Dose escalating safety study of CNS 5161 HCl, a new neuronal glutamate receptor antagonist (NMDA) for the treatment of neuropathic pain

British Journal of Clinical Pharmacology

Volumn 64, Issue 1, 2007, Pages 75-82

  Forst, Thomas ^a,b   Smith, Terry ^c   Schütte, Klemens ^d   Marcus, Paul ^e   Pfützner, Andreas ^b  

^a Department of Internal Medicine   (Germany)

^b JOHANNES GUTENBERG UNIVERSITY   (Germany)

^c CeNeS Ltd   (United Kingdom)

^d Ergomed   (Germany)

^e Marcus Ridley Associates Ltd   (United Kingdom)

Author keywords

Analgesic therapy; NMDA receptor antagonist; Painful neuropathy

Indexed keywords

CNS 5161; N METHYL DEXTRO ASPARTIC ACID RECEPTOR BLOCKING AGENT; PLACEBO; UNCLASSIFIED DRUG;

ABDOMINAL DISCOMFORT; ADULT; AGED; ANALGESIA; ARTICLE; BLOOD PRESSURE; BLURRED VISION; CLINICAL ARTICLE; CLINICAL TRIAL; CONTINUOUS INFUSION; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; CROSSOVER PROCEDURE; DIASTOLIC BLOOD PRESSURE; DOUBLE BLIND PROCEDURE; DRUG BLOOD LEVEL; DRUG DOSE ESCALATION; DRUG EFFICACY; DRUG INDUCED HEADACHE; DRUG SAFETY; DRUG TOLERABILITY; DYSPEPSIA; ECG ABNORMALITY; ELECTROCARDIOGRAM; FEMALE; FLATULENCE; HEADACHE; HEART RATE; HUMAN; LABORATORY TEST; MALE; MULTICENTER STUDY; NAUSEA; NEUROLOGIC DISEASE; NEUROPATHIC PAIN; ORDINAL VERBAL PAIN SCORE; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; RATING SCALE; SIDE EFFECT; SYSTOLIC BLOOD PRESSURE; VISUAL ANALOG SCALE; VISUAL DISORDER;

ADULT; AGED; CROSS-OVER STUDIES; DOSE-RESPONSE RELATIONSHIP, DRUG; DOUBLE-BLIND METHOD; FEMALE; GUANIDINES; HUMANS; MALE; MIDDLE AGED; NEURALGIA; PAIN MEASUREMENT; RECEPTORS, N-METHYL-D-ASPARTATE; SULFHYDRYL COMPOUNDS;

EID: 34250664524     PISSN: 03065251     EISSN: 13652125     Source Type: Journal    
DOI: 10.1111/j.1365-2125.2007.02880.x     Document Type: Article

References (23)

1. Woolf CJ. Dissecting out mechanisms responsible for peripheral neuropathic pain: implications for diagnosis and therapy. Life Sci 2004 74 : 2605 10.
2. Singleton JR. Evaluation and treatment of painful peripheral polyneuropathy. Semin Neurol 2005 25 : 185 95.
3. Pud D, Eisenberg E, Spitzer A, Adler R, Fried G, Yarnitsky D. The NMDA receptor antagonist amantadine reduces surgical neuropathic pain in cancer patients: a double blind, randomized, placebo controlled trial. Pain 1998 75 : 349 54.
4. Stannard CF, Porter GE. Ketamine hydrochloride in the treatment of phantom limb pain. Pain 1993 54 : 227 30.
5. Backonja M, Arndt G, Gombar KA, Check B, Zimmermann M. Response of chronic neuropathic pain syndromes to ketamine: a preliminary study. Pain 1994 56 : 51 7.
6. Carlsson KC, Hoem NO, Moberg ER, Mathisen LC. Analgesic effect of dextromethorphan in neuropathic pain. Acta Anaesthesiol Scand 2004 48 : 328 36.
7. Amin P, Sturrock ND. A pilot study of the beneficial effects of amantadine in the treatment of painful diabetic peripheral neuropathy. Diabet Med 2003 20 : 114 8.
8. Hu LY, Guo J, Magar SS, Fischer JB, Burke-Howie KJ, Durant GJ. Synthesis and pharmacological evaluation of N-(2,5-disubstituted phenyl)-N-(3-substituted phenyl)-N-methylguanidines as N-methyl-D-aspartate receptor ion-channel blockers. J Med Chem 1997 40 : 4281 9.
9. Walters MR, Bradford AP, Fischer J, Lees KR. Early clinical experience with the novel NMDA receptor antagonist CNS 5161. Br J Clin Pharmacol 2002 53 : 305 11.
10. Scott J, Huskisson EC. Graphic representation of pain. Pain 1976 2 : 175 84.
11. Sriwatanakul K, Kelvie W, Lasagna L, Calimlim JF, Weis OF, Mehta G. Studies with different types of visual analog scales for measurement of pain. Clin Pharmacol Ther 1983 34 : 234 9.
12. Barbano R, Hart-Gouleau S, Pennella-Vaughan J, Dworkin RH. Pharmacotherapy of painful diabetic neuropathy. Curr Pain Headache Report 2003 7 : 169 77.
13. Goldstein DJ, Lu Y, Detke MJ, Lee TC, Iyengar S. Duloxetine vs. placebo in patients with painful diabetic neuropathy. Pain 2005 116 : 109 18.
14. Rosenstock J, Tuchman M, LaMoreaux L, Sharma U. Pregabalin for the treatment of painful diabetic peripheral neuropathy: a double-blind, placebo-controlled trial. Pain 2004 110 : 628 38.
15. Freynhagen R, Strojek K, Griesing T, Whalen E, Balkenohl M. Efficacy of pregabalin in neuropathic pain evaluated in a 12-week, randomised, double-blind, multicentre, placebo-controlled trial of flexible- and fixed-dose regimens. Pain 2005 115 : 254 63.
16. Chizh BA, Headley PM. NMDA antagonists and neuropathic pain - multiple drug targets and multiple uses. Curr Pharm Des 2005 11 : 2977 94.
17. Petrenko AB, Yamakura T, Baba H, Shimoji K. The role of N-methyl-D-aspartate (NMDA) receptors in pain: a review. Anesth Analg 2003 97 : 1108 16.
18. Hocking G, Cousins MJ. Ketamine in chronic pain management: an evidence-based review. Anesth Analg 2003 97 : 1730 9.
19. Parsons CG, Danysz W, Quack G. Glutamate in CNS disorders as a target for drug development: an update. Drug News Perspect 1998 11 : 523 69.
20. Parsons CG, Danysz W, Quack G. Memantine is a clinically well tolerated N-methyl-D-aspartate (NMDA) receptor antagonist - a review of preclinical data. Neuropharmacology 1999 38 : 735 67.
21. Wang WZ, Yuan WJ, Su DF. Blockade of N-methyl-D-aspartate receptors within the rostral ventrolateral medulla antagonizes clonidine-induced cardiovascular effects. Auton Neurosci 2003 109 : 21 8.
22. Sitniewska EM, Wisniewska RJ, Wisniewski K. The role of ionotropic receptors of glutaminic acid in cardiovascular system. A. The influence of ionotropic receptor NMDA agonist - 1R,3R-ACPD and antagonist - DL-AP7 on the systemic pressure in rats. Amino Acids 2003 24 : 397 403.
23. Albers GW, Goldstein LB, Hall D, Lesko LM. Aptiganel hydrochloride in acute ischemic stroke: a randomized controlled trial. JAMA 2001 286 : 2673 82.