PET neuroimaging with [11C]venlafaxine: Serotonin uptake inhibition, biodistribution and binding in living pig brain

D. F. Smith; P. N. Jensen; A. D. Gee; S. B. Hansen; E. Danielsen; F. Andersen; P. A. Saiz; A. Gjedde

doi:10.1016/S0924-977X(97)00403-3

PET neuroimaging with [¹¹C]venlafaxine: Serotonin uptake inhibition, biodistribution and binding in living pig brain

D. F. Smith, P. N. Jensen, A. D. Gee, S. B. Hansen, E. Danielsen, F. Andersen, P. A. Saiz, A. Gjedde

School of Medicine

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

31 Scopus citations

Abstract

The brain binding kinetics and distribution of the antidepressant venlafaxine, labelled with ¹¹C in the O-methyl position, was studied by PET after intravenous injection in anesthetized pigs. In addition, venlafaxine's action on serotonin (5-HT) uptake was studied in vitro in blood platelets obtain from humans or pigs. Venlafaxine resembled imipramine, paroxetine and citalopram in causing a dose-dependent inhibition of 5-HT uptake in blood platelets from pigs and humans. Venlafaxine-derived radioactivity entered the living brain readily and showed higher binding potentials in diencephalic and telencephalic regions than in cerebellum. Acute administration of an antidepressant drug (i.e. imipramine, citalopram or paroxetine) enhanced the distribution and altered the binding of venlafaxine in certain brain regions. The findings show that [¹¹C]venlafaxine is not an ideal PET radiotracer mainly because of its relatively low binding potentials and its lack of specificity for the 5-HT transporter in living brain.

Original language	English (US)
Pages (from-to)	195-200
Number of pages	6
Journal	European Neuropsychopharmacology
Volume	7
Issue number	3
DOIs	https://doi.org/10.1016/S0924-977X(97)00403-3
State	Published - Aug 1 1997

Keywords

Antidepressant binding
Blood platelet
Citalopram
Imipramine
Paroxetine
Pig brain
Serotonin reuptake
Venlafaxine

ASJC Scopus subject areas

Pharmacology
Neurology
Clinical Neurology
Psychiatry and Mental health
Biological Psychiatry
Pharmacology (medical)

Access to Document

10.1016/S0924-977X(97)00403-3

Cite this

@article{be282d07214a469995135acd361ce3a1,

title = "PET neuroimaging with [11C]venlafaxine: Serotonin uptake inhibition, biodistribution and binding in living pig brain",

abstract = "The brain binding kinetics and distribution of the antidepressant venlafaxine, labelled with 11C in the O-methyl position, was studied by PET after intravenous injection in anesthetized pigs. In addition, venlafaxine's action on serotonin (5-HT) uptake was studied in vitro in blood platelets obtain from humans or pigs. Venlafaxine resembled imipramine, paroxetine and citalopram in causing a dose-dependent inhibition of 5-HT uptake in blood platelets from pigs and humans. Venlafaxine-derived radioactivity entered the living brain readily and showed higher binding potentials in diencephalic and telencephalic regions than in cerebellum. Acute administration of an antidepressant drug (i.e. imipramine, citalopram or paroxetine) enhanced the distribution and altered the binding of venlafaxine in certain brain regions. The findings show that [11C]venlafaxine is not an ideal PET radiotracer mainly because of its relatively low binding potentials and its lack of specificity for the 5-HT transporter in living brain.",

keywords = "Antidepressant binding, Blood platelet, Citalopram, Imipramine, Paroxetine, Pig brain, Serotonin reuptake, Venlafaxine",

author = "Smith, {D. F.} and Jensen, {P. N.} and Gee, {A. D.} and Hansen, {S. B.} and E. Danielsen and F. Andersen and Saiz, {P. A.} and A. Gjedde",

