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Clinical Trials with Drugs Targeting Ionic Channels, Antiporters, and Pumps in Ischemic Stroke

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New Strategies in Stroke Intervention

Part of the book series: Contemporary Neuroscience ((CNEURO))

Abstract

Despite the great concerted efforts to develop effective therapies for brain ischemia, the only successfully available therapy for acute stroke treatment is the recombinant tissue plasminogen activator (rt-PA).

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References

  1. Albers GW, Atkinson RP, Kelley RE, and Rosenbaum DM. Safety, tolerability, and pharmacokinetics of the N-methyl-D-aspartate antagonist dextrorphan in patients with acute stroke. Dextrorphan Study Group. Stroke 26: 254–258, 1995.

    PubMed  CAS  Google Scholar 

  2. Albers GW, Clark WM, Atkinson RP, Madden K, Data JL, and Whitehouse MJ. Dose escalation study of the NMDA glycine-site antagonist licostinel in acute ischemic stroke. Stroke 30: 508–513, 1999.

    PubMed  CAS  Google Scholar 

  3. Albers GW, Goldstein LB, Hall D, and Lesko LM. Aptiganel Acute Stroke Investigators. Aptiganel hydrochloride in acute ischemic stroke: a randomized controlled trial. J Am Med Assoc 286: 2673–2682, 2001.

    Article  CAS  Google Scholar 

  4. Bogousslavsky J, Regli F, Zumstein V, and Köbberling W. Double-blind study of nimodipine in non-severe stroke. Eur Neurol 30: 23–26, 1990.

    Article  PubMed  CAS  Google Scholar 

  5. Bozik M, Homme Ml, Grotta J, Fisher M, Fayad P, Bogousslavsky J, Brunell R, Fernandes L, Colby S, Noonan T, and Douglass A. Post-011: efficacy and safety of MaxiPostTM in Patients with Acute Stroke. JNS 187: S255, 2001.

    Google Scholar 

  6. Cheng YD, Al-Khoury L, and Zivin JA. Neuroprotection for ischemic stroke: two decades of success and failure. NeuroRx 1: 36–45, 2004.

    Article  PubMed  Google Scholar 

  7. Davis SM, Albers GW, Diener HC, Lees KR, and Norris J. Termination of acute stroke studies involving selfotel treatment. ASSIST Steering Committed. Lancet 349: 32, 1997.

    Article  PubMed  CAS  Google Scholar 

  8. Davis SM, Lees KR, Albers GW, Diener HC, Markabi S, Karlsson G, and Norris J. Selfotel in acute ischemic stroke: possible neurotoxic effects of an NMDA antagonist. Stroke 31: 347–354, 2000.

    PubMed  CAS  Google Scholar 

  9. Diener HC, Cortens M, Ford G, Grotta J, Hacke W, Kaste M, Koudstaal PJ, and Wessel T. Lubeluzole in acute ischemic stroke treatment: A double-blind study with an 8-h inclusion window comparing a 10-mg daily dose of lubeluzole with placebo. Stroke 31: 2543–2551, 2000.

    PubMed  CAS  Google Scholar 

  10. Diener HC, Hacke W, Hennerici M, Radberg J, Hantson L, and De Keyser J. Lubeluzole in acute ischemic stroke. A double-blind, placebo-controlled phase II trial. Lubeluzole International Study Group. Stroke 27: 76–81, 1996.

    PubMed  CAS  Google Scholar 

  11. Diener HC. Multinational randomised controlled trial of lubeluzole in acute ischaemic stroke. European and Australian Lubeluzole Ischaemic Stroke Study Group. Cerebrovasc Dis 8: 172–181, 1998.

    Article  PubMed  CAS  Google Scholar 

  12. Dyker AG and Lees KR. Remacemide hydrochloride: a double-blind, placebo-controlled, safety and tolerability study in patients with acute ischemic stroke. Stroke 30: 1796–1801, 1999.

    PubMed  CAS  Google Scholar 

  13. Dyker AG and Lees KR. Safety and tolerability of GV150526 (a glycine site antagonist at the N-methyl-D-aspartate receptor) in patients with acute stroke. Stroke 30: 986–992, 1999.

    PubMed  CAS  Google Scholar 

  14. Dyker AG, Edwards KR, Fayad PB, Hormes JT, and Lees KR. Safety and tolerability study of aptiganel hydrochloride in patients with an acute ischemic stroke. Stroke 30: 2038–2042, 1999.

    PubMed  CAS  Google Scholar 

  15. Elting JW, Sulter GA, Kaste M, Lees KR, Diener HC, Hommel M, Versavel M, Teelken AW, and De Keyser J. AMPA antagonist ZK200775 in patients with acute ischemic stroke: possible glial cell toxicity detected by monitoring of S-100B serum levels. Stroke 33: 2813–2818, 2002.

    Article  PubMed  CAS  Google Scholar 

  16. Franke CL, Palm R, Dalby M, Schoonderwaldt HC, Hantson L, Eriksson B, Lang-Jenssen L, and Smakman J. Flunarizine in stroke treatment (FIST): a double-blind, placebo-controlled trial in Scandinavia and the Netherlands. Acta Neurol Scand 93: 56–60, 1996.

