Rodent biodistribution and metabolism of tritiated 4-DAMP, a M3 subtype-selective cholinoceptor ligand.
The biodistribution of [3H]4-DAMP (a M3-selective cholinoceptor antagonist) was studied in rats which had received either saline or saline containing atropine (to block cholinoceptors). Specific binding of the radioligand was observed in the urinary bladder, ileum, pancreas, stomach, submandibular gland and trachea. Maximal ratios of total-to-non-specific uptake reached values of 1.8 (trachea), 3.2 (bladder), 4.0 (stomach), 4.8 (ileum), 6.6 (pancreas) and 6.9 (submandibular gland) at 5-10 min post-injection; this rank order reflects the tissue densities of M3 cholinoceptors, 4-DAMP did not bind to blood cells and it was rapidly cleared from the circulation (> 90% with a half-life of 0.2 min, the remainder with a half-life of 9.4 min). Labelled metabolites appeared within 5 min in plasma, but metabolite uptake by the target organs was low (< 15% of total radioactivity 40 min post-injection). Although 4-DAMP binds to M3-cholinoceptors in vivo, its potential use as a radiopharmaceutical appears limited since the compound does not cross the blood-brain barrier and it does not show measurable specific binding in airways.
van Waarde
A
A
PET Center, University Hospital, Groningen, The Netherlands.
Visser
G M
GM
Visser
T J
TJ
Bouwer
J
J
Paans
A M
AM
Vaalburg
W
W
D000818:Animals; D008297:Male; D018727:Muscarinic Antagonists / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D010880:Piperidines / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution; D014316:Tritium
D018727:Muscarinic Antagonists; D010880:Piperidines; D014316:Tritium; C042375:4-diphenylacetoxy-1,1-dimethylpiperidinium