Selective labelling of muscarinic M1 receptors in calf superior cervical ganglia by [3H](+/-)-telenzepine.
A method was developed to determine the affinities of antimuscarinic drugs at M1 receptors. [3H](+/-)-Telenzepine served as radioligand in crude preparations of calf superior cervical ganglia and showed high affinity for a single receptor population, consisting of M1 receptors (KD = 1.12 nM). Kinetic experiments showed monophasic association (k1 = 0.017 min-1 nM-1) and dissociation (k-1 = 0.017 min-1) kinetics, the half-life of dissociation being 41 min at 37 degrees C. The kinetic KD value amounted to 1.00 nM. M1 affinities for pirenzepine, methoctramine, hexahydro-sila-difenidol and p-fluoro-hexahydro-sila-difenidol determined in competition experiments were similar to those found in functional studies with M1 receptors in rabbit isolated vas deferens. The binding assay was used to determine the affinities of the (R) and (S) enantiomers of tertiary (trihexyphenidyl, hexahydro-difenidol, hexbutinol, p-fluoro-hexbutinol) and quaternary muscarinic antagonists (trihexyphenidyl methiodide, hexbutinol methiodide). Comparison of results obtained with the rabbit vas deferens suggested that the ionic environment may influence the affinities.
Feifel
R
R
Department of Pharmacology, University of Frankfurt, Main, F.R.G.
Rodrigues de Miranda
J F
JF
Strohmann
C
C
Tacke
R
R
Aasen
A J
AJ
Mutschler
E
E
Lambrecht
G
G
D000818:Animals; D001667:Binding, Competitive; D002417:Cattle; D005724:Ganglia / Q000378:metabolism*; D006207:Half-Life; D066298:In Vitro Techniques; D008297:Male; D009333:Neck; D010880:Piperidines / Q000493:pharmacokinetics; D010890:Pirenzepine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D011817:Rabbits; D011869:Radioligand Assay; D011976:Receptors, Muscarinic / Q000378:metabolism*; D014316:Tritium; D014649:Vas Deferens / Q000378:metabolism
D010880:Piperidines; D011976:Receptors, Muscarinic; C046338:telenzepine; D014316:Tritium; D010890:Pirenzepine; C046773:hexahydrosiladifenidol