Dose escalation safety and tolerance study of the competitive NMDA antagonist selfotel (CGS 19755) in neurosurgery patients

Clinical Neuropharmacology

Volumn 21, Issue 1, 1998, Pages 28-34

  Yenari, Midori A ^a   Bell, Teresa E ^a   Kotake, Alvin N ^b   Powell, Mark ^b   Steinberg, Gary K ^a  

^a STANFORD UNIVERSITY MEDICAL CENTER   (United States)

^b Department of Novartis ^*  (United States)

Author keywords

Cerebral ischemia clinical trial; CGS 19755; Glutamate; NMDA antagonist; Selfotel

Indexed keywords

4 PHOSPHONOMETHYLPIPECOLIC ACID; ALANINE AMINOTRANSFERASE; ASPARTATE AMINOTRANSFERASE; BILIRUBIN; HALOPERIDOL; LIVER ENZYME;

ADULT; AGITATION; ARTICLE; ATAXIA; BRAIN ISCHEMIA; CLINICAL ARTICLE; CLINICAL TRIAL; DOSE RESPONSE; DREAMING; DRUG BLOOD LEVEL; DRUG CEREBROSPINAL FLUID LEVEL; DRUG SAFETY; DRUG TOLERABILITY; FEMALE; HALLUCINATION; HUMAN; INTRAVENOUS DRUG ADMINISTRATION; MALE; NEUROPROTECTION; NEUROSURGERY; PARANOIA; PRIORITY JOURNAL; TREATMENT OUTCOME; VERTIGO;

ADOLESCENT; ADULT; AGED; AREA UNDER CURVE; DOSE-RESPONSE RELATIONSHIP, DRUG; EXCITATORY AMINO ACID ANTAGONISTS; FEMALE; HUMANS; MALE; MIDDLE AGED; NEUROPROTECTIVE AGENTS; NEUROSURGICAL PROCEDURES; PIPECOLIC ACIDS; RECEPTORS, N-METHYL-D-ASPARTATE; TREATMENT OUTCOME;

EID: 0031936488     PISSN: 03625664     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (36)

