Does the prolonged occupancy of M1 receptors by telenzepine protect them against the action of vagally released acetylcholine?
The affinities of telenzepine, pirenzepine and atropine for muscarinic acetylcholine receptors have been determined by receptor binding studies using brain cortex and heart membranes of calf and rat. The ratios of affinities of telenzepine and pirenzepine for the cortical M1 receptors, cortical 'non-M1' receptors and cardiac M2 receptors are 50:5:1 and 80:5:1, respectively. The time course of association of telenzepine and pirenzepine with M1 receptors is similar, whereas the half-times for dissociation are 35 and 2.3 min at 37 degrees C, respectively. In further experiments this slow dissociation rate of telenzepine is shown to be rate-limiting for the occupation of M1 receptors by other ligands. The prolonged occupation of M1 receptors by telenzepine is discussed as a possible protective mechanism against acetylcholine released from vagal nerve fibers.
Schudt
C
C
Department of Biochemistry, Byk Gulden Research Laboratories, Konstanz, FRG.
Auriga
C
C
Birdsall
N J
NJ
Boer
R
R
D000109:Acetylcholine / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000378:metabolism; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism; D002417:Cattle; D066298:In Vitro Techniques; D007700:Kinetics; D019832:N-Methylscopolamine; D010890:Pirenzepine / Q000031:analogs & derivatives* / Q000378:metabolism; D051381:Rats; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism*; D012602:Scopolamine Derivatives / Q000378:metabolism; D014630:Vagus Nerve / Q000378:metabolism
D011976:Receptors, Muscarinic; D012602:Scopolamine Derivatives; C046338:telenzepine; D010890:Pirenzepine; D001285:Atropine; D000109:Acetylcholine; D019832:N-Methylscopolamine