Kinetic analysis of muscarinic receptors in human brain and salivary gland
in vivo..
Hiramatsu, Yukiharu, William C. Eckelman, Jorge A. Carrasquillo, Robert S.
Miletich, Ingrid, H. Valdez, Regina H. M. Kurrasch, Alice A. Macynski, Chang
H. Paik, Ronald D., Neumann, and Bruce. J. Baum.
Clinical Investigations and Patient Care Branch, National Institute of
Dental Research, Nuclear Medicine Department and Positron Emission Tomography
Department, Clinical Center, National Institutes of Health, Bethesda, MD
20892
APStracts 2:0013R, 1995.
Kinetic analysis of muscarinic receptors in human brain and salivary gland in
vivo. Am. J. Physiol (Regulatory, Integrative Comp. Physiol.) Previous
studies in rats have suggested that the muscarinic acetylcholine receptor
(mAChR) antagonist (S)-3-quinuclidinyl (S)-[123I]-4-iodobenzilate,
(SS)-IQNB, may be useful for the in vivo evaluation of mAChRs in humans as a
control for the higher affinity compound (RR)-IQNB. We have directly tested
this hypothesis and examined the distribution of mAChRs in brain regions and
parotid glands of healthy human volunteers in vivo using (RR)-and (SS)-IQNB
(relatively high and low affinity antagonists, respectively), planar imaging,
and pharmacokinetic analysis. This is the first study in vivo of mAChRs in
humans that has employed stereoisomeric ligands and metabolic analysis to
determine specific receptor binding. We observed that (SS)-IQNB showed much
faster clearance from blood than (RR)-IQNB and different metabolite profiles.
Also, the transport kinetics of the enantiomers were different. The estimated
binding potential (_Bmax/Kd) of (RR)-IQNB in two cortical regions was
highest, intermediate in parotid gland, and lowest in cerebellum. The
aggregate results show that in humans (SS)-IQNB does not act as an ideal,
general probe to measure the nonspecific IQNB distribution. However, (RR)
-IQNB does appear to have value when used for studies of human brain mAChRs.
Received 7 October 1994; accepted in final form 9 January 1995.
APS Manuscript Number R584-4.
Article publication pending Am. J. Physiol. (Regulatory Integrative Comp.
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 25 February 1995.