Lanicemine: A low-trapping NMDA channel blocker produces sustained antidepressant efficacy with minimal psychotomimetic adverse effects

Molecular Psychiatry

Volumn 19, Issue 9, 2014, Pages 978-985

  Sanacora, G ^a   Smith, M A ^b   Pathak, S ^b   Su, H L ^b   Boeijinga, P H ^c   McCarthy, D J ^b   Quirk, M C ^b  

^a YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b ASTRAZENECA   (United Kingdom)

^c FORENAP   (France)

Author keywords

antidepressant efficacy; lanicemine; NMDA channel blocker

Indexed keywords

ANTIDEPRESSANT AGENT; KETAMINE; LANICEMINE; PLACEBO; PSYCHEDELIC AGENT; N METHYL DEXTRO ASPARTIC ACID RECEPTOR; PHENETHYLAMINE DERIVATIVE; PYRIDINE DERIVATIVE;

ANIMAL EXPERIMENT; ANTIDEPRESSANT ACTIVITY; ARTICLE; CONSTIPATION; CONTROLLED STUDY; DIARRHEA; DIZZINESS; DRUG EFFICACY; DRUG SAFETY; DRUG TOLERABILITY; ELECTROENCEPHALOGRAM; ELECTROENCEPHALOGRAPHY; ELEVATED BLOOD PRESSURE; FATIGUE; HEADACHE; HUMAN; HYPESTHESIA; MAJOR DEPRESSION; MALE; NAUSEA; NONHUMAN; PHASE 2 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; PSYCHOPHARMACOLOGY; RAT; RHINOPHARYNGITIS; SINGLE DRUG DOSE; SOMNOLENCE; SPRAGUE DAWLEY RAT; TREATMENT RESISTANT DEPRESSION; TREATMENT RESPONSE; UPPER ABDOMINAL PAIN; URINARY TRACT INFECTION; XEROSTOMIA; ADULT; AGED; ANIMAL; ANTAGONISTS AND INHIBITORS; BRAIN; CLINICAL TRIAL; CROSSOVER PROCEDURE; DEPRESSIVE DISORDER, MAJOR; DEPRESSIVE DISORDER, TREATMENT-RESISTANT; DOUBLE BLIND PROCEDURE; DRUG EFFECTS; FEMALE; METABOLISM; MIDDLE AGED; PATHOPHYSIOLOGY; PHASE 1 CLINICAL TRIAL; PHASE 2 CLINICAL TRIAL; PSYCHOLOGICAL RATING SCALE; RANDOMIZED CONTROLLED TRIAL; TREATMENT OUTCOME; YOUNG ADULT;

ADULT; AGED; ANIMALS; ANTIDEPRESSIVE AGENTS; BRAIN; CROSS-OVER STUDIES; DEPRESSIVE DISORDER, MAJOR; DEPRESSIVE DISORDER, TREATMENT-RESISTANT; DOUBLE-BLIND METHOD; ELECTROENCEPHALOGRAPHY; FEMALE; HUMANS; KETAMINE; MALE; MIDDLE AGED; PHENETHYLAMINES; PSYCHIATRIC STATUS RATING SCALES; PYRIDINES; RATS, SPRAGUE-DAWLEY; RECEPTORS, N-METHYL-D-ASPARTATE; TREATMENT OUTCOME; YOUNG ADULT;

EID: 84908572031     PISSN: 13594184     EISSN: 14765578     Source Type: Journal    
DOI: 10.1038/mp.2013.130     Document Type: Article

References (37)

