The in vitro pharmacology of the beta-adrenergic receptor pet ligand (s)-fluorocarazolol reveals high affinity for cloned beta-adrenergic receptors and moderate affinity for the human 5-HT1A receptor

Psychopharmacology (Berl). 2001 Aug;157(1):111-4. doi: 10.1007/s002130100844.


Rationale: s-Fluorocarazolol [(S)-FCZ] is the major positron emission tomography (PET) ligand currently used to visualize central beta-adrenergic receptors in vivo, although its pharmacology is incompletely known.

Objective: Our objective was to comprehensively characterize the in vitro pharmacology of (S)- and (R)-FCZ to determine its suitability for study of central and peripheral beta-adrenergic receptors.

Methods: We characterized the in vitro pharmacology of (S)-FCZ at 42 biogenic amine receptors and transporters in vitro using the resources of the National Institute of Mental Health Psychoactive Drug Screening Program.

Results: As expected (R)- and (S)-FCZ had high affinities for beta-adrenergic receptors (Ki values=0.08-0.45 nM) and negligible affinities (Ki values>100 nM) for nearly all other tested receptors and transporters with the exception of the h5-HT1A receptor for which (S)-FCZ had high affinity (Ki=34 nM). Interestingly, (R)-FCZ had low affinity for the h5-HT1A receptor (Ki=342 nM).

Conclusion: The high affinity of (S)-FCZ for the h5-HT1A receptor is not likely to interfere with studies of peripheral beta-adrenergic receptors, since 5-HT1A receptors are expressed at very low levels outside the central nervous system. Indeed, computer simulations predict that even at low ligand concentrations, 5-HT1A binding in brain regions like hippocampus are likely to be substantial. Thus, (S)-FCZ may not be a suitable PET ligand for studies of central nervous system beta-adrenergic receptors unless the contribution by 5-HT1A sites can be shown to be negligible.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adrenergic beta-Antagonists / metabolism*
  • Carbazoles / metabolism*
  • Humans
  • Ligands
  • Propanolamines / metabolism*
  • Receptors, Adrenergic, beta / metabolism*
  • Receptors, Serotonin / metabolism*
  • Receptors, Serotonin, 5-HT1
  • Recombinant Proteins / metabolism
  • Stereoisomerism
  • Tomography, Emission-Computed*


  • Adrenergic beta-Antagonists
  • Carbazoles
  • Ligands
  • Propanolamines
  • Receptors, Adrenergic, beta
  • Receptors, Serotonin
  • Receptors, Serotonin, 5-HT1
  • Recombinant Proteins
  • fluorocarazolol