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Title: Carbon-11-cocaine binding compared at subpharmacological and pharmacological doses: A PET study

Abstract

The authors have characterized cocaine binding in the brain to a high-affinity site on the dopamine transporter using PET and tracer doses of [{sup 11}C]cocaine in the baboon in vivo. The binding pattern, however, of cocaine at tracer (subpharmacological) doses may differ from that observed when the drug is taken in behaviorally active doses, particularly since in vitro studies have shown that cocaine also binds to low affinity binding sites. PET was used to compare and characterize [{sup 11}C]cocaine binding in the baboon brain at low subpharmacological (18 {mu}g average dose) and at pharmacological (8000 {mu}g) doses. Serial studies on the same day in the same baboon were used to assess the reproducibility of repeated measures and to assess the effects of drugs which inhibit the dopamine, norepinephrine and serotonin transporters. Time-activity curves from brain and the arterial plasma input function were used to calculate the steady-state distribution volume (DV). At subpharmacological doses, [{sup 11}C]cocaine had a more homogeneous distribution. Bmax/Kd for sub-pharmacological [{sup 11}C]cocaine corresponded to 0.5-0.6 and for pharmacological [{sup 11}C]cocaine it corresponded to 0.1-0.2. Two-point Scatchard analysis gave Bmax = 2300 pmole/g and Kd = 3600 nM. Bmax/Kd for sub-pharmacological doses of [{sup 11}C]cocaine was decreased bymore » cocaine and drugs that inhibit the dopamine transporter, to 0.1-0.2, but not by drugs that inhibit the serotonin or the norepinephrine transporter. None of these drugs changed Bmax/Kd for a pharmacological dose of [{sup 11}C]cocaine. At subpharmacological doses, [{sup 11}C]cocaine binds predominantly to a high-affinity site on the dopamine transporter. 36 refs., 4 figs., 5 tabs.« less

Authors:
; ;  [1]
  1. Brookhaven National Lab., Upton, NY (United States)
Publication Date:
Research Org.:
Brookhaven National Lab. (BNL), Upton, NY (United States)
OSTI Identifier:
258972
DOE Contract Number:  
AC02-76CH00016
Resource Type:
Journal Article
Journal Name:
Journal of Nuclear Medicine
Additional Journal Information:
Journal Volume: 36; Journal Issue: 7; Other Information: PBD: Jul 1995
Country of Publication:
United States
Language:
English
Subject:
55 BIOLOGY AND MEDICINE, BASIC STUDIES; COCAINE; METABOLISM; RADIOPHARMACEUTICALS; RECEPTORS; POSITRON COMPUTED TOMOGRAPHY

Citation Formats

Volkow, N D, Fowler, J S, Logan, J, and State Univ. of New York, Stony Brook, NY. Carbon-11-cocaine binding compared at subpharmacological and pharmacological doses: A PET study. United States: N. p., 1995. Web.
Volkow, N D, Fowler, J S, Logan, J, & State Univ. of New York, Stony Brook, NY. Carbon-11-cocaine binding compared at subpharmacological and pharmacological doses: A PET study. United States.
Volkow, N D, Fowler, J S, Logan, J, and State Univ. of New York, Stony Brook, NY. 1995. "Carbon-11-cocaine binding compared at subpharmacological and pharmacological doses: A PET study". United States.
@article{osti_258972,
title = {Carbon-11-cocaine binding compared at subpharmacological and pharmacological doses: A PET study},
author = {Volkow, N D and Fowler, J S and Logan, J and State Univ. of New York, Stony Brook, NY},
abstractNote = {The authors have characterized cocaine binding in the brain to a high-affinity site on the dopamine transporter using PET and tracer doses of [{sup 11}C]cocaine in the baboon in vivo. The binding pattern, however, of cocaine at tracer (subpharmacological) doses may differ from that observed when the drug is taken in behaviorally active doses, particularly since in vitro studies have shown that cocaine also binds to low affinity binding sites. PET was used to compare and characterize [{sup 11}C]cocaine binding in the baboon brain at low subpharmacological (18 {mu}g average dose) and at pharmacological (8000 {mu}g) doses. Serial studies on the same day in the same baboon were used to assess the reproducibility of repeated measures and to assess the effects of drugs which inhibit the dopamine, norepinephrine and serotonin transporters. Time-activity curves from brain and the arterial plasma input function were used to calculate the steady-state distribution volume (DV). At subpharmacological doses, [{sup 11}C]cocaine had a more homogeneous distribution. Bmax/Kd for sub-pharmacological [{sup 11}C]cocaine corresponded to 0.5-0.6 and for pharmacological [{sup 11}C]cocaine it corresponded to 0.1-0.2. Two-point Scatchard analysis gave Bmax = 2300 pmole/g and Kd = 3600 nM. Bmax/Kd for sub-pharmacological doses of [{sup 11}C]cocaine was decreased by cocaine and drugs that inhibit the dopamine transporter, to 0.1-0.2, but not by drugs that inhibit the serotonin or the norepinephrine transporter. None of these drugs changed Bmax/Kd for a pharmacological dose of [{sup 11}C]cocaine. At subpharmacological doses, [{sup 11}C]cocaine binds predominantly to a high-affinity site on the dopamine transporter. 36 refs., 4 figs., 5 tabs.},
doi = {},
url = {https://www.osti.gov/biblio/258972}, journal = {Journal of Nuclear Medicine},
number = 7,
volume = 36,
place = {United States},
year = {Sat Jul 01 00:00:00 EDT 1995},
month = {Sat Jul 01 00:00:00 EDT 1995}
}