    Article  PubMed  CAS  Google Scholar 

  17. Gelmers HJ, Gorter K, de Weerdt CJ, and Wiezer HJ. A controlled trial of nimodipine in acute ischemic stroke. N Engl J Med 318: 203–207, 1988.

    Article  PubMed  CAS  Google Scholar 

  18. Gelmers HJ. The effects of nimodipine on the clinical course of patients with acute ischemic stroke. Acta Neurol Scand 69: 232–239, 1984.

    Article  PubMed  CAS  Google Scholar 

  19. Ginsberg MD. Neuroprotection for ischemic stroke: past, present and future. Neuropharmacology 55: 363–389, 2008.

    Article  PubMed  CAS  Google Scholar 

  20. Grotta J, Clark W, Coull B, Pettigrew LC, Mackay B, Goldstein LB, Meissner I, Murphy D, and La Rue L.. Safety and tolerability of the glutamate antagonist CGS 19755 (Selfotel) in patients with acute ischemic stroke. Results of a phase IIa randomized trial. Stroke 26: 602–605, 1995.

    PubMed  CAS  Google Scholar 

  21. Grotta J. Combination Therapy Stroke Trial Investigators. Combination Therapy Stroke Trial: recombinant tissue-type plasminogen activator with/without lubeluzole. Cerebrovasc Dis 12: 258–263, 2001.

    Article  PubMed  CAS  Google Scholar 

  22. Grotta J. Lubeluzole treatment of acute ischemic stroke. The US and Canadian Lubeluzole Ischemic Stroke Study Group. Stroke 28: 2338–2346, 1997.

    PubMed  CAS  Google Scholar 

  23. Heiss WD, Holthoff V, Pawlik G, and Neveling M. Effect of nimodipine on regional cerebral glucose metabolism in patients with acute ischemic stroke as measured by positron emission tomography. J Cereb Blood Flow Metab 10: 127–132, 1990.

    PubMed  CAS  Google Scholar 

  24. Horn J, de Haan RJ, Vermeulen M, and Limburg M. Very Early Nimodipine Use in Stroke (VENUS): a randomized, double-blind, placebo-controlled trial. Stroke 32: 461–465, 2001.

    Article  PubMed  CAS  Google Scholar 

  25. Internet Stroke Center. Stroke Trials Registry. http://www.strokecenter.org/trials/index.aspx, 2009.

  26. Kaste M, Fogelholm R, Erilä T, Palomäki H, Murros K, Rissanen A, and Sarna S. A randomized, double-blind, placebo-controlled trial of nimodipine in acute ischemic hemispheric stroke. Stroke 25: 1348–1353, 1994.

    PubMed  CAS  Google Scholar 

  27. Lees KR, Asplund K, Carolei A, Davis SM, Diener HC, Kaste M, Orgogozo JM, and Whitehead J. Glycine antagonist (gavestinel) in neuroprotection (GAIN International) in patients with acute stroke: a randomised controlled trial. GAIN International Investigators. Lancet 355: 1949–1954, 2000.

    Article  PubMed  CAS  Google Scholar 

  28. Lees KR. Cerestat and other NMDA antagonists in ischemic stroke. Neurology 49: S66–S69, 1997.

    PubMed  CAS  Google Scholar 

  29. Limburg M and Hijdra A. Flunarizine in acute ischemic stroke: a pilot study. Eur Neurol 30: 121–2, 1990.

    Article  PubMed  CAS  Google Scholar 

  30. Lyden P, Jacoby M, Schim J, Albers G, Mazzeo P, Ashwood T, Nordlund A, and Odergren T. The Clomethiazole Acute Stroke Study in tissue-type plasminogen activator-treated stroke (CLASS-T): final results. Neurology 57: 1199–1205, 2001.

    PubMed  CAS  Google Scholar 

  31. Martínez-Vila E, Guillén F, Villanueva JA, Matías-Guiu J, Bigorra J, Gil P, Carbonell A, and Martínez-Lage JM. Placebo-controlled trial of nimodipine in the treatment of acute ischemic cerebral infarction. Stroke 21: 1023–1028, 1990.

    PubMed  Google Scholar 

  32. Morris GF, Bullock R, Marshall SB, Marmarou A, Maas A, and Marshall LF. Failure of the competitive N-methyl-D-aspartate antagonist Selfotel (CGS 19755) in the treatment of severe head injury: results of two phase III clinical trials. The Selfotel Investigators. J Neurosurg 91: 737–743, 1999.

    Article  PubMed  CAS  Google Scholar 

  33. Mueller AL, Artman LD, Balandrin MF, Brady E, Chien Y, DelMar EG, Kiersted A, Marriott TB, Moe ST, Raszkiewicz JL, VanWagenen B, and Wells D. NPS 1506, a moderate affinity uncompetitive NMDA receptor antagonist: preclinical summary and clinical experience. Amino Acids 19: 177–179, 2000.

