New 2-pyridylethylamines with dopaminergic activity: Synthesis and radioligand-binding evaluation

Article abstract of DOI:10.1016/0223-5234(96)88251-1

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 D₁ and D₂ dopamine receptors were evaluated by displacement of [³H]SCH 23390 (D₁ selective) and [³H]spiperone (D₂ 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 D₁ and D₂ receptors. Other compounds bound to the D₁ receptor with higher affinity than to the D₂ receptor. The possibility that the above compounds act as agonists and antagonists at the dopamine D₁ and D₂ receptors is discussed on the basis of guanosine-5'-triphosphate and Na⁺ displacement curves.