1. Lo EH, Steinberg GK, Panahian N, Maidment NT, Newcomb R. Profiles of extracellular amino acid changes in focal cerebral ischaemia: effects of mild hypothermia. Neural Res 1993;15:281-7.
2. Takagi K, Ginsberg MD, Globus MY, et al. Changes in amino acid neurotransmitters and cerebral blood flow in the ischemic penumbral region following middle cerebral artery occlusion in the rat: correlation with histopathology. J Cereb Blood Flow Metab 1993;13:575-85.
3. Choi DW, Maulucci-Gedde M, Kriegstein AR. Glutamate neurotoxicity in cortical cell culture. J Neurosci 1987;7:357-68.
4. Choi DW. Dextrorphan and dextromethorphan attenuate glutamate neurotoxicity. Brain Res 1987;403:333-6.
5. Choi DW, Peters S, Viseskul V. Dextrorphan and levorphanol selectively block N-methyl-D-aspartate receptor - mediated neurotoxicity on cortical neurons. J Pharmacol Exp Ther 1987;242:713-20.
6. George CP, Goldberg MP, Choi DW, Steinberg GK. Dextromethorphan reduces neocortical ischemic neuronal damage in vivo. Brain Res 1988;440:375-9.
7. Goldberg MP, Pham PC, Choi DW. Dextrorphan and dextromethorphan attenuate hypoxic injury in neuronal culture. Neurosci Lett 1987;80:11-5.
8. Prince DA, Feeser HR. Dextromethorphan protects against cerebral infarction in a rat model of hypoxia-ischemia. Neurosci Lett 1988;85:291-6.
9. Steinberg GK, George CP, DeLaPaz R, Shibata DK, Gross T. Dextromethorphan protects against cerebral injury following transient focal ischemia in rabbits. Stroke 1988;19:1112-8.
10. Steinberg GK, Perez-Pinzon MA, Maier CM, et al. CGS 19755 (selfotel): correlation of in vitro neuroprotection, protection against experimental ischemia and CSF levels in cerebrovascular surgery patients. In: Krieglstein J, Oberpichler-Schwenk H, eds. Pharmacology of cerebral ischemia. Stuttgart: Wissenschaftliche Verlagsgesellschaft mbH, 1994:225-232.
11. Steinberg GK, Saleh J, Kunis D. Delayed treatment with dextromethorphan and dextrorphan reduces cerebral damage after transient focal ischemia. Neurosci Lett 1988;89:193-7.
12. Tortella FC, Martin DA, Allot CP, et al. Dextromethorphan attenuates post-ischemic hypoperfusion following incomplete global ischemia in the anesthetized rat. Brain Res 1989;482:179-83.
13. van Rijen PC, Verheul MB, van Echteld CJ, et al. Effects of dextromethorphan on rat brain during ischemia and reperfusion assessed by magnetic resonance spectroscopy. Stroke 1991;22:343-50.
14. Ohno M, Yamamoto T, Ueki S, Watanabe S. Protection by N-methyl-D-aspartate receptor antagonists against impairment of working memory in rats following transient cerebral ischemia. Neurosci Lett 1992;138:1-4.
15. Shuaib A, Ijaz S, Mazagri R, Senthilsevlvan A. CGS-19755 is neuroprotective during repetitive ischemia: this effect is significantly enhanced when combined with hypothermia. Neuroscience 1993;56:915-20.
16. Swan JH, Meldrum BS. Protection by NMDA antagonists against selective cell loss following transient ischemia. J Cereb Blood Flow Metab 1990;10:343-51.
17. Grotta J, Clark W, Coull B, et al. Safety and tolerability of the glutamate antagonist CGS 19755 (selfotrl) in patients with acute ischemic stroke: results of a phase IIa randomized trial. Stroke 1995;26:602-5.
18. Albers GW, Atkinson RP, Kelley RE, Rosenbaum DM (on behalf of the Dextrorphan Study Group). Safety, tolerability, and pharmako- kinetics of the N-methyl-D-aspartate antagonist dextrorphan in patients with acute stroke. Stroke 1995;26:254-258.
19. Albers GW, Saenz RE, Moses J Jr. Tolerability of oral dextromethorphan in patients with a history of brain ischemia. Clin Neuropharmacol 1992;15:509-14.
20. Albers GW, Saenz RE, Moses J Jr. Choi DW. Safety and tolerance of oral dextromethorphan in patients at risk for brain ischemia. Stroke 1991;22:1075-7.
21. Edwards K, the CNS 1102-008 Study Group. Cerestat (aptiganel hydrochloride) in the treatment of acute ischemic stroke: results of a phase II trial. Neurology 1996;46:A424.
22. Grosset DG, Muir KW, Lees KR. Systemic and cerebral hemodynamic responses to the noncompetitive N-methyl-D-aspartate (NMDA) antagonist CNS 1102. J Cardiovasc Pharmacol 1995;25:705-9.
23. Hollander D, Pradas J, Kaplan R, McLeod HL, Evans WE, Munsat TL. High-dose dextromethorphan in amyotrophic lateral sclerosis:phase I safety and pharmacokinetic studies. Ann Neurol 1994;36:920-4.
24. Muir KW, Grosset DG, Gamzu E, Lees KR. Pharmacological effects of the non-competitive NMDA antagonist CNS 1102 in normal volunteers. Br J Clin Pharmacol 1994;38:33-8.
25. Muir KW, Grosset DG, Lees KR. Clinical pharmacology of CNS 1102 in man. Ann N Y Acad Sci 1995;765:336-7.
26. Muir KW, Grosset DG, Lees KR. Clinical pharmacology of CNS 1102 in volunteers. Ann NY Acad Sci 1995;765:279-89.
27. Steinberg GK, Bell TE, Yenari MA. Dose escalation safety and tolerance study of the NMDA antagonist, dextromethorphan, in neurosurgery patients. J Neurosurg 1996;84:860-866.
28. Wagstaff A, Teasdale GM, Clifton G, Stewart L. The cerebral hemodynamic and metabolic effects of the noncompetitive NMDA antagonist CNS 1102 in humans with severe head injury. Ann NY Acad Sci 1995;765:332-3.
29. Walker FO, Hunt VP. An open label trial of dextromethorphan in Huntington's disease. Clin Neuropharmacol 1989;12:322-30.
30. Warach S, Benfield A, Schlaug G, et al. Stroke therapy evaluated by diffusion weighted imaging: a pilot study of the neuroprotective effect of CERESTAT, a noncompetitivc N-methyl-D-aspartate receptor antagonist, in human stroke. Proc Soc Magnetic Resonance 1996;5:90.
31. Steinberg GK, Bell TE, Kotake A. Dose Escalation Safety and Tolerance Study of the NMDA Antagonist CGS-19755 in Neurosurgical Patients. 44th Annual Meeting of the Congress of Neurological Surgeons. Chicago, IL, 1994;44:172.
32. Perez-Pinzon MA, Maier CM, Yoon EJ, Sun GH, Giffard RG, Steinberg GK. Correlation of CGS 19755 neuroprotection against in vitro excitotoxicity and focal cerebral ischemia. J Cereb Blood Flow Metab 1995;15:865-76.
33. Steinberg GK, Kunis D, DeLaPaz R, Poljak A. Neuroprotection following focal cerebral ischacmia with the NMDA antagonist dextromethorphan has a favourable dose response profile. Neurol Res 1993;15:174-80.
34. Muir KW, Lees KR. Clinical experience with excitatory amino acid antagonist drugs. Stroke 1995;26:503-13.
35. Fisher M, for the CNS 1102-003 Investigators. Cerestat™ (CNS 1102) a non-competitive NMDA antagonist, in ischemic stroke patients: dose escalation safety study. Cerebrovasc Dis 1994;4:245.
36. Olney JW, Labruyere J, Price MT. Pathological changes induced in cerebrocortical neurons by pheneyclidine and related drugs. Science 1989;244:1360-2.