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, 157 (1), 111-4

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

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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

B L Roth et al. Psychopharmacology (Berl).

Abstract

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.

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