Prevention by drugs of tachyphylaxis at nicotinic receptors in the cat superior cervical ganglion in situ.
A new compound, AF3 (4-ethyl-6-oxa-1-azatricyclo)4.2.2.02,7)dodecan-5-one), and its 4-phenyl analogue, AF6, embodying the structural elements of acetylcholine in a highly rigid framework, were shown to evoke nicotine-like responses in the nictitating membrane (NM) and blood pressure when applied to the superior cervical ganglion in anaesthetized cats. In this respect, their equiactive molar ratio was (nicotine : 1),20-30. However, at doses that were too low to evoke any response, AF3 appeared to potentiate the responses to nicotine or tetra-methylammonium (TMA) by preventing or abolishing tachyphylaxis to the two latter drugs, the effect being dose-dependent with AF3. DMPP which produces much less tachyphylaxis, or preganglionic nerve stimulation, was little or not potentiated in presence of AF3. It is proposed that potentiation to nicotine or TMA occurs following occupancy by AF3 of a regulatory subsite, thereby preventing further access to it by nicotine or TMA. In this respect, AF3 plays the role of a "neutral" molecule.
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002415:Cats; D003183:Complement C6 / Q000494:pharmacology; D004246:Dimethylphenylpiperazinium Iodide / Q000494:pharmacology; D005260:Female; D005727:Ganglia, Spinal / Q000187:drug effects*; D005731:Ganglionic Stimulants; D008297:Male; D009469:Neuromuscular Junction / Q000187:drug effects; D009538:Nicotine / Q000494:pharmacology; D009541:Nictitating Membrane / Q000187:drug effects; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D011950:Receptors, Cholinergic / Q000187:drug effects*; D011978:Receptors, Nicotinic / Q000187:drug effects*; D013618:Tachyphylaxis
D003183:Complement C6; D005731:Ganglionic Stimulants; D000644:Quaternary Ammonium Compounds; D011950:Receptors, Cholinergic; D011978:Receptors, Nicotinic; D004246:Dimethylphenylpiperazinium Iodide; D009538:Nicotine; D001285:Atropine