Purines P1 receptor agonists

The systemic or spinal administration of adenosine (ADO) or ADO A1 receptor selective agonists has been shown to provide clinically effective analgesia.93 However, analgesic efficacy of systemically administered ADO in neuropathic pain patients has been variable.94 In contrast, intrathecal injection of ADO or an A1 receptor agonist appears to consistently reduce pathological pain in neuropathic subjects or in healthy volunteers given intradermal capsaicin to induce central sensitization.95-97 Despite these promising results, their profound effects on cardiovascular function have hampered the development of ADO receptors agonists as analgesics.

Inhibition of the primary metabolic enzyme, adenosine kinase (AK), which regulates ADO availability enhances the beneficial actions of adenosine at sites of tissue injury or trauma and AK inhibitors are potent antinociceptive and anti-inflammatory agents with an potentially improved therapeutic window over direct acting ADO receptor agonists.98 ABT-702 (Figure 12), a non-nucleoside AK inhibitor, has both analgesic (e.g., effective in acute nociception) and antihyperalgesic activity (e.g., effective in blocking both hyperalgesia and allodynia).98 The analgesic actions of ABT-702 are blocked by selectivity ADO A1 receptor subtype antagonists and the locus of analgesic activity is in the spinal cord.98 ABT-702 also shows significantly greater separation between its antihyperalgesic activity and its effects on CNS or cardiovascular function as compared to direct-acting ADO receptor agonists. P2 receptor antagonists

The cloning and characterization of the family of ATP-sensitive ligand-gated ion channels (P2X receptors) provided mechanistic insights for the role of ATP as an extracellular signaling molecule.99 The P2X3 channel is localized

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Peripheral Neuropathy Natural Treatment Options

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