A Novel Probe for the Cannabinoid Receptor

William A. Devane; Aviva Breuer; Tzviel Sheskin; Torbjörn U.C. Järbe; Moris S. Eisen; Raphael Mechoulam; Torbjörn U.C. Järbe

doi:10.1021/jm00089a018

A Novel Probe for the Cannabinoid Receptor

William A. Devane^*, Aviva Breuer, Tzviel Sheskin, Torbjörn U.C. Järbe, Moris S. Eisen, Raphael Mechoulam, Torbjörn U.C. Järbe

^*Corresponding author for this work

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

162 Scopus citations

Abstract

The 1,1-dimethylheptyl (DMH) homologue of 7-hydroxy-Δ⁶-tetrahydrocannabinol (3) is the most potent cannabimimetic substance reported so far. Hydrogenation of 3 leads to a mixture of the epimers of 5′-(1, 1-dimethylheptyl)-7-hydroxyhexahydrocannabinol or to either the equatorial (7) or to the axial epimer (8), depending on the catalysts and conditions used. Compound 7 discriminates for Δ¹-THC (2) in pigeons (ED₅₀ = 0.002 mg/kg, after 4.5 h), at the potency level of 3, and binds to the cannabinoid receptor with a K_D of 45 pM, considerably lower than the K_i of 180 pM measured for compound 3 and the K_i of 2.0 nM measured for CP-55940 (1), a widely employed ligand. Tritiated 7 was used as a novel probe for the cannabinoid receptor.

Original language	English
Pages (from-to)	2065-2069
Number of pages	5
Journal	Journal of Medicinal Chemistry
Volume	35
Issue number	11
DOIs	https://doi.org/10.1021/jm00089a018
State	Published - 1 May 1992
Externally published	Yes

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title = "A Novel Probe for the Cannabinoid Receptor",

abstract = "The 1,1-dimethylheptyl (DMH) homologue of 7-hydroxy-Δ6-tetrahydrocannabinol (3) is the most potent cannabimimetic substance reported so far. Hydrogenation of 3 leads to a mixture of the epimers of 5′-(1, 1-dimethylheptyl)-7-hydroxyhexahydrocannabinol or to either the equatorial (7) or to the axial epimer (8), depending on the catalysts and conditions used. Compound 7 discriminates for Δ1-THC (2) in pigeons (ED50 = 0.002 mg/kg, after 4.5 h), at the potency level of 3, and binds to the cannabinoid receptor with a KD of 45 pM, considerably lower than the Ki of 180 pM measured for compound 3 and the Ki of 2.0 nM measured for CP-55940 (1), a widely employed ligand. Tritiated 7 was used as a novel probe for the cannabinoid receptor.",

author = "Devane, {William A.} and Aviva Breuer and Tzviel Sheskin and J{\"a}rbe, {Torbj{\"o}rn U.C.} and Eisen, {Moris S.} and Raphael Mechoulam and J{\"a}rbe, {Torbj{\"o}rn U.C.}",

year = "1992",

month = may,

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doi = "10.1021/jm00089a018",

language = "英语",

volume = "35",

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journal = "Journal of Medicinal Chemistry",

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T1 - A Novel Probe for the Cannabinoid Receptor

AU - Devane, William A.

AU - Breuer, Aviva

AU - Sheskin, Tzviel

AU - Järbe, Torbjörn U.C.

AU - Eisen, Moris S.

AU - Mechoulam, Raphael

AU - Järbe, Torbjörn U.C.

PY - 1992/5/1

Y1 - 1992/5/1

N2 - The 1,1-dimethylheptyl (DMH) homologue of 7-hydroxy-Δ6-tetrahydrocannabinol (3) is the most potent cannabimimetic substance reported so far. Hydrogenation of 3 leads to a mixture of the epimers of 5′-(1, 1-dimethylheptyl)-7-hydroxyhexahydrocannabinol or to either the equatorial (7) or to the axial epimer (8), depending on the catalysts and conditions used. Compound 7 discriminates for Δ1-THC (2) in pigeons (ED50 = 0.002 mg/kg, after 4.5 h), at the potency level of 3, and binds to the cannabinoid receptor with a KD of 45 pM, considerably lower than the Ki of 180 pM measured for compound 3 and the Ki of 2.0 nM measured for CP-55940 (1), a widely employed ligand. Tritiated 7 was used as a novel probe for the cannabinoid receptor.

AB - The 1,1-dimethylheptyl (DMH) homologue of 7-hydroxy-Δ6-tetrahydrocannabinol (3) is the most potent cannabimimetic substance reported so far. Hydrogenation of 3 leads to a mixture of the epimers of 5′-(1, 1-dimethylheptyl)-7-hydroxyhexahydrocannabinol or to either the equatorial (7) or to the axial epimer (8), depending on the catalysts and conditions used. Compound 7 discriminates for Δ1-THC (2) in pigeons (ED50 = 0.002 mg/kg, after 4.5 h), at the potency level of 3, and binds to the cannabinoid receptor with a KD of 45 pM, considerably lower than the Ki of 180 pM measured for compound 3 and the Ki of 2.0 nM measured for CP-55940 (1), a widely employed ligand. Tritiated 7 was used as a novel probe for the cannabinoid receptor.

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U2 - 10.1021/jm00089a018

DO - 10.1021/jm00089a018

M3 - 文章

C2 - 1317925

AN - SCOPUS:0026715999

SN - 0022-2623

VL - 35

SP - 2065

EP - 2069

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

IS - 11

ER -

A Novel Probe for the Cannabinoid Receptor

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