Abstract
Nafadotride has been proposed as a selective antagonist for the D3 dopamine receptor. This drug has been shown to exhibit selectivity between D2 and D3 dopamine receptors in in vitro assay systems; however, the in vivo D2/D3 selectivity of the compound has not been determined. In this study, protection against inactivation by EEDQ was used as a measure of in vivo occupancy of D2 receptors by behaviorally relevant doses of nafadotride (0.1–10 mg/kg, SC and IP) in adult, male Sprague-Dawley rats. Ex vivo [3H]spiperone binding was then determined in striatal membranes. l-Nafadotride (10 mg/kg) protected 71% of D2 receptors after SC administration; 40% after IP administration. Protection of 13% of D2 receptors was observed at a dose of 3 mg/kg (SC). These data suggest that blockade of D2 receptors contributes to the pharmacological effects of nafadotride when administered at doses above 1 mg/kg (SC) or 3 mg/kg (IP).
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Levant, B., Vansell, N. In Vivo Occupancy of D2Dopamine Receptors by Nafadotride. Neuropsychopharmacol 17, 67–71 (1997). https://doi.org/10.1016/S0893-133X(97)00024-9
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DOI: https://doi.org/10.1016/S0893-133X(97)00024-9
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