SR141716A is an inverse agonist at the human cannabinoid CB1 receptor

Robert S. Landsman; Thomas H. Burkey; Paul Consroe; William R. Roeske; Henry I. Yamamura

doi:10.1016/S0014-2999(97)01160-6

SR141716A is an inverse agonist at the human cannabinoid CB₁ receptor

Robert S. Landsman, Thomas H. Burkey, Paul Consroe, William R. Roeske, Henry I. Yamamura

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

243 Scopus citations

Abstract

The effects of R(+)-[2,3-dihydro-5-methyl-3-[(morpholinyl) methyl]pyrrolo[1,2,3-de]-1,4-benzoxazin-yl]-(1-napthalenyl)methanone mesylate (WIN 55,212-2) and N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-3-pyrazole -carboxamide (SR141716A) on guanosine-5'-O-(3-[³⁵S]thio)triphosphate ([³⁵S]GTPγS) binding to membranes isolated from human cannabinoid CB₁ receptor-transfected Chinese hamster ovary (CHO) cells were examined. WIN 55,212-2 stimulated [³⁵S]GTPγS binding 76.3% above basal levels whereas SR141716A produced a 22.3% decrease in basal [³⁵S]GTPγS binding. These findings demonstrate that WIN 55,212-2 is an agonist and SR141716A is an inverse agonist in this system.

Original language	English (US)
Pages (from-to)	R1-R2
Journal	European Journal of Pharmacology
Volume	334
Issue number	1
DOIs	https://doi.org/10.1016/S0014-2999(97)01160-6
State	Published - Sep 3 1997

Keywords

Cannobinoid receptor human
Inverse agonist
SR141716A

ASJC Scopus subject areas

Pharmacology

Access to Document

10.1016/S0014-2999(97)01160-6

Cite this

@article{269be822236b47349fb042cba6c7567c,

title = "SR141716A is an inverse agonist at the human cannabinoid CB1 receptor",

abstract = "The effects of R(+)-[2,3-dihydro-5-methyl-3-[(morpholinyl) methyl]pyrrolo[1,2,3-de]-1,4-benzoxazin-yl]-(1-napthalenyl)methanone mesylate (WIN 55,212-2) and N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-3-pyrazole -carboxamide (SR141716A) on guanosine-5'-O-(3-[35S]thio)triphosphate ([35S]GTPγS) binding to membranes isolated from human cannabinoid CB1 receptor-transfected Chinese hamster ovary (CHO) cells were examined. WIN 55,212-2 stimulated [35S]GTPγS binding 76.3% above basal levels whereas SR141716A produced a 22.3% decrease in basal [35S]GTPγS binding. These findings demonstrate that WIN 55,212-2 is an agonist and SR141716A is an inverse agonist in this system.",

keywords = "Cannobinoid receptor human, Inverse agonist, SR141716A",

author = "Landsman, {Robert S.} and Burkey, {Thomas H.} and Paul Consroe and Roeske, {William R.} and Yamamura, {Henry I.}",

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

year = "1997",

month = sep,

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AU - Landsman, Robert S.

AU - Burkey, Thomas H.

AU - Consroe, Paul

AU - Roeske, William R.

AU - Yamamura, Henry I.

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

PY - 1997/9/3

Y1 - 1997/9/3

N2 - The effects of R(+)-[2,3-dihydro-5-methyl-3-[(morpholinyl) methyl]pyrrolo[1,2,3-de]-1,4-benzoxazin-yl]-(1-napthalenyl)methanone mesylate (WIN 55,212-2) and N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-3-pyrazole -carboxamide (SR141716A) on guanosine-5'-O-(3-[35S]thio)triphosphate ([35S]GTPγS) binding to membranes isolated from human cannabinoid CB1 receptor-transfected Chinese hamster ovary (CHO) cells were examined. WIN 55,212-2 stimulated [35S]GTPγS binding 76.3% above basal levels whereas SR141716A produced a 22.3% decrease in basal [35S]GTPγS binding. These findings demonstrate that WIN 55,212-2 is an agonist and SR141716A is an inverse agonist in this system.

AB - The effects of R(+)-[2,3-dihydro-5-methyl-3-[(morpholinyl) methyl]pyrrolo[1,2,3-de]-1,4-benzoxazin-yl]-(1-napthalenyl)methanone mesylate (WIN 55,212-2) and N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-3-pyrazole -carboxamide (SR141716A) on guanosine-5'-O-(3-[35S]thio)triphosphate ([35S]GTPγS) binding to membranes isolated from human cannabinoid CB1 receptor-transfected Chinese hamster ovary (CHO) cells were examined. WIN 55,212-2 stimulated [35S]GTPγS binding 76.3% above basal levels whereas SR141716A produced a 22.3% decrease in basal [35S]GTPγS binding. These findings demonstrate that WIN 55,212-2 is an agonist and SR141716A is an inverse agonist in this system.

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KW - Inverse agonist

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