[125]I-Spectramide: A novel benzamide displaying potent and selective effects at the D2 dopamine receptor

Patricia M. Sánchez-Roa; Dimitri E. Grigoriadis; Alan A. Wilson; John Sharkey; Robert F. Dannals; Victor L. Villemagne; Dean F. Wong; Henry N. Wagner; Michael J. Kuhar

doi:10.1016/0024-3205(89)90523-7

^[125]I-Spectramide: A novel benzamide displaying potent and selective effects at the D₂ dopamine receptor

Patricia M. Sánchez-Roa, Dimitri E. Grigoriadis, Alan A. Wilson, John Sharkey, Robert F. Dannals, Victor L. Villemagne, Dean F. Wong, Henry N. Wagner, Michael J. Kuhar

School of Medicine

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

10 Scopus citations

Abstract

The new substituted benzamide Spectramide, (N-[2-[4-iodobenzyl-N-methylamino]-2-methoxy-4-ethyl]-5-chloro-methylamine] benzamide) labelled with ¹²⁵I was used as a potent and highly selective dopamine-D₂ receptor antagonist in rat striatal homogenates for in vitro receptor binding. Kinetic experiments demonstrated the reversibility of the binding and the estimated Kd from saturation analysis was 25 pM, with a Bmax of 20 pmol/g of tissue. Competition studies showed that spectramide did not interact potently with the D₁ or dopamine-uptake site. Drugs known to interact with other receptor systems were weak competitors of the binding, while binding was potently inhibited by other D₂ antagonists, such as spiperone and eticlopride. These data indicate that Spectramide binds selectively and with high affinity to the dopamine D₂ receptors, and may prove to be a useful tool for the study of these receptors in vivo using PET or SPECT.

Original language	English (US)
Pages (from-to)	1821-1829
Number of pages	9
Journal	Life Sciences
Volume	45
Issue number	19
DOIs	https://doi.org/10.1016/0024-3205(89)90523-7
State	Published - 1989

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology
Pharmacology, Toxicology and Pharmaceutics(all)

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10.1016/0024-3205(89)90523-7

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@article{8eed337155f44127b24a993ab7893142,

title = "[125]I-Spectramide: A novel benzamide displaying potent and selective effects at the D2 dopamine receptor",

abstract = "The new substituted benzamide Spectramide, (N-[2-[4-iodobenzyl-N-methylamino]-2-methoxy-4-ethyl]-5-chloro-methylamine] benzamide) labelled with 125I was used as a potent and highly selective dopamine-D2 receptor antagonist in rat striatal homogenates for in vitro receptor binding. Kinetic experiments demonstrated the reversibility of the binding and the estimated Kd from saturation analysis was 25 pM, with a Bmax of 20 pmol/g of tissue. Competition studies showed that spectramide did not interact potently with the D1 or dopamine-uptake site. Drugs known to interact with other receptor systems were weak competitors of the binding, while binding was potently inhibited by other D2 antagonists, such as spiperone and eticlopride. These data indicate that Spectramide binds selectively and with high affinity to the dopamine D2 receptors, and may prove to be a useful tool for the study of these receptors in vivo using PET or SPECT.",

author = "S{\'a}nchez-Roa, {Patricia M.} and Grigoriadis, {Dimitri E.} and Wilson, {Alan A.} and John Sharkey and Dannals, {Robert F.} and Villemagne, {Victor L.} and Wong, {Dean F.} and Wagner, {Henry N.} and Kuhar, {Michael J.}",

note = "Funding Information: Special thanks to Michele Milberger for her technical assistance and Terry Pierce for secretarial assistance. D.E.G. is a Medical Research Council of Canada post-doctoral fellow. This work was supported in part by USPHS grants NS-15080 and CA-32845 and by the NIDA Addiction Research Center.",

year = "1989",

doi = "10.1016/0024-3205(89)90523-7",

language = "English (US)",

volume = "45",

pages = "1821--1829",

journal = "Life Sciences",

issn = "0024-3205",

publisher = "Elsevier Inc.",

number = "19",

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TY - JOUR

T1 - [125]I-Spectramide

T2 - A novel benzamide displaying potent and selective effects at the D2 dopamine receptor

AU - Sánchez-Roa, Patricia M.

AU - Grigoriadis, Dimitri E.

AU - Wilson, Alan A.

AU - Sharkey, John

AU - Dannals, Robert F.

AU - Villemagne, Victor L.

AU - Wong, Dean F.

AU - Wagner, Henry N.

AU - Kuhar, Michael J.

N1 - Funding Information: Special thanks to Michele Milberger for her technical assistance and Terry Pierce for secretarial assistance. D.E.G. is a Medical Research Council of Canada post-doctoral fellow. This work was supported in part by USPHS grants NS-15080 and CA-32845 and by the NIDA Addiction Research Center.

PY - 1989

Y1 - 1989

N2 - The new substituted benzamide Spectramide, (N-[2-[4-iodobenzyl-N-methylamino]-2-methoxy-4-ethyl]-5-chloro-methylamine] benzamide) labelled with 125I was used as a potent and highly selective dopamine-D2 receptor antagonist in rat striatal homogenates for in vitro receptor binding. Kinetic experiments demonstrated the reversibility of the binding and the estimated Kd from saturation analysis was 25 pM, with a Bmax of 20 pmol/g of tissue. Competition studies showed that spectramide did not interact potently with the D1 or dopamine-uptake site. Drugs known to interact with other receptor systems were weak competitors of the binding, while binding was potently inhibited by other D2 antagonists, such as spiperone and eticlopride. These data indicate that Spectramide binds selectively and with high affinity to the dopamine D2 receptors, and may prove to be a useful tool for the study of these receptors in vivo using PET or SPECT.

AB - The new substituted benzamide Spectramide, (N-[2-[4-iodobenzyl-N-methylamino]-2-methoxy-4-ethyl]-5-chloro-methylamine] benzamide) labelled with 125I was used as a potent and highly selective dopamine-D2 receptor antagonist in rat striatal homogenates for in vitro receptor binding. Kinetic experiments demonstrated the reversibility of the binding and the estimated Kd from saturation analysis was 25 pM, with a Bmax of 20 pmol/g of tissue. Competition studies showed that spectramide did not interact potently with the D1 or dopamine-uptake site. Drugs known to interact with other receptor systems were weak competitors of the binding, while binding was potently inhibited by other D2 antagonists, such as spiperone and eticlopride. These data indicate that Spectramide binds selectively and with high affinity to the dopamine D2 receptors, and may prove to be a useful tool for the study of these receptors in vivo using PET or SPECT.

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JO - Life Sciences

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ER -

^[125]I-Spectramide: A novel benzamide displaying potent and selective effects at the D₂ dopamine receptor

Abstract

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