Volume 64, Issue 2 p. 77-81
SPECIAL ISSUE ARTICLE

Radiolabeled HOCPCA as a highly useful tool in drug discovery and pharmacology

Nane Griem-Krey

Nane Griem-Krey

Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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Bente Frølund

Bente Frølund

Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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Aleš Marek

Corresponding Author

Aleš Marek

Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Prague, Czech Republic

Correspondence

Aleš Marek, Radiochemistry, Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Fleming sq. 542/2, 160 00 Prague 6, Czech Republic.

Email: [email protected]

Petrine Wellendorph, Pharmacology, Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, 2100 Copenhagen, Denmark.

Email: [email protected]

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Petrine Wellendorph

Corresponding Author

Petrine Wellendorph

Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

Correspondence

Aleš Marek, Radiochemistry, Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Fleming sq. 542/2, 160 00 Prague 6, Czech Republic.

Email: [email protected]

Petrine Wellendorph, Pharmacology, Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, 2100 Copenhagen, Denmark.

Email: [email protected]

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First published: 20 July 2020

Abstract

GHB (γ-hydroxybutyrate) is not only an endogenously present small molecule but also a clinically prescribed drug for the symptomatic treatment of narcolepsy. However, GHB's mechanism of action remains to be uncovered. Within the CNS, GHB targets both GABAB receptors and a pharmacologically distinct population of high-affinity binding sites with unknown molecular identity. HOCPCA (3-hydroxycyclopent-1-enecarboxylic acid) is a structural analog of GHB selectively targeting GHB high-affinity binding sites. Here, we discuss the usefulness of 3H- and 11C-labeled HOCPCA as radioligands for selectively probing GHB high-affinity binding sites and their application in drug discovery. As such, [3H]HOCPCA's exceptional affinity and selectivity makes it an indispensable tool in drug discovery, and its utility has been demonstrated in, for example, homogenate binding studies, in vitro as well as ex vivo autoradiography. Moreover, the successful synthesis of [11C]HOCPCA is a starting point for further ligand development for future in vivo investigations of GHB high-affinity binding sites.

CONFLICT OF INTEREST

The authors declare no competing interests.