Selfotel

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IUPAC_name = (2S,4R)-4-(phosphonomethyl)piperidine-2-carboxylic acid


width = 280
CAS_number = 110347-85-8
synonyms = Selfotel
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PubChem = 68736
DrugBank =
C = 7 | H = 14 | N = 1 | O = 5 | P = 1
molecular_weight = 223.164 g/mol
smiles = C1CN [C@@H] (C [C@@H] 1CP(=O)(O)O)C(=O)O
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legal_status = Legal
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Selfotel (CGS-19755) is a drug which acts as a competitive NMDA antagonist, directly competing with glutamate for binding to the receptor. [Lehmann J, Hutchison AJ, McPherson SE, Mondadori C, Schmutz M, Sinton CM, Tsai C, Murphy DE, Steel DJ, Williams M, et al. CGS 19755, a selective and competitive N-methyl-D-aspartate-type excitatory amino acid receptor antagonist. "Journal of Pharmacology and Experimental Therapeutics". 1988 Jul;246(1):65-75. PMID 2899170] Initial studies showed it to have anticonvulsant, anxiolytic, analgesic and neuroprotective effects, [Bennett DA, Lehmann J, Bernard PS, Liebman JM, Williams M, Wood PL, Boast CA, Hutchison AJ. CGS 19755: a novel competitive N-methyl-D-aspartate (NMDA) receptor antagonist with anticonvulsant, anxiolytic and anti-ischemic properties. "Progress in Clinical and Biological Research". 1990;361:519-24. PMID 1981269] [France CP, Winger GD, Woods JH. Analgesic, anesthetic, and respiratory effects of the competitive N-methyl-D-aspartate (NMDA) antagonist CGS 19755 in rhesus monkeys. "Brain Research". 1990 Sep 3;526(2):355-8. PMID 2257491] and it was originally researched for the treatment of stroke, [Grotta J, Clark W, Coull B, Pettigrew LC, Mackay B, Goldstein LB, Meissner I, Murphy D, LaRue 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". 1995 Apr;26(4):602-5. PMID 7709405] but subsequent animal and human studies showed phencyclidine-like effects, [Bennett DA, Bernard PS, Amrick CL, Wilson DE, Liebman JM, Hutchison AJ. Behavioral pharmacological profile of CGS 19755, a competitive antagonist at N-methyl-D-aspartate receptors. "Journal of Pharmacology and Experimental Therapeutics". 1989 Aug;250(2):454-60. PMID 2547931] [Koek W, Woods JH, Colpaert FC. N-methyl-D-aspartate antagonism and phencyclidine-like activity: a drug discrimination analysis. "Journal of Pharmacology and Experimental Therapeutics". 1990 Jun;253(3):1017-25. PMID 2193142] [Lu Y, France CP, Woods JH. Tolerance to the cataleptic effect of the N-methyl-D-aspartate (NMDA) receptor antagonists in pigeons: cross-tolerance between PCP-like compounds and competitive NMDA antagonists. "Journal of Pharmacology and Experimental Therapeutics". 1992 Nov;263(2):499-504. PMID 1432686] [Baron SP, Woods JH. Competitive and uncompetitive N-methyl-D-aspartate antagonist discriminations in pigeons: CGS 19755 and phencyclidine. "Psychopharmacology (Berlin)". 1995 Mar;118(1):42-51. PMID 7597121] as well as limited efficacy and evidence for possible neurotoxicity under some conditions, [Morris GF, Bullock R, Marshall SB, Marmarou A, Maas A, 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. "Journal of Neurosurgery". 1999 Nov;91(5):737-43. PMID 10541229] [Davis SM, Lees KR, Albers GW, Diener HC, Markabi S, Karlsson G, Norris J. Selfotel in acute ischemic stroke : possible neurotoxic effects of an NMDA antagonist. "Stroke". 2000 Feb;31(2):347-54. PMID 10657404] [Dawson DA, Wadsworth G, Palmer AM. A comparative assessment of the efficacy and side-effect liability of neuroprotective compounds in experimental stroke. "Brain Research". 2001 Feb 23;892(2):344-50. PMID 11172782] and so clinical development was ultimately discontinued. [Ikonomidou C, Turski L. Why did NMDA receptor antagonists fail clinical trials for stroke and traumatic brain injury? "Lancet Neurology". 2002 Oct;1(6):383-6. PMID 12849400] [Farin A, Marshall LF. Lessons from epidemiologic studies in clinical trials of traumatic brain injury. "Acta Neurochirurgica. Supplement". 2004;89:101-7. PMID 15335108]

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