The in vitro dissociation kinetics of (R,R)-[125I]4IQNB is reflected in the in vivo washout of the radioligand from rat brain

Life Sci. 1992;50(9):629-37. doi: 10.1016/0024-3205(92)90249-o.

Abstract

We have determined the kinetics of dissociation of (R)-3-Quinuclidinyl (R)-4-[125I]Iodobenzilate ((R,R)-[125I]4IQNB) from muscarinic acetylcholine receptor preparations from the cortex, hippocampus, caudate/putamen, thalamus, pons and colliculate bodies. The dissociation curves are well described by a biexponential function and are consistent with subtype selectivity favoring slow dissociation from the M1, M3, and M4 receptors with a 20-fold faster dissociation rate for the M2 receptor. Following intravenous injection, (R,R)-[125I]4IQNB binds to receptor in the rat brain in concentrations which reflect the receptor concentration present in a structure. We determined the extent of radioligand present at two times, 2 and 24 hrs, as an indication of the relative proportions of m-AChR which exhibits rapid vs. slow dissociation of (R,R)-[125I]4IQNB. A good correlation between in vitro and in vivo results suggests that the relative populations of receptor subtypes can be imaged using in vivo pharmacokinetics of (R,R)-[125I]4IQNB.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Autoradiography
  • Brain / metabolism*
  • In Vitro Techniques
  • Kinetics
  • Quinuclidinyl Benzilate / analogs & derivatives*
  • Quinuclidinyl Benzilate / metabolism
  • Radioligand Assay
  • Rats
  • Rats, Inbred Strains
  • Receptors, Muscarinic / metabolism

Substances

  • Receptors, Muscarinic
  • quinuclidinyl benzilate receptor
  • Quinuclidinyl Benzilate
  • 3-quinuclidinyl-4-iodobenzilate