Lobelane analogues as novel ligands for the vesicular monoamine transporter-2

Guangrong Zheng; Linda P. Dwoskin; Agripina G. Deaciuc; Jun Zhu; Marlon D. Jones; Peter A. Crooks

doi:10.1016/j.bmc.2005.04.013

Lobelane analogues as novel ligands for the vesicular monoamine transporter-2

Guangrong Zheng, Linda P. Dwoskin, Agripina G. Deaciuc, Jun Zhu, Marlon D. Jones, Peter A. Crooks

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

36 Scopus citations

Abstract

A series of lobelane analogues has been synthesized and their structure-activity relationships at the vesicular monoamine transporter-2 (VMAT2) have been evaluated. The most potent analogues in this series were the cis-2,6-piperidino analogues, 25b, 27b, 28b, and 30b, with K_i values ranging from 430 to 580 nM.

Original language	English
Pages (from-to)	3899-3909
Number of pages	11
Journal	Bioorganic and Medicinal Chemistry
Volume	13
Issue number	12
DOIs	https://doi.org/10.1016/j.bmc.2005.04.013
State	Published - Jun 2 2005

Bibliographical note

Funding Information:
This research was supported by NIH grants DA 00399 and DA 13519. The authors also gratefully acknowledge the generous gift of [ 3 H]DTBZ from Dr. Michael R. Kilbourn (supported by NIH Grant MH 47611). The authors also thank Mr. Robert King of the Environmental Research and Training Laboratory, University of Kentucky for performing the elemental analyses. For purposes of full disclosure, the University of Kentucky holds patents on lobeline and lobeline analogues, which have been licensed by Yaupon Therapeutics Inc. (Lexington, KY). A potential royalty stream to G.Z., L.P.D., M.D.J., and P.A.C. may occur consistent with University of Kentucky policy. Both L.P.D. and P.A.C. are founders of, and have financial interest in Yaupon Therapeutics Inc.

Funding

This research was supported by NIH grants DA 00399 and DA 13519. The authors also gratefully acknowledge the generous gift of [ 3 H]DTBZ from Dr. Michael R. Kilbourn (supported by NIH Grant MH 47611). The authors also thank Mr. Robert King of the Environmental Research and Training Laboratory, University of Kentucky for performing the elemental analyses. For purposes of full disclosure, the University of Kentucky holds patents on lobeline and lobeline analogues, which have been licensed by Yaupon Therapeutics Inc. (Lexington, KY). A potential royalty stream to G.Z., L.P.D., M.D.J., and P.A.C. may occur consistent with University of Kentucky policy. Both L.P.D. and P.A.C. are founders of, and have financial interest in Yaupon Therapeutics Inc.

Funders	Funder number
National Institutes of Health (NIH)	MH 47611, DA 00399
National Institute on Drug Abuse	R01DA013519

Keywords

Lobeline
Methamphetamine
Structure-activity relationships
Vesicular monoamine transporter

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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10.1016/j.bmc.2005.04.013

Cite this

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title = "Lobelane analogues as novel ligands for the vesicular monoamine transporter-2",

abstract = "A series of lobelane analogues has been synthesized and their structure-activity relationships at the vesicular monoamine transporter-2 (VMAT2) have been evaluated. The most potent analogues in this series were the cis-2,6-piperidino analogues, 25b, 27b, 28b, and 30b, with Ki values ranging from 430 to 580 nM.",

keywords = "Lobeline, Methamphetamine, Structure-activity relationships, Vesicular monoamine transporter",

author = "Guangrong Zheng and Dwoskin, {Linda P.} and Deaciuc, {Agripina G.} and Jun Zhu and Jones, {Marlon D.} and Crooks, {Peter A.}",

note = "Funding Information: This research was supported by NIH grants DA 00399 and DA 13519. The authors also gratefully acknowledge the generous gift of [ 3 H]DTBZ from Dr. Michael R. Kilbourn (supported by NIH Grant MH 47611). The authors also thank Mr. Robert King of the Environmental Research and Training Laboratory, University of Kentucky for performing the elemental analyses. For purposes of full disclosure, the University of Kentucky holds patents on lobeline and lobeline analogues, which have been licensed by Yaupon Therapeutics Inc. (Lexington, KY). A potential royalty stream to G.Z., L.P.D., M.D.J., and P.A.C. may occur consistent with University of Kentucky policy. Both L.P.D. and P.A.C. are founders of, and have financial interest in Yaupon Therapeutics Inc. ",

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doi = "10.1016/j.bmc.2005.04.013",

language = "English",

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AU - Zheng, Guangrong

AU - Dwoskin, Linda P.

AU - Deaciuc, Agripina G.

AU - Zhu, Jun

AU - Jones, Marlon D.

AU - Crooks, Peter A.

N1 - Funding Information: This research was supported by NIH grants DA 00399 and DA 13519. The authors also gratefully acknowledge the generous gift of [ 3 H]DTBZ from Dr. Michael R. Kilbourn (supported by NIH Grant MH 47611). The authors also thank Mr. Robert King of the Environmental Research and Training Laboratory, University of Kentucky for performing the elemental analyses. For purposes of full disclosure, the University of Kentucky holds patents on lobeline and lobeline analogues, which have been licensed by Yaupon Therapeutics Inc. (Lexington, KY). A potential royalty stream to G.Z., L.P.D., M.D.J., and P.A.C. may occur consistent with University of Kentucky policy. Both L.P.D. and P.A.C. are founders of, and have financial interest in Yaupon Therapeutics Inc.

PY - 2005/6/2

Y1 - 2005/6/2

N2 - A series of lobelane analogues has been synthesized and their structure-activity relationships at the vesicular monoamine transporter-2 (VMAT2) have been evaluated. The most potent analogues in this series were the cis-2,6-piperidino analogues, 25b, 27b, 28b, and 30b, with Ki values ranging from 430 to 580 nM.

AB - A series of lobelane analogues has been synthesized and their structure-activity relationships at the vesicular monoamine transporter-2 (VMAT2) have been evaluated. The most potent analogues in this series were the cis-2,6-piperidino analogues, 25b, 27b, 28b, and 30b, with Ki values ranging from 430 to 580 nM.

KW - Lobeline

KW - Methamphetamine

KW - Structure-activity relationships

KW - Vesicular monoamine transporter

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Lobelane analogues as novel ligands for the vesicular monoamine transporter-2

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

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