Amino-containing local anaesthetics of bifunctional structure. Activity and structure dependence

A study was carried out on terminal, infiltrational and conductive anaesthetic activity of new aliphatic-aromatic aminoamides, C6H5CR(NHCOR'') - (CH2)nNR'2, which are the result of reaction between corresponding aminocarbinoles with nitriles in the presence of concentrated sulphuric acid. Terminal anaesthesia was checked on the rabbit eye cornea. Infiltrational anaesthesia was performed on guinea-pigs, conductive anaesthesia on frogs. A comparison of data on the local anaesthetic activity of aminoamides, aminoketones and aminoesters showed that aminoamides display a larger activity than aminoketones and are on the same scale as aminoesters. The choice of aminoamides made it possible to show the influence of various features of structure (lengths of hydrocarbon chain between functional groups, the nature of substitutes in the functional groups) on the local anaesthetic action of the preparations under study. It was proved that the increase of distance between the functional groups appreciably intensifies local anaesthetic activity. Moreover, substitution of the para and meta position by the benzene ring in the amide group leads to an increase of the anaesthetic effect.