Comparison of the effects of ketamine and memantine on prolactin and cortisol release in men. a randomized, double-blind, placebo-controlled trial.
N-methyl D-aspartate (NMDA)-antagonists decrease neurotoxicity by inhibiting Ca2+ influx which is of interest for the treatment of acute cerebrovascular insults and chronic neurodegenerative disorders. Currently, there is no surrogate marker for quantification of NMDA-receptor-mediated drug effects, which hampers dose-finding clinical studies. As prolactin and cortisol liberation is in part influenced through NMDA-receptors we investigated whether the elevation of prolactin or cortisol plasma levels is a class effect of NMDA-antagonists and might be an appropriate marker for studying NMDA-antagonistic potency. Fifteen healthy male volunteers participated in this placebo-controlled, randomized, three-way crossover trial. Ketamine (0.5mg/kg), memantine (0.16 mg/kg; i.e., a well tolerated standard dose) or placebo were infused over 60 min. Ketamine increased serum prolactin and cortisol levels (p < 0.001), whereas memantine and placebo did not affect hormone levels. Further studies are needed to define whether higher doses of memantine or other NMDA antagonists can induce hormone release.
Department of Clinical Pharmacology, Vienna University School of Medicine, Vienna, Austria.
N
N
Hergovich
E
E
Singer
E
E
Agneter
H G
HG
Eichler
U
U
Graselli
C
C
Simhandl
B
B
Jilma
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D018592:Cross-Over Studies; D004361:Drug Tolerance / Q000502:physiology; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage* / Q000009:adverse effects; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D007649:Ketamine / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008559:Memantine / Q000008:administration & dosage* / Q000009:adverse effects; D009410:Nerve Degeneration / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000009:adverse effects; D011388:Prolactin / Q000097:blood*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000378:metabolism*
D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; D007649:Ketamine; D011388:Prolactin; D008559:Memantine; D006854:Hydrocortisone