The affinity, selectivity and biological activity of telenzepine enantiomers.
The binding of the enantiomers of telenzepine to muscarinic receptor subtypes present in guinea-pig cerebral cortex, myocardium and salivary glands has been examined. The (+) enantiomer is more potent in all assays and exhibits a greater selectivity than the (-) enantiomer for the different receptor subtypes. As a consequence, the enantiomeric potency ratio varies from ca. 400 (cortical 'M1' receptors) to ca. 50 (cardiac receptors). In functional assays in vitro in the rabbit vas deferens and rat atria, the affinity constants and enantiomeric potency ratios for the two isomers agree with those found for the appropriate muscarinic receptor subtype in binding assays. A high enantiomeric potency ratio, 180, is found in vivo for the ability of the telenzepine enantiomers to inhibit the production of lesions in the modified Shay rat preparation. The data are compatible with the blockade of M1 receptors by (+)-telenzepine being responsible for this action of telenzepine and would tend to exclude the possibility that the anti-ulcer action of telenzepine is mediated via a muscarinic or non-muscarinic action of the (-) enantiomer.
Schudt
C
C
Department of Pharmacology, Byk Gulden Research Laboratories, Konstanz, F.R.G.
Boer
R
R
Eltze
M
M
Riedel
R
R
Grundler
G
G
Birdsall
N J
NJ
D008455:(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride / Q000494:pharmacology; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005744:Gastric Acid / Q000378:metabolism; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium / Q000378:metabolism; D010276:Parasympatholytics / Q000378:metabolism / Q000494:pharmacology*; D010890:Pirenzepine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism; D012469:Salivary Glands / Q000187:drug effects / Q000378:metabolism; D013237:Stereoisomerism; D014649:Vas Deferens / Q000378:metabolism
D010276:Parasympatholytics; D011976:Receptors, Muscarinic; C046338:telenzepine; D010890:Pirenzepine; D008455:(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride