beta-blocker binding to human 5-HT(1A) receptors in vivo and in vitro: implications for antidepressant therapy.

Article Details

Citation

Copy to clipboard

Rabiner EA, Gunn RN, Castro ME, Sargent PA, Cowen PJ, Koepp MJ, Meyer JH, Bench CJ, Harrison PJ, Pazos A, Sharp T, Grasby PM

beta-blocker binding to human 5-HT(1A) receptors in vivo and in vitro: implications for antidepressant therapy.

Neuropsychopharmacology. 2000 Sep;23(3):285-93.

PubMed ID

10942852 [ View in PubMed

]

Abstract

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-HT(1A) receptors, at clinical doses. Pindolol, as well as the beta-blockers penbutolol and tertatolol, has high affinity for human 5-HT(1A) receptors in post-mortem brain slices (n = 4). Pindolol shows preference for 5-HT(1A) 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-HT(1A) autoreceptor. Penbutolol or higher doses of pindolol are candidates for testing as antidepressant augmenting regimes in future clinical trials.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Penbutolol	5-hydroxytryptamine receptor 1A	Protein	Humans	Yes	Antagonist	Details