D2 Dopaminergic and 5-HT1A Serotonergic Activity of 2-(1-Naphthyl)ethyl- and 2-(2-Naphthyl)ethyl Amines

• Published in: Archiv der Pharmazie (Weinheim) Vol. 336; no. 11; pp. 514 - 522
• Main Authors: Šukalović, V., Roglić, G., Husinec, S., Kostić-Rajaćić, S., Andrić, D., Šošakić, Vukić
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 01.11.2003; WILEY‐VCH Verlag; Wiley-VCH
• Subjects: 2-(1-Naphthyl)ethyl; 2-(2-Naphthyl)ethyl; 5-HT1A; Animals; Binding, Competitive; Biological and medical sciences; Catecholaminergic system; Cattle; Caudate Nucleus - metabolism; Dopamine Agents - chemical synthesis; Dopamine Agents - chemistry; Dopamine Agents - pharmacology; Dopaminergic; Ethylamines - chemical synthesis; Ethylamines - chemistry; Ethylamines - pharmacology; Hippocampus - metabolism; In Vitro Techniques; Medical sciences; Models, Molecular; Molecular Structure; Naphthalenes - chemical synthesis; Naphthalenes - chemistry; Naphthalenes - pharmacology; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Pharmacology. Drug treatments; Radioligand Assay; Receptor, Serotonin, 5-HT1A - metabolism; Receptors, Dopamine D1 - metabolism; Receptors, Dopamine D2 - metabolism; Serotonergic; Serotonin Agents - chemical synthesis; Serotonin Agents - chemistry; Serotonin Agents - pharmacology; Serotoninergic system; Structure-Activity Relationship; 2-(2-Naphthyl)ethyl; Nitrogen heterocycle; Ligand; Central nervous system; Encephalon; Dopaminergic; 5-HT1A Serotonine receptor; Structure activity relation; Bicyclic compound; 5-HT1A; Aromatic compound; Chemical synthesis; Ungulata; Arene; Bovine; Benzene derivatives; D1 Dopamine receptor; Condensed benzenic compound; In vitro; Naphthalene derivatives; D1; D2; Vertebrata; Biological fixation; Mammalia; D2 Dopamine receptor; 2-(1-Naphthyl)ethyl; Benzimidazole derivatives; Biphenyl derivatives; Animal; Tertiary amine; Affinity; Serotonergic; Artiodactyla
• ISSN: 0365-6233; 1521-4184
• DOI: 10.1002/ardp.200300776

Several tertiary 2‐phenylethyl, 2‐(1‐naphthyl)ethyl and 2‐(2‐naphthyl)ethyl amines were synthesized and their binding affinities for dopamine D1, D2 and serotonin 5‐HT1A receptors evaluated in radioligand binding assays. All compounds were inactive in D1 dopamine radioligand binding assay. The 2‐(1‐naphthyl)ethyl analogues expressed a low but significant binding affinity for the D2 and moderate one for the 5‐HT1A receptor subtypes. Most of the remaining compounds expressed binding affinity at the 5‐HT1A receptor subtype but were inactive in D2 receptor binding assay. Based on these results and considering the chemical characteristics of the compounds synthesized and evaluated for dopaminergic and serotonergic activity throughout the present study it can be concluded that hydrophobic type of interaction (stacking or edge‐to‐face) plays a significant role in the formation of receptor‐ligand complexes of 2‐(1‐naphthyl)ethyl amines. This structural motive can be applied to design and synthesize new, more potent dopaminergic/serotonergic ligands by slight chemical modifications.