β-blocker binding to human 5-HT1A receptors in vivo and in vitro:: Implications for antidepressant therapy

A novel strategy for improving the treatment of depressive illness is augmentation of antidepressants with a 5-HT1(1A) autoreceptor antagonist. However, trials using the 5-HT1(1A)/beta-blocker pindolol are proving inconsistent. We report how positron emission tomography (PET) and in vitro autoradiography can inform trials of antidepressant augmentation. We show that in healthy volunteers, in vivo, pindolol (n = 10) and penbutolol (n = 4), but not tertatolol (n = 4) occupy the human 5-HT1A receptors, at clinical doses. Pindolol, as well as the beta-blockers penbutolol and tertatolol, has high affinity for human 5-HT1A receptors in post-mortem brain slices (n = 4). Pindolol shows preference for 5-HT1A autoreceptors versus the post-synaptic receptors both in vitro and in vivo. Our data reveal that pindolol doses used in antidepressant trials so far are suboptimal for significant occupancy at the 5-HT1A autoreceptor. Penbutolol or higher doses of pindolol are candidates for testing as antidepressant augmenting regimes in future clinical trials. (C) 2000 American College of Neuropsychopharmacology. Published by Elsevier Science Inc. All rights reserved.