note = "Funding Information: We thank Bente, Helle, Niels and Torben at the PET Center of Aarhus University Hospitals, Elin, Bodil and Pia at the Psychiatric Hospital of Aarhus University and Walther, Per and Diane of the animal colony for their skillful assistance, Sharon Burns of Wyeth (Princeton, N.J.) for samples of venlafaxine and O-desmethyl-venlafaxine, Eric Muth of Wyeth for information concerning pharmacological properties of venlafaxine, and H{\o}rslev's fund for financial support.",

year = "1997",

month = aug,

day = "1",

doi = "10.1016/S0924-977X(97)00403-3",

language = "English (US)",

volume = "7",

pages = "195--200",

journal = "European Neuropsychopharmacology",

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publisher = "Elsevier",

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TY - JOUR

T1 - PET neuroimaging with [11C]venlafaxine

T2 - Serotonin uptake inhibition, biodistribution and binding in living pig brain

AU - Smith, D. F.

AU - Jensen, P. N.

AU - Gee, A. D.

AU - Hansen, S. B.

AU - Danielsen, E.

AU - Andersen, F.

AU - Saiz, P. A.

AU - Gjedde, A.

N1 - Funding Information: We thank Bente, Helle, Niels and Torben at the PET Center of Aarhus University Hospitals, Elin, Bodil and Pia at the Psychiatric Hospital of Aarhus University and Walther, Per and Diane of the animal colony for their skillful assistance, Sharon Burns of Wyeth (Princeton, N.J.) for samples of venlafaxine and O-desmethyl-venlafaxine, Eric Muth of Wyeth for information concerning pharmacological properties of venlafaxine, and Hørslev's fund for financial support.

PY - 1997/8/1

Y1 - 1997/8/1

N2 - The brain binding kinetics and distribution of the antidepressant venlafaxine, labelled with 11C in the O-methyl position, was studied by PET after intravenous injection in anesthetized pigs. In addition, venlafaxine's action on serotonin (5-HT) uptake was studied in vitro in blood platelets obtain from humans or pigs. Venlafaxine resembled imipramine, paroxetine and citalopram in causing a dose-dependent inhibition of 5-HT uptake in blood platelets from pigs and humans. Venlafaxine-derived radioactivity entered the living brain readily and showed higher binding potentials in diencephalic and telencephalic regions than in cerebellum. Acute administration of an antidepressant drug (i.e. imipramine, citalopram or paroxetine) enhanced the distribution and altered the binding of venlafaxine in certain brain regions. The findings show that [11C]venlafaxine is not an ideal PET radiotracer mainly because of its relatively low binding potentials and its lack of specificity for the 5-HT transporter in living brain.

AB - The brain binding kinetics and distribution of the antidepressant venlafaxine, labelled with 11C in the O-methyl position, was studied by PET after intravenous injection in anesthetized pigs. In addition, venlafaxine's action on serotonin (5-HT) uptake was studied in vitro in blood platelets obtain from humans or pigs. Venlafaxine resembled imipramine, paroxetine and citalopram in causing a dose-dependent inhibition of 5-HT uptake in blood platelets from pigs and humans. Venlafaxine-derived radioactivity entered the living brain readily and showed higher binding potentials in diencephalic and telencephalic regions than in cerebellum. Acute administration of an antidepressant drug (i.e. imipramine, citalopram or paroxetine) enhanced the distribution and altered the binding of venlafaxine in certain brain regions. The findings show that [11C]venlafaxine is not an ideal PET radiotracer mainly because of its relatively low binding potentials and its lack of specificity for the 5-HT transporter in living brain.

KW - Antidepressant binding

KW - Blood platelet

KW - Citalopram

KW - Imipramine

KW - Paroxetine

KW - Pig brain

KW - Serotonin reuptake

KW - Venlafaxine

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U2 - 10.1016/S0924-977X(97)00403-3

DO - 10.1016/S0924-977X(97)00403-3

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AN - SCOPUS:0030612424

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VL - 7

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EP - 200

JO - European Neuropsychopharmacology

JF - European Neuropsychopharmacology

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