Action of tacrine on muscarinic receptors in rat intestinal smooth muscle.
1. The reversible cholinesterase inhibitor, tacrine (THA) was examined against the contractions of rat duodenum to acetylcholine and carbachol (cholinesterase resistant). 2. Tacrine (10(-6) M) showed a similar behaviour to physostigmine (10(-6) M), changing the characters of the concentration-response curve to Ach. The contractual responses were shifted to the left at low concentrations of ACh to reveal a bell-shaped curve with declaring contradictions at high concentrations of ACh. 3. Antagonism by atropine (10(-8) M) was reduced in the presence of tacrine (10.54, dose-ratio) compared with the shift of the curve in the absence of tacrine (73.9, dose-ratio). The declining phase of the concentration-response curve to ACh was also antagonized by atropine. 4. Further evidence for muscarininc receptor antagonism by tacrine was a small rightward shift of the concentration-response curve for carbachol, an agonist immune to cholinesterase. 5. This study has shown that tacrine acts both as a cholinesterase inhibitor and muscarinic antagonist on rat intestinal smooth muscle.
Becerra
M A
MA
Departamento de Farmacología, Facultad de Farmacia, Universidad de Sevilla, Profesor García-Gonzalez s/n, 41012 Sevilla, Spain.
Herrera
M D
MD
Marhuenda
E
E
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004386:Duodenum / Q000187:drug effects; D005260:Female; D066298:In Vitro Techniques; D007422:Intestines / Q000187:drug effects*; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000187:drug effects*; D013619:Tacrine / Q000494:pharmacology*
D002800:Cholinesterase Inhibitors; D018727:Muscarinic Antagonists; D011976:Receptors, Muscarinic; D013619:Tacrine; D002217:Carbachol; D000109:Acetylcholine