Compounds antagonistic to norepinephrine retention by rat brain homogenates

Abstract

Several compounds, either catechols, or amines with a phenyl-alkyi configuration or an approximation of it, diminished the ability of rat brain homogenates to retain in vitro, [ 3H]norepinephrine accumulated in brain tissues in vivo following intracisternal injection. Among the active compounds were several phenethylamine derivatives, including β-phenethylamine, β-phenylthanolamine, amphetamine, p-tyramine, and octopamine: compounds which are indirectly acting amines or putative false transmitters. Presence of a β-hydroxyl group may increase activity somewhat. An aliphatic side chain of 2 or 3 carbons was important for activity of aromatic amines. Also active were serotonin, several catecholamines, and 6-hydroxy-dopamine, as well as the catechol amino acid, l-dopa. Deaminated catechols, including dihydroxymandelic acid and dihydroxyphenylacetic acid were active at higher concentrations only. Catechols were inactivated by O-methylation. Certain non-aromatic cyclic amines, including amantadine, were active. Aliphatic amines and Ω-hydroxyl-amines of appropriate carbon chain length had some activity. Acetylcholine (with eserine) was inactive. That the active compounds may have significant central nervous system actions based partially on their ability to interfere with catecholamine re-uptake or storage, is suggested.