The purinergic P2X3 subtype is an ATP-gated ion channel mainly expressed in pain sensory neurons and thought to mediate nociception especially in conditions like neuropathic pain and migraine. On these bases, this P2X receptor subtype is considered as a potential target for the development of new analgesic drugs. Since non-nucleotide diamino-pyrimidine derivatives were recently reported to block P2X3 receptors with high potency [1], a new series of P2X3 ligands was designed considering the structure of the aforementioned pyrimidines and molecular modeling data obtained by comparing pyrimidine and purine scaffolds. Hence, purine derivatives bearing different substituents in 9-position were synthesized and evaluated for their potential antagonist activity. In particular, the new compounds were tested to explore their potential activity on HEK293 cells expressing rat P2X3 receptors. The effects mediated by this P2X receptor subtype were recorded, under voltage clamp, as inward currents evoked by the full agonist alpha,beta-meATP using the patch-clamp technique. Data show that these new compounds blocked responses mediated by P2X3 receptor activation.

Substituted adenine derivatives as novel P2X3 receptor ligands

DAL BEN, DIEGO;LAMBERTUCCI, Catia;MARUCCI, Gabriella;VOLPINI, Rosaria;CRISTALLI, Gloria
2010

Abstract

The purinergic P2X3 subtype is an ATP-gated ion channel mainly expressed in pain sensory neurons and thought to mediate nociception especially in conditions like neuropathic pain and migraine. On these bases, this P2X receptor subtype is considered as a potential target for the development of new analgesic drugs. Since non-nucleotide diamino-pyrimidine derivatives were recently reported to block P2X3 receptors with high potency [1], a new series of P2X3 ligands was designed considering the structure of the aforementioned pyrimidines and molecular modeling data obtained by comparing pyrimidine and purine scaffolds. Hence, purine derivatives bearing different substituents in 9-position were synthesized and evaluated for their potential antagonist activity. In particular, the new compounds were tested to explore their potential activity on HEK293 cells expressing rat P2X3 receptors. The effects mediated by this P2X receptor subtype were recorded, under voltage clamp, as inward currents evoked by the full agonist alpha,beta-meATP using the patch-clamp technique. Data show that these new compounds blocked responses mediated by P2X3 receptor activation.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11581/250540
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