NEW 2-PYRIDYLETHYLAMINES WITH DOPAMINERGIC ACTIVITY - SYNTHESIS AND RADIOLIGAND-BINDING EVALUATION

In order to determine whether the pyridine nucleus could replace the catechol moiety of the neurotransmitter dopamine or the phenol ring of the dopaminergic pharmacophore m-hydroxyphenylethylamine, the 2-(3-pyridyl)ethylamine 7, 2-(4-pyridyl)ethylamine 8, 2-(2-hydroxy-4-pyridyl) ethylamine 10 and their N,N-di-n-propyl- and N-n-propyl-N-2-phenylethyl derivatives were synthesized. The affinities of the new compounds for D-1 and D-2 dopamine receptors were evaluated by displacement of [H-3]SCH 23390 (D-1 selective) and [H-3]spiperone (D-2 selective) on rat neostriatum sections. The 2-(4-pyridyl)ethylamine 8 and its N,N-di-n-propyl derivative 18 showed the same affinity for the D-1 and D-2 receptors. Other compounds bound to the D-1 receptor with higher affinity than to the D-2 receptor. The possibility that the above compounds act as agonists and antagonists at the dopamine D-1 and D-2 receptors is discussed on the basis of guanosine-5'-triphosphate and Na+ displacement curves.