Prevention by drugs of tachyphylaxis at nicotinic receptors in the cat superior cervical ganglion in situ

Abstract

A new copound, AF3 (4-ethyl-6-oxa-1-azatricyclo(4.2.2.0 2,7)dodecan-5-one), and its 4-phenyl analogue, AF6, embodying the structural elements of acetylcholine in a highly rigid rframework, 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 ration 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 tetramethylammonium (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.