%0 Journal Article
%T Selective Adenylyl Cyclase Type 1 Inhibitors as Potential Opioid Alternatives For Chronic Pain
%A Val J Watts
%J Archive of "Neuropsychopharmacology".
%D 2018
%R 10.1038/npp.2017.190
%X Chronic pain is a major health concern that costs the US more than $635 billion per year (Gaskin and Richard, 2012). The drugs used for the management of chronic pain include opioid analgesics, neuronal stabilizers such as anticonvulsants, and antidepressants. Opioids are the most widely used analgesics; however, there are significant problems associated with long-term opioid therapy for chronic pain, including diversion and addiction (Volkow and McLellan, 2016). Moreover, the pharmaceutical industry has retreated from studying novel pain therapeutics due to the enormous risk and low probability of success that reflect in part, a lack of predictive animal models and biomarkers (Skolnick and Volkow, 2016). These observations indicate an essential need for academic investigators to identify new agents acting on unique targets in the war on chronic pain. Neurobiological, genetic, and preclinical studies have implicated neuronal adenylyl cyclase type 1 (AC1) as a potential new target (Zhuo, 2012). Adenylyl cyclases (AC) are members of an enzyme family that serve as effectors for numerous G-protein-coupled receptors (for example, opioid receptors) and produce the second messenger cAMP from ATP. The nine membrane-bound isoforms of AC share a similar structure and each is uniquely regulated by G protein subunits, Ca2+, protein kinases, and subcellular localization (Dessauer et al, 2017). Membrane-bound ACs are highly expressed in the central nervous system and generally have overlapping expression patterns. Animals lacking one or multiple AC isoforms have been essential tools to inform on the physiological roles of AC signaling in the central nervous system
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5719099/