Specificity of some ganglion stimulants.
1. The specificity of several ganglion stimulants has been tested on the isolated guinea-pig ileum by measuring the dose ratios produced by concentrations of hexamethonium.2. Most ganglion stimulants are also active at postganglionic receptors, some as blocking agents (for example, lobeline and dimethylphenylpiperazinium), others as agonists (for example, o-aminophenethyltrimethylammonium and, to a lesser extent, nicotine). The most specific ganglion stimulant, with the least activity at postganglionic receptors, was p-aminophenethyltrimethylammonium.3. The affinity constants of lobeline and dimethylphenylpiperazinium for the muscarine sensitive receptors in the guinea-pig ileum are 1.05 x 10(6) and 3.71 x 10(4), respectively.4. The antagonism of p-aminophenethyltrimethylammonium by hexamethonium gave results consistent with competition up to dose ratios of about 20. Such results could also be obtained if the antagonism were non-competitive, however, provided large responses could be obtained with less than about 5% of the receptors in the ganglia activated. The affinity constant of hexamethonium is about 2.6 x 10(5).5. It is suggested that the affinity of hexamethonium can largely be ascribed to hydrophobic bonding.
D000818:Animals; D001337:Autonomic Agents / Q000494:pharmacology*; D005730:Ganglionic Blockers / Q000494:pharmacology; D005731:Ganglionic Stimulants / Q000494:pharmacology; D006168:Guinea Pigs; D006584:Hexamethonium Compounds / Q000494:pharmacology; D007082:Ileum / Q000187:drug effects*; D066298:In Vitro Techniques; D008120:Lobeline / Q000494:pharmacology; D009538:Nicotine / Q000494:pharmacology; D010627:Phenethylamines / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011955:Receptors, Drug; D013268:Stimulation, Chemical
D001337:Autonomic Agents; D005730:Ganglionic Blockers; D005731:Ganglionic Stimulants; D006584:Hexamethonium Compounds; D010627:Phenethylamines; D010879:Piperazines; D011955:Receptors, Drug; D009538:Nicotine; D008120:Lobeline