PHARMACOLOGICAL PROFILE OF NON-HYDROXYLATED AND ETHER DERIVATIVES OF THE POTENT D2-SELECTIVE AGONIST N-0437
作者： Johanna M. Jansen , Izaak den Daas , Hans Rollema , Pieter J. Swart , Pieter G. Tepper
DOI: 10.1007/BF00168600
关键词: Striatum 、 Dopaminergic 、 Agonist 、 Dopamine 、 Internal medicine 、 Dopamine agonist 、 Dopamine receptor 、 Amphetamine 、 Nigrostriatal pathway 、 Endocrinology 、 Chemistry
摘要: Derivatives of the potent dopamine D2-selective agonist 2-(N-propyl-N-2-thienylethylamino)-5-hydroxytetralin (N-0437) were designed, aimed at producing drugs with less sensitivity towards metabolic inactivation (in particular glucuronidation 5-OH position). Since aminotetralins a 5-methoxy substituent or lacking 5-hydroxy group have been reported to retain dopaminergic activity, non-5-hydroxylated N-0437 (N-0918) and two ethers [5-methoxyN-0437 (N-0724) 5-cyclopentoxy-N-0437 (N-0953)] prepared tested. Three indices for activity central receptors are considered: (1) displacement (3 H)-SCH-23390 (3H)-spiperone from calf caudate membranes, (2) effects on release metabolism in striatum freely moving rats after systemic intrastriatal administration as assessed by brain microdialysis, (3) ability elicit contralateral turning unilateral 6-OH-dopamine lesion nigrostriatal pathway. In order differentiate between direct activation, plasma levels N-0724 N-0953 measured.
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