ACUTE ANTAGONISM OF DOPAMINE D-2-LIKE RECEPTORS BY AMISULPRIDE - EFFECTS ON HORMONE-SECRETION IN HEALTHY-VOLUNTEERS

Amisulpride is a selective D-2-like dopamine receptor antagonist with a high affinity for the cloned D-2 and D-3 receptors. At low;loses it may improve depressive and negative schizophrenic symptoms whereas ant ipsychotic effects on positive schizophrenic symptomatology require hi gher dosages. Acute endocrine effects were studied for two doses of am isulpride 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 m ale volunteers in a single-blind trial under a randomized cross-over, placebo-controlled design using doses of 20 mg or 100 mg, or saline. T he drug was injected at 09:00 h, and plasma samples were withdrawn fro m 08:30 h to 16:00 h at intervals of 15 and 30 min, respectively. At b oth 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 do se was observed. Plasma levels of LH and cortisol were not significant ly affected by amisulpride. With regard to GH secretion, there was a t rend to a decrease only with the 20 mg dose. These results indicate th at the neuroendocrinological side-effect profile of acute amisulpride administration may be similar to conventional neuroleptics, and that t here are only minor dose-dependent differential effects on hormone sec retion in the dose range investigated.