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Ionization Behavior and Ionization‐Dependent Conformation of Raclopride, a Dopamine D 2 Receptor Antagonist
Author(s) -
Carrupt PierreAlain,
Tsai RueyShiuan,
Tayar Nabil El,
Testa Bernard,
de Paulis Tomas,
Högberg Thomas
Publication year - 1991
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.19910740506
Subject(s) - chemistry , raclopride , intramolecular force , hydrogen bond , stereochemistry , antagonist , ionization , dopamine , ionic bonding , potentiometric titration , computational chemistry , receptor , ion , organic chemistry , molecule , biochemistry , neuroscience , biology
Raclopride, an antipsychotic 6‐methoxysalicylamide (= 2‐hydroxy‐6‐methoxybenzamide) derivative, was shown by titrimetry and UV‐pholometry to exist in zwitterionic form at physiological pH. Calculations revealed that the neutral and zwitterionic forms differ considerably in their conformational behavior, the latter form being energetically favored by an intramolecular phenolate–ammonium ionic bond. These findings indicate that raciopride and other halogenated 6‐melhoxysalicylamides with a highly acidic phenolic group may not resemble other ortho ‐methoxybenzamides in their stereoelectronic structure and mode of binding to the dopamine D 2 receptor.