Behavioral and Neuroendocrine Effects of the Partial NMDA Agonist D-cycloserine in Healthy Subjects

The effects of D-cycloserine, a partial agonist of the N-Methyl-D-Aspartate (NMDA) receptor, were assessed in a (neuroendocrine) challenge paradigm to examine NMDA systems in male healthy volunteers, using a double-blind, placebo-controlled crossover design. Oral D-cycloserine (15, 50, and 150 mg) was readily absorbed and its plasma concentration increased dose-dependently. Behavioral and hormonal responses were measured for 240 minutes after administration of the drug. D-cycloserine was well tolerated and did not induce side-effects according to the Visual Analog Scales (VAS), the Brief Psychiatric Rating Scale (BPRS) and the Adverse Events Checklist (AEC) & codes. D-cycloserine failed to elicit a neuroendocrine response as evaluated by cortisol, prolactin, and luteinizing hormone (LH) plasma levels. The present result suggests that D-cycloserine can readily be administered to healthy volunteers but that, in the dosages used, neuroendocrine secretion fails to serve as a model for testing NMDA receptor function in humans.