Cannabinol derivatives: Binding to cannabinoid receptors and inhibition of adenylylcyclase

Man Hee Rhee; Zvi Vogel; Jacob Barg; Michael Bayewitch; Rivka Levy; Lumir Hanuš; Aviva Breuer; Raphael Mechoulam

doi:10.1021/jm970126f

Cannabinol derivatives: Binding to cannabinoid receptors and inhibition of adenylylcyclase

Man Hee Rhee, Zvi Vogel, Jacob Barg, Michael Bayewitch, Rivka Levy, Lumir Hanuš, Aviva Breuer, Raphael Mechoulam^*

^*Corresponding author for this work

School of Pharmacy

Research output: Contribution to journal › Article › peer-review

172 Scopus citations

Abstract

Several derivatives of cannabinol and the 1,1-dimethylheptyl homolog (DMH) of cannabinol were prepared and assayed for binding to the brain and the peripheral cannabinoid receptors (CB₁ and CB₂), as well as for activation of CB₁- and CB₂-mediated inhibition of adenylylcyclase. The DMH derivatives were much more potent than the pentyl (i.e., cannabinol) derivatives. 11-Hydroxycannabinol (4a) was found to bind potently to both CB₁ and CB₂ (K(i) values of 38.0 ± 7.2 and 26.6 ± 5.5 nM, respectively) and to inhibit CB₁-mediated adenylylcyclase with an EC₅₀ of 58.1 ± 6.2 nM but to cause only 20% inhibition of CB₂-mediated adenylylcyclase at 10 μM. It behaves as a specific, though not potent, CB₂ antagonist. 11- Hydroxycannabinol-DMH (4b) is a very potent agonist for both CB₁ and CB₂ (K(i) values of 100 ± 50 and 200 ± 40 pM; EC₅₀ of adenylylcyclase inhibition 56.2 ± 4.2 and 207.5 ± 27.8 pM, respectively).

Original language	English
Pages (from-to)	3228-3233
Number of pages	6
Journal	Journal of Medicinal Chemistry
Volume	40
Issue number	20
DOIs	https://doi.org/10.1021/jm970126f
State	Published - 1997

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title = "Cannabinol derivatives: Binding to cannabinoid receptors and inhibition of adenylylcyclase",

abstract = "Several derivatives of cannabinol and the 1,1-dimethylheptyl homolog (DMH) of cannabinol were prepared and assayed for binding to the brain and the peripheral cannabinoid receptors (CB1 and CB2), as well as for activation of CB1- and CB2-mediated inhibition of adenylylcyclase. The DMH derivatives were much more potent than the pentyl (i.e., cannabinol) derivatives. 11-Hydroxycannabinol (4a) was found to bind potently to both CB1 and CB2 (K(i) values of 38.0 ± 7.2 and 26.6 ± 5.5 nM, respectively) and to inhibit CB1-mediated adenylylcyclase with an EC50 of 58.1 ± 6.2 nM but to cause only 20% inhibition of CB2-mediated adenylylcyclase at 10 μM. It behaves as a specific, though not potent, CB2 antagonist. 11- Hydroxycannabinol-DMH (4b) is a very potent agonist for both CB1 and CB2 (K(i) values of 100 ± 50 and 200 ± 40 pM; EC50 of adenylylcyclase inhibition 56.2 ± 4.2 and 207.5 ± 27.8 pM, respectively).",

author = "Rhee, {Man Hee} and Zvi Vogel and Jacob Barg and Michael Bayewitch and Rivka Levy and Lumir Hanu{\v s} and Aviva Breuer and Raphael Mechoulam",

year = "1997",

doi = "10.1021/jm970126f",

language = "אנגלית",

volume = "40",

pages = "3228--3233",

journal = "Journal of Medicinal Chemistry",

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publisher = "American Chemical Society",

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T1 - Cannabinol derivatives

T2 - Binding to cannabinoid receptors and inhibition of adenylylcyclase

AU - Rhee, Man Hee

AU - Vogel, Zvi

AU - Barg, Jacob

AU - Bayewitch, Michael

AU - Levy, Rivka

AU - Hanuš, Lumir

AU - Breuer, Aviva

AU - Mechoulam, Raphael

PY - 1997

Y1 - 1997

N2 - Several derivatives of cannabinol and the 1,1-dimethylheptyl homolog (DMH) of cannabinol were prepared and assayed for binding to the brain and the peripheral cannabinoid receptors (CB1 and CB2), as well as for activation of CB1- and CB2-mediated inhibition of adenylylcyclase. The DMH derivatives were much more potent than the pentyl (i.e., cannabinol) derivatives. 11-Hydroxycannabinol (4a) was found to bind potently to both CB1 and CB2 (K(i) values of 38.0 ± 7.2 and 26.6 ± 5.5 nM, respectively) and to inhibit CB1-mediated adenylylcyclase with an EC50 of 58.1 ± 6.2 nM but to cause only 20% inhibition of CB2-mediated adenylylcyclase at 10 μM. It behaves as a specific, though not potent, CB2 antagonist. 11- Hydroxycannabinol-DMH (4b) is a very potent agonist for both CB1 and CB2 (K(i) values of 100 ± 50 and 200 ± 40 pM; EC50 of adenylylcyclase inhibition 56.2 ± 4.2 and 207.5 ± 27.8 pM, respectively).

AB - Several derivatives of cannabinol and the 1,1-dimethylheptyl homolog (DMH) of cannabinol were prepared and assayed for binding to the brain and the peripheral cannabinoid receptors (CB1 and CB2), as well as for activation of CB1- and CB2-mediated inhibition of adenylylcyclase. The DMH derivatives were much more potent than the pentyl (i.e., cannabinol) derivatives. 11-Hydroxycannabinol (4a) was found to bind potently to both CB1 and CB2 (K(i) values of 38.0 ± 7.2 and 26.6 ± 5.5 nM, respectively) and to inhibit CB1-mediated adenylylcyclase with an EC50 of 58.1 ± 6.2 nM but to cause only 20% inhibition of CB2-mediated adenylylcyclase at 10 μM. It behaves as a specific, though not potent, CB2 antagonist. 11- Hydroxycannabinol-DMH (4b) is a very potent agonist for both CB1 and CB2 (K(i) values of 100 ± 50 and 200 ± 40 pM; EC50 of adenylylcyclase inhibition 56.2 ± 4.2 and 207.5 ± 27.8 pM, respectively).

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Cannabinol derivatives: Binding to cannabinoid receptors and inhibition of adenylylcyclase

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