Transient receptor potential melastatin channel sensitive to praziquantel (TRPMPZQ)

The Transient receptor potential melastatin channel sensitive to praziquantel (TRPMPZQ) is the primary molecular target for the anthelmintic drug praziquantel in parasitic flatworms, including tapeworms and schistosomes (Park et al., 2019). For many years, the drug's mechanism was linked to voltage-gated calcium channels, specifically a variant beta subunit, but recent structural and genetic studies have identified TRPMPZQ as the definitive receptor (Le et al., 2021). This ion channel is crucial for maintaining calcium homeostasis, which regulates muscle contraction and the integrity of the parasite's protective outer layer, the tegument (Greenberg, 2005). Praziquantel acts as a potent agonist, binding to a hydrophobic pocket in the channel's voltage-sensor-like domain to induce a rapid and massive influx of calcium ions (Marchant et al., 2022). This influx causes immediate spastic paralysis and tegumental damage, leading to the parasite's detachment from host tissues and subsequent death (Park et al., 2019). In clinical practice, this target is exploited to treat infections such as schistosomiasis, taeniasis, and cysticercosis (CDC, 2024). However, the rapid death of parasites in sensitive areas like the central nervous system can trigger severe inflammatory responses, presenting a significant therapeutic challenge (StatPearls, 2023).

Other names

Praziquantel-sensitive Ca2+ entry pathwayVoltage-gated calcium channel subunit beta (variant)SmTRPMPZQTsTRPMPZQFlatworm calcium channel

Praziquantel acts as an allosteric activator of the TRPMPZQ channel, binding to a hydrophobic pocket within the voltage-sensor-like domain to trigger a massive influx of calcium ions, resulting in spastic paralysis and tegumental vacuolization.