    Article  PubMed  CAS  Google Scholar 

  34. Muir KW and Lees KR. A randomized, double-blind, placebo-controlled pilot trial of intravenous magnesium sulfate in acute stroke. Stroke 26: 1183–1188, 1995.

    PubMed  CAS  Google Scholar 

  35. Muir KW, Hamilton SJ, Lunnon MW, Hobbiger S, and Lees KR. Safety and tolerability of 619C89 after acute stroke. Cerebrovasc Dis 8: 31–37, 1998.

    Article  PubMed  CAS  Google Scholar 

  36. Muir KW, Holzapfel L, and Lees KR. Phase II clinical trial of sipatrigine (619C89) by continuous infusion in acute stroke. Cerebrovasc Dis 10: 431–436, 2000.

    Article  PubMed  CAS  Google Scholar 

  37. Muir KW, Lees KR, Ford I, and Davis S. Intravenous Magnesium Efficacy in Stroke (IMAGES) Study Investigators. Magnesium for acute stroke (Intravenous Magnesium Efficacy in Stroke trial): randomised controlled trial. Lancet 363: 439–445, 2004.

    Article  PubMed  CAS  Google Scholar 

  38. Nag D, Garg RK, and Varma M. A randomized double-blind controlled study of nimodipine in acute cerebral ischemic stroke. Indian J Physiol Pharmacol 42: 555–558, 1998.

    PubMed  CAS  Google Scholar 

  39. Norris JW, LeBrun LH, and Anderson BA. Intravenous nimodipine in acute ischaemic stroke. Cerebrovasc Dis 4: 194–196, 1994.

    Article  Google Scholar 

  40. O’Collins VE, Macleod MR, Donnan GA, Horky LL, van der Worp BH, and Howells DW. 1,026 experimental treatments in acute stroke. Ann Neurol 59: 467–477, 2006.

    Article  PubMed  Google Scholar 

  41. Paci A, Ottaviano P, Trenta A, Iannone G, De Santis L, Lancia G, Moschini E, Carosi M, Amigoni S, and Caresia L. Nimodipine in acute ischemic stroke: a double-blind controlled study. Acta Neurol Scand 80: 282–286, 1989.

    Article  PubMed  CAS  Google Scholar 

  42. Pulsinelli W, Mann M, Welch M, et al. Fosphenytoin in acute ischemic stroke: efficacy results. Neurology 52: A384, 1999.

    Google Scholar 

  43. Sacco RL, DeRosa JT, Haley EC Jr, Levin B, Ordronneau P, Phillips SJ, Rundek T, Snipes RG, and Thompson JL. Glycine Antagonist in Neuroprotection Americas Investigators. Glycine antagonist in neuroprotection for patients with acute stroke: GAIN Americas: a randomized controlled trial. J Am Med Assoc 285: 1719–1728, 2001.

    Article  CAS  Google Scholar 

  44. Saver JL, Kidwell C, Eckstein M, and Starkman S. FAST-MAG Pilot Trial Investigators. Prehospital neuroprotective therapy for acute stroke: results of the Field Administration of Stroke Therapy-Magnesium (FAST-MAG) pilot trial. Stroke 35: 106–108, 2004.

    Article  Google Scholar 

  45. The American Nimodipine Study Group. Clinical trial of nimodipine in acute ischemic stroke. Stroke 23: 3–8, 1992.

    Google Scholar 

  46. The North American Glycine Antagonist in Neuroprotection (GAIN) Investigators. Phase II studies of the glycine antagonist GV150526 in acute stroke: the North American experience. Stroke 31: 358–365, 2000.

    Google Scholar 

  47. Trust Study Group. Randomised, double-blind, placebo-controlled trial of nimodipine in acute stroke. Lancet 336: 1205–1209, 1990.

    Article  Google Scholar 

  48. Wahlgren NG, MacMahon DG, De Keyser J, Indredavik B, and Ryman T. Intravenous Nimodipine West European Stroke Trial (INWEST) of nimodipine in the treatment of acute ischaemic stroke. Cerebrovasc Dis 4: 204 –210, 1994.

    Article  Google Scholar 

  49. Wahlgren NG, Ranasinha KW, Rosolacci T, Franke CL, van Erven PM, Ashwood T, and Claesson L. Clomethiazole acute stroke study (CLASS): results of a randomized, controlled trial of clomethiazole versus placebo in 1360 acute stroke patients. Stroke 30: 21–28, 1999.

    PubMed  CAS  Google Scholar 

  50. Walters MR, Kaste M, Lees KR, Diener HC, Hommel M, De Keyser J, Steiner H, and Versavel M. The AMPA antagonist ZK 200775 in patients with acute ischaemic stroke: a double-blind, multicentre, placebo-controlled safety and tolerability study. Cerebrovasc Dis 20: 304–309, 2005.

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Lucio Annunziato .

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Spinali, A., Pignataro, G., Di Renzo, G., Annunziato, L. (2009). Clinical Trials with Drugs Targeting Ionic Channels, Antiporters, and Pumps in Ischemic Stroke. In: Annunziato, L. (eds) New Strategies in Stroke Intervention. Contemporary Neuroscience. Humana Press. https://doi.org/10.1007/978-1-60761-280-3_13

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