Selective activation of Gαob by an adenosine A₁ receptor agonist elicits analgesia without cardiorespiratory depression.

ABSTRACT: The development of therapeutic agonists for G protein-coupled receptors (GPCRs) is hampered by the propensity of GPCRs to couple to multiple intracellular signalling pathways. This promiscuous coupling leads to numerous downstream cellular effects, some of which are therapeutically undesirable. This is especially the case for adenosine A₁ receptors (A₁Rs) whose clinical potential is undermined by the sedation and cardiorespiratory depression caused by conventional agonists. We have discovered that the A₁R-selective agonist, benzyloxy-cyclopentyladenosine (BnOCPA), is a potent and powerful analgesic but does not cause sedation, bradycardia, hypotension or respiratory depression. This unprecedented discrimination between native A₁Rs arises from BnO

SUBMITTER: Wall MJ 

PROVIDER: S-EPMC9293909 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature