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Low-Dose Amisulpride and Elevation in Serum Prolactin

J Clin Psychiatry 2013;74(6):e558-e560

Substituted benzamides include drugs such as sulpiride, levosulpiride, and amisulpride. These drugs have a biphasic effect on dopaminergic neurotransmission in the central nervous system: at low doses, they increase dopaminergic neurotransmission by preferentially blocking the higher-affinity presynaptic dopamine autoreceptors, and at high doses they decrease dopaminergic neurotransmission by also blocking the lower-affinity dopamine postsynaptic receptors. Paradoxically, low and high doses both raise serum prolactin levels. This is because these drugs do not cross the blood-brain barrier efficiently and because the pituitary lies outside the blood-brain barrier; therefore, what amounts to a low dose for an effect in the brain is a sufficiently high dose outside the blood-brain barrier to block pituitary dopamine receptors and raise prolactin levels. Clinical problems associated with hyperprolactinemia and strategies for the management of hyperprolactinemia associated with low-dose substituted benzamides are briefly discussed.