Purotoxins are a family of peptides found in spider venom that act on ionotropic purinergic receptors (P2X). The most studied members of the family, purotoxin-1 (PT1/FA001) and purotoxin-6 (PT6/FA006), selectively inhibit homomeric P2X3 receptors at nanomolar concentrations.
P2X receptors are ligand-gated ion channels activated by extracellular adenosine triphosphate (ATP). In humans, seven isoforms of P2X receptors are known, among which P2X3 receptors are almost exclusively expressed in sensory neurons and are involved in pain perception. They play an important role in pain related to osteoarthritis, bone cancer and bone tissue destruction, neuropathic pain in diabetes, trigeminal neuralgia, lower urinary tract symptoms, pain in endometriosis, migraine, pain in candidiasis, as well as chronic cough and hypertension. Progress in the development of drugs acting on purinergic receptors has been slow due to the lack of selective high-affinity inhibitors of homomeric P2X3 with acceptable pharmacokinetic parameters and bioavailability. Selectivity for homomeric P2X3 over heteromeric P2X2/3 receptors is important because the latter are expressed by neurons that innervate taste buds and treatment with nonselective inhibitors leads to taste disturbances in patients.