1. World Health Organization. The Global Burden of Disease: 2004 Update. WHO Press: Geneva, Switzerland, Available at http://www.who.int/healthinfo/global- burden-disease/2004-report-update/en/index.html. Accessed 14 September, 2012.
2. Insel TR, Wang PS. The STAR∗D trial: revealing the need for better treatments. Psychiatr Serv 2009; 60: 1466-1467.
3. Popoli M, Yan Z, McEwen BS, Sanacora G. The stressed synapse: the impact of stress and glucocorticoids on glutamate transmission. Nat Rev Neurosci 2012; 13: 22-37.
4. Sanacora G, Treccani G, Popoli M. Towards a glutamate hypothesis of depression: an emerging frontier of neuropsychopharmacology for mood disorders. Neuropharmacology 2012; 62: 63-77.
5. Sanacora G, Zarate CA, Krystal JH, Manji HK. Targeting the glutamatergic system to develop novel, improved therapeutics for mood disorders. Nat Rev Drug Discov 2008; 7: 426-437.
6. Aan Het RM, Zarate Jr. CA, Charney DS, Mathew SJ. Ketamine for depression: where do we go from here? Biol Psychiatry 2012; 72: 537-547.
7. Krystal JH, Karper LP, Seibyl JP, Freeman GK, Delaney R, Bremner JD et al. Subanesthetic effects of the noncompetitive NMDA antagonist, ketamine, in humans. Psychotomimetic, perceptual, cognitive, and neuroendocrine responses. Arch Gen Psychiatry 1994; 51: 199-214.
8. Maeng S, Zarate Jr. CA, Du J, Schloesser RJ, McCammon J, Chen G et al. Cellular mechanisms underlying the antidepressant effects of ketamine: role of alphaamino- 3-hydroxy-5-methylisoxazole-4-propionic acid receptors. Biol Psychiatry 2008; 63: 349-352.
9. Quirk MC, Sosulski DL, Feierstein CE, Uchida N, Mainen ZF. A defined network of fast-spiking interneurons in orbitofrontal cortex: responses to behavioral contingencies and ketamine administration. Front Syst Neurosci 2009; 3: 13.
10. Homayoun H, Moghaddam B. NMDA receptor hypofunction produces opposite effects on prefrontal cortex interneurons and pyramidal neurons. J Neurosci 2007; 27: 11496-11500.
11. Duman RS, Aghajanian GK. Synaptic dysfunction in depression: potential therapeutic targets. Science 2012; 338: 68-72.
12. Li N, Lee B, Liu RJ, Banasr M, Dwyer JM, Iwata M et al. mTOR-dependent synapse formation underlies the rapid antidepressant effects of NMDA antagonists. Science 2010; 329: 959-964.
13. Coyle JT. The GABA-glutamate connection in schizophrenia: which is the proximate cause? Biochem Pharmacol 2004; 68: 1507-1514.
14. Mealing GA, Lanthorn TH, Murray CL, Small DL, Morley P. Differences in degree of trapping of low-affinity uncompetitive N-methyl-D-aspartic acid receptor antagonists with similar kinetics of block. J Pharmacol Exp Ther 1999; 288: 204-210.
15. Mealing GA, Lanthorn TH, Small DL, Murray RJ, Mattes KC, Comas TM et al. Structural modifications to an N-methyl-D-aspartate receptor antagonist result in large differences in trapping block. J Pharmacol Exp Ther 2001; 297: 906-914.
16. Matejcek M. Cortical correlates of vigilance regulation and their use in evaluating the effects of treatment. Adv Biochem Psychopharmacol 1980; 23: 339-348.
17. Jobert M, Wilson FJ, Ruigt GS, Brunovsky M, Prichep LS, Drinkenburg WH. Guidelines for the recording and evaluation of pharmaco-EEG data in man: the International Pharmaco-EEG Society (IPEG). Neuropsychobiology 2012; 66: 201-220.
18. Rush AJ, Warden D, Wisniewski SR, Fava M, Trivedi MH, Gaynes BN et al. STAR∗D: revising conventional wisdom. CNS Drugs 2009; 23: 627-647.
19. Balestra M, Bernstein P, Ernst GE, Frietze W, McCauley JP, Nugiel D et al. (inventors). AstraZeneca Pharmaceuticals LP (assignee). Ethanamine Compounds and Methods of Using the Same. Patent US20120277272 A1 2012.
20. Dravid SM, Erreger K, Yuan H, Nicholson K, Le P, Lyuboslavsky P et al. Subunitspecific mechanisms and proton sensitivity of NMDA receptor channel block. J Physiol 2007; 581: 107-128.
21. Foster AC, Wong EH. The novel anticonvulsant MK-801 binds to the activated state of the N-methyl-D-aspartate receptor in rat brain. Br J Pharmacol 1987; 91: 403-409.
