Acute Antagonism of Dopamine D2-like Receptors by Amisulpride: Effects on Hormone Secretion in Healthy Volunteers

Amisulpride is a selective D2-like dopamine receptor antagonist with a high affinity for the cloned D2 and D3 receptors. At low doses it may improve depressive and negative schizophrenic symptoms whereas antipsychotic effects on positive schizophrenic symptomatology require higher dosages. Acute endocrine effects were studied for two doses of amisulpride with regard to the daytime secretion of prolactin, thyroidea stimulating hormone (TSH), growth hormone (GH), luteinizing hormone (LH) and cortisol. Amisulpride was administered i.v. to eight healthy male volunteers in a single-blind trial under a randomized cross-over, placebo-controlled design using doses of 20 mg or 100 mg, or saline. The drug was injected at 09:00 h, and plasma samples were withdrawn from 08:30 h to 16:00 h at intervals of 15 and 30 min, respectively. At both dosages, prolactin was significantly elevated to the eight- to ten-fold of baseline levels. Likewise, a significant 50% elevation of TSH concentrations with a trend to a greater increase under the 100 mg dose was observed. Plasma levels of LH and cortisol were not significantly affected by amisulpride. With regard to GH secretion, there was a trend to a decrease only with the 20 mg dose. These results indicate that the neuroendocrinological side-effect profile of acute amisulpride administration may be similar to conventional neuroleptics, and that there are only minor dose-dependent differential effects on hormone secretion in the dose range investigated.