Comment on: 'Effects of a novel mGlu(2/3) receptor agonist prodrug, LY2140023 monohydrate, on central monoamine turnover as determined in human and rat cerebrospinal fluid' (Lowe S, Dean R, Ackermann B, Jackson K, Natanegara F, Anderson S, Eckstein J, Yuen E, Ayan-Oshodi M, Ho M, McKinzie D, Perry K, Svensson K, Psychopharmacology, 2012).

摘要

The paper by Lowe et al. (2012) reports that the glutamate agonist LY404,039 increases the turnover of brain dopamine, but the paper wrongly concludes that this drug has no affinity for dopamine receptors. In fact, this drug is known to inhibit the binding of ligands to dopamine D2 and D3 receptors. For example, this drug inhibits the binding of [~3H]domperidone, as well as [~3H](+)PHNO, to the functional high-affinity state of cloned dopamine D2 receptors (D2High) and rat striatal tissues with dissociation constants between 8 and 13 nM (Seeman and Guan 2009b). Moreover, this drug inhibits the binding of these two ligands at rat dopamine D3 receptors (Seeman and Guan 2009b). In addition, this drug stimulates the incorporation of [~(35)S]GTP-gamma-S into dopamine D2 receptors with 50 % incorporation occurring at 80 nM (Seeman and Guan 2009b). Therefore, these direct actions of LY404,039 indicate an agonist action or a partial agonist action on dopamine D2 receptors, which readily accounts for the increased turnover of dopamine found by Lowe et al. (2012).