Behavioral and neuroendocrine effects of the partial NMDA agonist D-cycloserine in healthy subjects.

The effect of D-cycloserine, a partial agonist of the N-Methyl-D-Aspartate (NMDA) receptor, were assessed in a (neuroendocrine) challenge paradigm to 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.

The partial NMDA agonist D-cycloserine stimulates LH secretion in healthy volunteers.

D-Cycloserine, a partial agonist of the glycine recognition site of the N-methyl-D-aspartate (NMDA) receptor, may serve as a probe for human cerebral NMDA receptor function. Since NMDA receptors are involved in neuroendocrine secretion, changes in pituitary secretion in response to D-cycloserine administration could serve as a model for NMDA receptor activity. The effects of an oral dose of 500 mg D-cycloserine were assessed in a neuroendocrine challenge paradigm in 20 healthy male volunteers, using a double-blind, randomized placebo-controlled crossover design. Luteinizing hormone (LH) and cortisol secretion was studied, since preclinical studies indicate that these hormones increase in response to NMDA receptor stimulation. Furthermore, plasma homovanillic acid (HVA) secretion was studied, as NMDA receptors are suggested to be involved in the regulation of dopaminergic neurotransmission. D-cycloserine was readily absorbed and did not induce side-effects or changes in vital signs and mood scores. D-Cycloserine stimulated LH secretion and induced a significant rise of the area under the plasma concentration time curve of LH. D-Cycloserine did not stimulate cortisol or plasma HVA secretion. These neuroendocrine effects suggest that D-cycloserine may be used to assess human NMDA receptor function in cerebral disorders, such as schizophrenia.