Some central effects in mice of compounds related to nicotine

Abstract

Some hydroxy‐, amino‐, and methoxy‐ phenylalkyltrimethylammonium compounds, β‐pyridylmethyl‐ dimethylamine and pyrrolidine, and β‐pyridyl>‐ethyltrimethylammonium, were tested on avoidance learning in mice and their effects were compared with those of (–)‐nicotine. The o‐ and m‐ hydroxybenzyl‐, o‐hydroxyphenethyl‐ and m‐hydroxyphenylpropyl‐ trimethylammonium compounds improved performance; (–)‐nicotine, in one‐quarter of the dose, had similar effects. The m‐ and p‐hydroxyphenethyl‐, o‐hydroxyphenylpropyl‐ and o‐ and p‐ aminobenzyl, and o‐, m‐, and p‐ aminophenethyl‐trimethylammonium compounds impaired performance. (−)‐Nicotine and m‐hydroxyphenylpropyltrimethylammonium appeared also to enhance memory consolidating processes. The central actions of some of the compounds suggest that the possibility that they can penetrate into the central nervous system should not be ruled out even though they are quaternary salts. No correlation was found between the effects of the compounds on avoidance learning and on the frog rectus muscle. Though the differences may be due to differences in access to the central nervous system, it is also possible that the receptors associated with learning processes are different from those in the frog rectus and possibly more specialized. 1970 British Pharmacological Society