Barrass_1968_Br.J.Pharmacol_34_345

1. Several amino-acid esters and amides have been prepared and their toxicological and pharmacological properties have been investigated. Some of the quaternary esters and amides were lethal to mice at doses below 1 mg/kg; this lethality was usually associated with high nicotinic activity. None of the compounds showed high muscarinic activity.2. The cause of death was asphyxia due to paralysis of the respiratory muscles, but at higher doses there was also failure of the medullary respiratory centre.3. Administration of sub-lethal doses of nicotine to mice was shown to protect the animals from subsequent lethal doses of nicotine. The amino-acid esters did not share this property, nor was there any cross-protection between nicotine and these esters.4. The possible nature of the nicotinic receptor is discussed with reference to these compounds and other known nicotinic agents. A tentative suggestion is made that nicotinic activity can result from a two-point interaction between the drug and the receptor.