DOI: 10.1046/j.1471-4159.2000.0742597.x. Structure—Activity Relationships Among <i>N</i>‐Arachidonylethanolamine (Anandamide) Head Group Analogues for the Anandamide Transporter

Structure—Activity Relationships Among N‐Arachidonylethanolamine (Anandamide) Head Group Analogues for the Anandamide Transporter

10.1046/j.1471-4159.2000.0742597.x

Crossref journal-article

Wiley

Journal of Neurochemistry (311)

Abstract

Abstract: Two putative endocannabinoids, N‐arachidonylethanolamine (AEA) and 2‐arachidonylglycerol, are inactivated by removal from the extracellular environment by a process that has the features of protein‐mediated facilitated diffusion. We have synthesized and studied 22 N‐linked analogues of arachidonylamide for the purpose of increasing our understanding of the structural requirements for the binding of ligands to the AEA transporter. We have also determined the affinities of these analogues for both the CB1 cannabinoid receptor and fatty acid amide hydrolase (FAAH). We have identified several structural features that enhance binding to the AEA transporter in cerebellar granule cells. We have confirmed the findings of others that replacing the ethanolamine head group with 4‐hydroxybenzyl results in a high‐affinity ligand for the transporter. However, we find that the same molecule is also a competitive inhibitor of FAAH. Similarly, replacement of the ethanolamine of AEA with 3‐pyridinyl also results in a high‐affinity inhibitor of both the transporter and FAAH. We conclude that the structural requirements for ligand binding to the CB1 receptor and binding to the transporter are very different; however, the transporter and FAAH share most, but not all, structural requirements.

Bibliography

Jarrahian, A., Manna, S., Edgemond, W. S., Campbell, W. B., & Hillard, C. J. (2000). StructureâActivity Relationships Among NâArachidonylethanolamine (Anandamide) Head Group Analogues for the Anandamide Transporter. Journal of Neurochemistry, 74(6), 2597â2606. Portico.

Authors 5

Abbas Jarrahian (first)
Sukumar Manna (additional)
William S. Edgemond (additional)
William B. Campbell (additional)
Cecilia J. Hillard (additional)

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Dates

Type	When
Created	22 years, 5 months ago (March 12, 2003, 1:46 a.m.)
Deposited	1 year, 10 months ago (Oct. 29, 2023, 9:19 a.m.)
Indexed	4 months, 4 weeks ago (March 31, 2025, 3:23 a.m.)
Issued	25 years, 2 months ago (June 6, 2000)
Published	25 years, 2 months ago (June 6, 2000)
Published Online	23 years, 7 months ago (Jan. 18, 2002)
Published Print	25 years, 2 months ago (June 6, 2000)

Funders 0

None

BibTeX

@article{Jarrahian_2000, title={Structure—Activity Relationships Among N‐Arachidonylethanolamine (Anandamide) Head Group Analogues for the Anandamide Transporter}, volume={74}, ISSN={1471-4159}, url={http://dx.doi.org/10.1046/j.1471-4159.2000.0742597.x}, DOI={10.1046/j.1471-4159.2000.0742597.x}, number={6}, journal={Journal of Neurochemistry}, publisher={Wiley}, author={Jarrahian, Abbas and Manna, Sukumar and Edgemond, William S. and Campbell, William B. and Hillard, Cecilia J.}, year={2000}, month=jun, pages={2597–2606} }

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