Pirenzepine (LS 519 free base) is a selective antagonist of the M1 muscarinic acetylcholine receptor (mAChR) that effectively inhibits gastric acid secretion and reduces muscle spasm, making it valuable for investigating peptic ulcers. Additionally, Pirenzepine exhibits anti-proliferative activity against cancer cells [1] [2].

Pirenzepine, administered at concentrations ranging from 100 to 140 μg/mL for a duration of 24 hours, effectively inhibits the proliferation of PC-3 cells. Furthermore, at a concentration of 110 μg/mL over the same time period, it suppresses migration in both prostate and lung cancer cells. The compound also decreases GLI1 expression in PC-3 cells when applied between 100 to 130 μg/mL across varying durations up to 24 hours. Detailed assays confirm Pirenzepine's action: In cell proliferation assays, it restricts the growth of PC-3 cells in a concentration-dependent manner; cell migration assays exhibit its ability to prevent the movement of PC-3 and A549 cell lines; and biochemical analysis reveals its inhibition of GLI1 and PTCH1 protein expression. RT-PCR data further supports the downregulation of GLI1 mRNA, a modulation of PTCH1 mRNA that did not achieve statistical significance, and no alteration in SHH mRNA expression, firmly establishing Pirenzepine's multifaceted inhibitory effects on cancer cell functionalities.

Pirenzepine treatment, administered as a single intraperitoneal injection at a dosage of 0.3 mg/kg, demonstrates advantageous effects in mitigating lipopolysaccharide (LPS)-induced septic shock in male C57BL/6 mice suffering from experimental endotoxemia. This treatment not only improved the survival rate in the context of LPS-induced septic shock but also alleviated pulmonary and hepatic injuries associated with the condition. Furthermore, it significantly reduced the expression of suppressor of cytokine signaling 3 (SOCS3) at the mRNA level.