Interaction of telenzepine with muscarinic receptors in mammalian sympathetic ganglia.
The interaction of the antimuscarinic drug telenzepine with muscarinic receptors was studied in rabbit and rat isolated superior cervical sympathetic ganglia. Radioligand binding demonstrated two muscarinic receptor sites in rabbit ganglia, with the characteristics of M1- and M2-receptors. Telenzepine bound to the M1 sites with a KI of 0.94 nmol/l and to the M2 sites with a KI of 17.8 nmol/l; the corresponding values for pirenzepine were 18.6 and 588 nmol/l; for AF-DX 116 the values were 891 and 33 nmol/l respectively. [3H]Telenzepine dissociated from the M1-receptors with a half time of 46 min at 37 degrees C. Electrophysiological experiments demonstrated that telenzepine reduced the amplitude of the extracellularly recorded slow excitatory postsynaptic potential and the slow inhibitory postsynaptic potential (ED50: 38 and 253 nmol/l respectively). In rat ganglia, application of muscarine or the M1-receptor agonist McN-A-343 increased the amplitude of submaximal population action potentials. This facilitation of synaptic transmission was potently blocked by telenzepine and pirenzepine but only weakly by AF-DX 116 (ED50: ca. 30, 150 and 20 mumol/l, respectively). It is concluded that telenzepine blocks the generation of the slow excitatory postsynaptic potential and the excitatory action of muscarine and McN-A-343 via an action on muscarinic M1-receptors.
Department of Pharmacology, Byk Gulden Pharmaceuticals, Konstanz, F.R.G.
M
M
Galvan
R
R
Boer
C
C
Schudt
D000818:Animals; D001667:Binding, Competitive; D004305:Dose-Response Relationship, Drug; D005728:Ganglia, Sympathetic / Q000187:drug effects*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009116:Muscarine / Q000378:metabolism / Q000494:pharmacology; D010276:Parasympatholytics / Q000378:metabolism / Q000494:pharmacology*; D010890:Pirenzepine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors
D010276:Parasympatholytics; D011976:Receptors, Muscarinic; C046338:telenzepine; D010890:Pirenzepine; D009116:Muscarine; C048593:otenzepad