Adrenergic receptor function in panic disorder -: I.: Platelet α2 receptors:: Gi protein coupling, effects of imipramine, and relationship to treatment outcome

Various studies suggest alpha(2)-adrenergic receptor (alpha(2)AR) dysregulation in panic disorder (PD). Platelet alpha(2)-AR exist in high- and low-conformational states as a function of their coupling to G(i) protein, alpha(2)-AR coupling is important in signal transduction and is modulated by antidepressants. alpha(2)AR density in the high- and low-conformational states, agonist affinity, and coupling efficiency were investigated in 21 healthy controls, 21 drug-free PD patients, and eight imipiramine-treated patients using norepinephrine displacement of H-3-yohimbine binding. Percentage of receptors in the high-conformational state (%R-H) and the ratio of the agonist dissociation constant to the receptor in the low-/high-conformational state (K-L/K-H), calculated from displacement experiments, were used as coupling indices. Patients had high alpha(2)AR density in both conformational states. %R-H and K-L/K-H ratio were significantly different, particularly in patients with Hamilton scale for depression (HAMD) scores greater than or equal to 15, Imipramine treatment (29 weeks) had no effect on alpha(2)AR density or coupling, despite improvement in anxiety ratings. High pretreatment alpha(2)AR density and coupling predicted low severity of anxiety after treatment. Increased alpha(2)AR density and abnormal coupling may represent an adaptive mechanism or trait marker in PD. [Neuropsychopharmacology 20:162-276, 1999] (C) 1998 American College of Neuropsychopharmacology.