breast Cancer (TNBC) Applications: In TNBC cells, PVT triggers mitochondria-dependent intrinsic apoptosis while promoting cytoprotective autophagy via the PI3K/Akt/mTOR pathway. Moreover, PVT exhibits strong synergistic effects with doxorubicin, significantly enhancing TNBC cell sensitivity to chemotherapy. In vivo, PVT demonstrated moderate efficacy in reducing subcutaneous TNBC tumor growth, underscoring its potential as a combinatory therapeutic strategy.