22. Gilling KE, Jatzke C, Hechenberger M, Parsons CG. Potency, voltage-dependency, agonist concentration-dependency, blocking kinetics and partial untrapping of the uncompetitive N-methyl-D-aspartate (NMDA) channel blocker memantine at human NMDA (GluN1/GluN2A) receptors. Neuropharmacology 2009; 56: 866-875.
23. Hakami T, Jones NC, Tolmacheva EA, Gaudias J, Chaumont J, Salzberg M et al. NMDA receptor hypofunction leads to generalized and persistent aberrant gamma oscillations independent of hyperlocomotion and the state of consciousness. PLoS ONE 2009; 4: e6755.
24. Kocsis B. Differential role of NR2A and NR2B subunits in N-methyl-D-aspartate receptor antagonist-induced aberrant cortical gamma oscillations. Biol Psychiatry 2012; 71: 987-995.
25. Cook IA, Leuchter AF, Morgan M, Witte E, Stubbeman WF, Abrams M et al. Early changes in prefrontal activity characterize clinical responders to antidepressants. Neuropsychopharmacology 2002; 27: 120-131.
26. Horacek J, Brunovsky M, Novak T, Tislerova B, Palenicek T, Bubenikova-Valesova V et al. Subanesthetic dose of ketamine decreases prefrontal theta cordance in healthy volunteers: implications for antidepressant effect. Psychol Med 2010; 40: 1443-1451.
27. Boeijinga PH, Parot P, Soufflet L, Landron F, Danel T, Gendre I et al. Pharmacodynamic effects of acamprosate on markers of cerebral function in alcoholdependent subjects administered as pretreatment and during alcohol abstinence. Neuropsychobiology 2004; 50: 71-77.
28. Palmer GC, Miller JA, Cregan EF, Gendron P, Peeling J. Low-affinity NMDA receptor antagonists. The neuroprotective potential of ARL 15896AR. Ann NY Acad Sci 1997; 825: 220-231.
29. Preskorn SH, Baker B, Kolluri S, Menniti FS, Krams M, Landen JW. An innovative design to establish proof of concept of the antidepressant effects of the NR2B subunit selective N-methyl-D-aspartate antagonist, CP-101,606, in patients with treatment-refractory major depressive disorder. J Clin Psychopharmacol 2008; 28: 631-637.
30. Zarate Jr. CA, Mathews D, Ibrahim L, Chaves JF, Marquardt C, Ukoh I et al. Replication of ketamine's antidepressant efficacy in bipolar depression: a randomized controlled add-on trial. Biol Psychiatry 2012; 71: 939-946.
31. Murrough JW, Perez AM, Pillemer S, Stern J, Parides MK, Aan Het RM et al. Rapid and longer-term antidepressant effects of repeated ketamine infusions in treatment- resistant major depression. Biol Psychiatry 2012; 74: 250-256.
32. Burgdorf J, Zhang XL, Nicholson KL, Balster RL, Leander JD, Stanton PK et al. GLYX-13, a NMDA receptor glycine-site functional partial agonist, induces antidepressant- like effects without ketamine-like side effects. Neuropsychopharmacology 2013; 38: 729-742.
33. Chowdhury GM, Behar KL, Cho W, Thomas MA, Rothman DL, Sanacora G. 1H-[13C]-nuclear magnetic resonance spectroscopy measures of ketamine's effect on amino acid neurotransmitter metabolism. Biol Psychiatry 2012; 71: 1022-1025.
34. Moghaddam B, Adams B, Verma A, Daly D. Activation of glutamatergic neurotransmission by ketamine: a novel step in the pathway from NMDA receptor blockade to dopaminergic and cognitive disruptions associated with the prefrontal cortex. J Neurosci 1997; 17: 2921-2927.
35. Autry AE, Adachi M, Nosyreva E, Na ES, Los MF, Cheng PF et al. NMDA receptor blockade at rest triggers rapid behavioural antidepressant responses. Nature 2011; 475: 91-95.
36. Zarate Jr. CA, Mathews D, Ibrahim L, Chaves JF, Marquardt C, Ukoh I et al. A randomized trial of a low-trapping nonselective N-Methyl-D-Aspartate channel blocker in major depression. Biol Psychiatry 2012; 74: 257-264.
37. Cusin C, Soskin DP, Kara PJ, Kelley D, Trina C, Paolo C et al. Open-label, flexibledose repeated intravenous ketamine infusions as adjunct in outpatients with treatment resistant major depression with suicidal ideation. New Research Approaches for Mental Health Interactions. 28-31 May 2013, Abstract 43.