Fluoro-norchloroepibatidine: Preclinical assessment of acute toxicity

Patricia E. Molina; Yu Shin Ding; F. Ivy Carroll; F. Liang; Nora D. Volkow; Naomi Pappas; Michael Kuhar; Naji Abumrad; S. John Gatley; Joanna S. Fowler

doi:10.1016/S0969-8051(97)00120-0

Fluoro-norchloroepibatidine: Preclinical assessment of acute toxicity

Patricia E. Molina, Yu Shin Ding, F. Ivy Carroll, F. Liang, Nora D. Volkow, Naomi Pappas, Michael Kuhar, Naji Abumrad, S. John Gatley, Joanna S. Fowler

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

69 Scopus citations

Abstract

¹⁸Fluoro-norchloroepibatidine (exo-2-(6-fluoro-3-pyridyl)-7- azabicyclo-[2.2.1]heptane [NFEP]), a labeled derivative of epibatidine, has shown promise for imaging brain nicotinic acetylcholine receptors with PET. We determined the dose-dependent effects of NFEP in conscious rats. NFEP (1.5 μg/kg; administered intravenously) resulted in 30% mortality. Neither 0.5 μg/kg or 0.25 μg/kg NFEP resulted in any significant changes in cardiorespiratory parameters, but plasma catecholamines increased (2- to 3- fold). Further studies are needed to determine the safety of NFEP that are specifically designed to assess the catecholamine response. Our results suggest that it is not advisable to initiate human PET studies with [¹⁸F]- NFEP without further evidence supporting its safety.

Original language	English
Pages (from-to)	743-747
Number of pages	5
Journal	Nuclear Medicine and Biology
Volume	24
Issue number	8
DOIs	https://doi.org/10.1016/S0969-8051(97)00120-0
State	Published - Nov 1997
Externally published	Yes

Keywords

Fluoro-norchloroepibatidine
Hemodynamics
Nicotinic acetylcholine receptors
Positron emission tomography
Toxicity

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10.1016/S0969-8051(97)00120-0

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@article{0662b81ffa454f5d926005a665b84dd3,

title = "Fluoro-norchloroepibatidine: Preclinical assessment of acute toxicity",

abstract = "18Fluoro-norchloroepibatidine (exo-2-(6-fluoro-3-pyridyl)-7- azabicyclo-[2.2.1]heptane [NFEP]), a labeled derivative of epibatidine, has shown promise for imaging brain nicotinic acetylcholine receptors with PET. We determined the dose-dependent effects of NFEP in conscious rats. NFEP (1.5 μg/kg; administered intravenously) resulted in 30% mortality. Neither 0.5 μg/kg or 0.25 μg/kg NFEP resulted in any significant changes in cardiorespiratory parameters, but plasma catecholamines increased (2- to 3- fold). Further studies are needed to determine the safety of NFEP that are specifically designed to assess the catecholamine response. Our results suggest that it is not advisable to initiate human PET studies with [18F]- NFEP without further evidence supporting its safety.",

keywords = "Fluoro-norchloroepibatidine, Hemodynamics, Nicotinic acetylcholine receptors, Positron emission tomography, Toxicity",

author = "Molina, {Patricia E.} and Ding, {Yu Shin} and Carroll, {F. Ivy} and F. Liang and Volkow, {Nora D.} and Naomi Pappas and Michael Kuhar and Naji Abumrad and Gatley, {S. John} and Fowler, {Joanna S.}",

note = "Funding Information: This research eras carried out, in part, at Brookhaven National Laboratory under contract DE-AC02-76CH00016 with the U.S. Department of Energy and supported by its Office of Health and Environmental Research. This research was also supported in part by the Office of Naval Research (N00014-95-l-0865), by the National Institutes of Health (NINDS NS-153800, and RR-00165), by the Council for Tobacco Research, by the National Institutes on Drug Abuse and by Fisons Pharmaceuticals (now AstraArcus USA). The authors are grateful to Payton King, Rebecca Naukam and Luping Qian for their excellent technical assistance.",

year = "1997",

month = nov,

doi = "10.1016/S0969-8051(97)00120-0",

language = "English",

volume = "24",

pages = "743--747",

journal = "Nuclear Medicine and Biology",

issn = "0969-8051",

publisher = "Elsevier Inc.",

number = "8",

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TY - JOUR

T1 - Fluoro-norchloroepibatidine

T2 - Preclinical assessment of acute toxicity

AU - Molina, Patricia E.

AU - Ding, Yu Shin

AU - Carroll, F. Ivy

AU - Liang, F.

AU - Volkow, Nora D.

AU - Pappas, Naomi

AU - Kuhar, Michael

AU - Abumrad, Naji

AU - Gatley, S. John

AU - Fowler, Joanna S.

N1 - Funding Information: This research eras carried out, in part, at Brookhaven National Laboratory under contract DE-AC02-76CH00016 with the U.S. Department of Energy and supported by its Office of Health and Environmental Research. This research was also supported in part by the Office of Naval Research (N00014-95-l-0865), by the National Institutes of Health (NINDS NS-153800, and RR-00165), by the Council for Tobacco Research, by the National Institutes on Drug Abuse and by Fisons Pharmaceuticals (now AstraArcus USA). The authors are grateful to Payton King, Rebecca Naukam and Luping Qian for their excellent technical assistance.

PY - 1997/11

Y1 - 1997/11

N2 - 18Fluoro-norchloroepibatidine (exo-2-(6-fluoro-3-pyridyl)-7- azabicyclo-[2.2.1]heptane [NFEP]), a labeled derivative of epibatidine, has shown promise for imaging brain nicotinic acetylcholine receptors with PET. We determined the dose-dependent effects of NFEP in conscious rats. NFEP (1.5 μg/kg; administered intravenously) resulted in 30% mortality. Neither 0.5 μg/kg or 0.25 μg/kg NFEP resulted in any significant changes in cardiorespiratory parameters, but plasma catecholamines increased (2- to 3- fold). Further studies are needed to determine the safety of NFEP that are specifically designed to assess the catecholamine response. Our results suggest that it is not advisable to initiate human PET studies with [18F]- NFEP without further evidence supporting its safety.

AB - 18Fluoro-norchloroepibatidine (exo-2-(6-fluoro-3-pyridyl)-7- azabicyclo-[2.2.1]heptane [NFEP]), a labeled derivative of epibatidine, has shown promise for imaging brain nicotinic acetylcholine receptors with PET. We determined the dose-dependent effects of NFEP in conscious rats. NFEP (1.5 μg/kg; administered intravenously) resulted in 30% mortality. Neither 0.5 μg/kg or 0.25 μg/kg NFEP resulted in any significant changes in cardiorespiratory parameters, but plasma catecholamines increased (2- to 3- fold). Further studies are needed to determine the safety of NFEP that are specifically designed to assess the catecholamine response. Our results suggest that it is not advisable to initiate human PET studies with [18F]- NFEP without further evidence supporting its safety.

KW - Fluoro-norchloroepibatidine

KW - Hemodynamics

KW - Nicotinic acetylcholine receptors

KW - Positron emission tomography

KW - Toxicity

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JO - Nuclear Medicine and Biology

JF - Nuclear Medicine and Biology

IS - 8

ER -

Fluoro-norchloroepibatidine: Preclinical assessment of acute toxicity

Abstract

Keywords

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