Comparing the actions of lanicemine and ketamine in depression: key role of the anterior cingulate.

Abstract

Intravenous infusion of lanicemine (formerly AZD6765), a low trapping non-selective N-methyl-D-aspartate (NMDA) receptor antagonist, induces antidepressant effects with a similar time course to ketamine. We investigated whether a single dose lanicemine infusion would reproduce the previously reported decrease in subgenual anterior cingulate cortex (sgACC) activity evoked by ketamine, a potential mechanism of antidepressant efficacy. Sixty un-medicated adults meeting the criteria for major depressive disorder were randomly assigned to receive constant intravenous infusions of ketamine, lanicemine or saline during a 60min pharmacological magnetic resonance imaging (phMRI) scan. Both ketamine and lanicemine gradually increased the blood oxygen level dependent signal in sgACC and rostral ACC as the primary outcome measure. No decreases in signal were seen in any region. Interviewer-rated psychotic and dissociative symptoms were minimal following administration of lanicemine. There was no significant antidepressant effect of either infusion compared to saline. The previously reported deactivation of sgACC after ketamine probably reflects the rapid and pronounced subjective effects evoked by the bolus-infusion method used in the previous study. Activation of the ACC was observed following two different NMDA compounds in both Manchester and Oxford using different 3T MRI scanners, and this effect predicted improvement in mood 1 and 7 days post-infusion. These findings suggest that the initial site of antidepressant action for NMDA antagonists may be the ACC (NCT01046630. A Phase I, Multi-centre, Double-blind, Placebo-controlled Parallel Group Study to Assess the pharmacoMRI Effects of AZD6765 in Male and Female Subjects Fulfilling the Criteria for Major Depressive Disorder; http://clinicaltrials.gov/show/NCT01046630).

• Authors: Darragh Downey, Arpan Dutta, Shane McKie, Gerard R Dawson, Colin T Dourish, Kevin Craig, Mark A Smith, Dennis J McCarthy, Catherine J Harmer, Guy M Goodwin, Steve Williams, J F William Deakin
• Journal: European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology (Eur Neuropsychopharmacol) Vol. 26 Issue 6 Pg. 994-1003 (06 2016) ISSN: 1873-7862 [Electronic] Netherlands
• PMID: 27133029 (Publication Type: Comparative Study, Journal Article, Randomized Controlled Trial)
• Copyright: Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

Chemical References

• AZD6765
• Antidepressive Agents
• Excitatory Amino Acid Antagonists
• Phenethylamines
• Pyridines
• Ketamine

Topics

• Adolescent
• Adult
• Affect
• Antidepressive Agents (administration & dosage, adverse effects, therapeutic use)
• Cross-Over Studies
• Depressive Disorder, Major (diagnostic imaging, drug therapy)
• Double-Blind Method
• Excitatory Amino Acid Antagonists (administration & dosage, adverse effects, therapeutic use)
• Female
• Gyrus Cinguli (drug effects)
• Humans
• Ketamine (administration & dosage, adverse effects, therapeutic use)
• Magnetic Resonance Imaging
• Male
• Middle Aged
• Phenethylamines (administration & dosage, adverse effects, therapeutic use)
• Psychiatric Status Rating Scales
• Pyridines (administration & dosage, adverse effects, therapeutic use)
• Treatment Outcome
• Young Adult