BBB transport and rapid tissue binding of cyclofoxy: comparison of active and inactive enantiomers. Academic Article uri icon

Overview

abstract

  • The "rapid-phase" brain distribution of 3H-labeled enantiomers of the opiate receptor antagonist cyclofoxy (CF), receptor active (-) and inert (+) forms, was measured during 20- to 180-s intravenous infusion in rats. [14C]iodoantipyrine was coinfused during these experiments to obtain a simultaneous measure of blood flow. The influx clearance (K1) across the blood-brain barrier (BBB) and the rapid binding equilibrium constant (Keq) were estimated in different brain regions for both enantiomers (2-compartmental model); a possible receptor binding process (k3) was also examined for (-)-CF (3-compartment model). K1 (0.46-0.91 ml.min-1.g-1), the capillary permeability-surface area product (PS; 0.75 approximately 1.4 ml.min-1.g-1) and the tissue extraction fraction (E; 0.6-0.7) were found to be identical for both enantiomers in the nonreceptor binding model; Keq was identical in cerebellum but larger for (-)-CF in other brain structures. The difference in Keq between the enantiomers (2-compartment model) correlated with the rank order of opiate receptor density observed in vitro and in vivo. These results suggest that concomitant use of (-)-CF and (+)-CF will be useful for in vivo receptor binding analyses.

publication date

  • October 1, 1990

Research

keywords

  • Blood-Brain Barrier
  • Naltrexone

Identity

Scopus Document Identifier

  • 0025188592

Digital Object Identifier (DOI)

  • 10.1152/ajpheart.1990.259.4.H1278

PubMed ID

  • 2221131

Additional Document Info

volume

  • 259

issue

  • 4 Pt 2