Relative efficacies of cannabinoid CB1 receptor agonists in the mouse brain

Thomas H. Burkey; Raymond M. Quock; Paul Consroe; Frederick J. Ehlert; Yoshiaki Hosohata; William R. Roeske; Henry I. Yamamura

doi:10.1016/S0014-2999(97)01255-7

Relative efficacies of cannabinoid CB₁ receptor agonists in the mouse brain

Thomas H. Burkey, Raymond M. Quock, Paul Consroe, Frederick J. Ehlert, Yoshiaki Hosohata, William R. Roeske, Henry I. Yamamura

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

29 Scopus citations

Abstract

We measured (-)-5-(1,1-dimethylheptyl)-2-[5-hydroxy-2-(3-hydroxypropyl)cyclohexyl]-phenol (CP 55,940)-, (-)11-OH-Δ⁸-tetrahydrocannabinol-dimethylheptyl (HU-210)-, anandamide- and Δ⁹-tetrahydrocannabinol-stimulated G protein activation in mouse brain using the [³⁵S]GTPγS functional assay. The K(i) values for these drugs were determined by agonist competition binding with the cannabinoid CB, receptor antagonist [³H] N-(piperidin-1-yl-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H -pyrazole-3-carboxamidehydrochloride ([³H]SR141716A). This information was used to calculate the efficacy for drug stimulation of G protein activity, The rank order of efficacy was CP 55,940 > HU-210 > anandamide > Δ⁹-tetrahydrocannabinol with the latter two drugs being partial agonists. Since efficacy values relate receptor occupancy to functional responses, we believe efficacy values are a better measure of drug-mediated functional responses compared with measurements of drug potency.

Original language	English (US)
Pages (from-to)	295-298
Number of pages	4
Journal	European Journal of Pharmacology
Volume	336
Issue number	2-3
DOIs	https://doi.org/10.1016/S0014-2999(97)01255-7
State	Published - Oct 8 1997

Keywords

Brain
Cannabinoid receptor
Cannnbinoid
Drug efficacy
Mouse
Partial agonist
Tetrahydrocannabinol

ASJC Scopus subject areas

Pharmacology

Access to Document

10.1016/S0014-2999(97)01255-7

Cite this

@article{6e7ddd7d1dee4e62a92b3c7da996f15d,

title = "Relative efficacies of cannabinoid CB1 receptor agonists in the mouse brain",

abstract = "We measured (-)-5-(1,1-dimethylheptyl)-2-[5-hydroxy-2-(3-hydroxypropyl)cyclohexyl]-phenol (CP 55,940)-, (-)11-OH-Δ8-tetrahydrocannabinol-dimethylheptyl (HU-210)-, anandamide- and Δ9-tetrahydrocannabinol-stimulated G protein activation in mouse brain using the [35S]GTPγS functional assay. The K(i) values for these drugs were determined by agonist competition binding with the cannabinoid CB, receptor antagonist [3H] N-(piperidin-1-yl-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H -pyrazole-3-carboxamidehydrochloride ([3H]SR141716A). This information was used to calculate the efficacy for drug stimulation of G protein activity, The rank order of efficacy was CP 55,940 > HU-210 > anandamide > Δ9-tetrahydrocannabinol with the latter two drugs being partial agonists. Since efficacy values relate receptor occupancy to functional responses, we believe efficacy values are a better measure of drug-mediated functional responses compared with measurements of drug potency.",

keywords = "Brain, Cannabinoid receptor, Cannnbinoid, Drug efficacy, Mouse, Partial agonist, Tetrahydrocannabinol",

author = "Burkey, {Thomas H.} and Quock, {Raymond M.} and Paul Consroe and Ehlert, {Frederick J.} and Yoshiaki Hosohata and Roeske, {William R.} and Yamamura, {Henry I.}",

note = "Funding Information: This research was supported in part by grants from the Arizona Disease Control Research Commission and the National Institute on Drug Abuse. ",

year = "1997",

month = oct,

day = "8",

doi = "10.1016/S0014-2999(97)01255-7",

language = "English (US)",

volume = "336",

pages = "295--298",

journal = "European Journal of Pharmacology",

issn = "0014-2999",

publisher = "Elsevier",

number = "2-3",

}

TY - JOUR

T1 - Relative efficacies of cannabinoid CB1 receptor agonists in the mouse brain

AU - Burkey, Thomas H.

AU - Quock, Raymond M.

AU - Consroe, Paul

AU - Ehlert, Frederick J.

AU - Hosohata, Yoshiaki

AU - Roeske, William R.

AU - Yamamura, Henry I.

N1 - Funding Information: This research was supported in part by grants from the Arizona Disease Control Research Commission and the National Institute on Drug Abuse.

PY - 1997/10/8

Y1 - 1997/10/8

N2 - We measured (-)-5-(1,1-dimethylheptyl)-2-[5-hydroxy-2-(3-hydroxypropyl)cyclohexyl]-phenol (CP 55,940)-, (-)11-OH-Δ8-tetrahydrocannabinol-dimethylheptyl (HU-210)-, anandamide- and Δ9-tetrahydrocannabinol-stimulated G protein activation in mouse brain using the [35S]GTPγS functional assay. The K(i) values for these drugs were determined by agonist competition binding with the cannabinoid CB, receptor antagonist [3H] N-(piperidin-1-yl-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H -pyrazole-3-carboxamidehydrochloride ([3H]SR141716A). This information was used to calculate the efficacy for drug stimulation of G protein activity, The rank order of efficacy was CP 55,940 > HU-210 > anandamide > Δ9-tetrahydrocannabinol with the latter two drugs being partial agonists. Since efficacy values relate receptor occupancy to functional responses, we believe efficacy values are a better measure of drug-mediated functional responses compared with measurements of drug potency.

AB - We measured (-)-5-(1,1-dimethylheptyl)-2-[5-hydroxy-2-(3-hydroxypropyl)cyclohexyl]-phenol (CP 55,940)-, (-)11-OH-Δ8-tetrahydrocannabinol-dimethylheptyl (HU-210)-, anandamide- and Δ9-tetrahydrocannabinol-stimulated G protein activation in mouse brain using the [35S]GTPγS functional assay. The K(i) values for these drugs were determined by agonist competition binding with the cannabinoid CB, receptor antagonist [3H] N-(piperidin-1-yl-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H -pyrazole-3-carboxamidehydrochloride ([3H]SR141716A). This information was used to calculate the efficacy for drug stimulation of G protein activity, The rank order of efficacy was CP 55,940 > HU-210 > anandamide > Δ9-tetrahydrocannabinol with the latter two drugs being partial agonists. Since efficacy values relate receptor occupancy to functional responses, we believe efficacy values are a better measure of drug-mediated functional responses compared with measurements of drug potency.

KW - Brain

KW - Cannabinoid receptor

KW - Cannnbinoid

KW - Drug efficacy

KW - Mouse

KW - Partial agonist

KW - Tetrahydrocannabinol

UR - http://www.scopus.com/inward/record.url?scp=0030720938&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030720938&partnerID=8YFLogxK

U2 - 10.1016/S0014-2999(97)01255-7

DO - 10.1016/S0014-2999(97)01255-7

M3 - Article

C2 - 9384246

AN - SCOPUS:0030720938

SN - 0014-2999

VL - 336

SP - 295

EP - 298

JO - European Journal of Pharmacology

JF - European Journal of Pharmacology

IS - 2-3

ER -