Targeting neuronal adenylyl cyclase for the treatment of chronic pain

Drug Discov Today. 2012 Jun;17(11-12):573-82. doi: 10.1016/j.drudis.2012.01.009. Epub 2012 Jan 26.

Abstract

Pain research is currently undergoing dramatic changes. In the area of basic pain research, new discoveries have been made towards the understanding of pain transmission, modulation and plasticity. However, many of these basic discoveries have not yet led to the development of new drugs for the treatment of chronic pain. One major reason for this disconnection is the lack of translational research and drug discovery based directly on the novel pain mechanism. In this review, I focus on activity-dependent potentiation in pain-related cortical areas and recent translational research on adenylyl cyclase subtype 1 (AC1) as a novel target for treating chronic pain. In particular, I discuss the AC1 inhibitor, NB001, which produces powerful analgesic effects in animal models of chronic pain by inhibiting chronic pain-related cortical potentiation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adenosine Triphosphate / analogs & derivatives*
  • Adenosine Triphosphate / pharmacology
  • Adenosine Triphosphate / therapeutic use
  • Adenylyl Cyclase Inhibitors*
  • Adenylyl Cyclases
  • Analgesics / pharmacology
  • Analgesics / therapeutic use*
  • Animals
  • Cerebral Cortex / drug effects
  • Chronic Pain / drug therapy*
  • Chronic Pain / enzymology
  • Chronic Pain / etiology
  • Chronic Pain / genetics
  • Drug Discovery
  • Humans
  • Long-Term Potentiation / drug effects
  • Molecular Targeted Therapy
  • Neurons / drug effects*
  • Neurons / enzymology
  • Synaptic Potentials / drug effects

Substances

  • 5-((2-(6-Amino-9H-purin-9-yl) ethyl) amino)-1-pentanol
  • Adenylyl Cyclase Inhibitors
  • Analgesics
  • Adenosine Triphosphate
  • Adenylyl Cyclases
  • adenylyl cyclase 1