Selfotel
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| Klinički podaci | |
|---|---|
| Drugs.com | Monografija |
| Identifikatori | |
| CAS broj | 110347-85-8  |
| ATC kod | None |
| PubChem | CID 68736 |
| UNII | 4VGJ4A41L2 |
| KEGG | D02410 |
| ChEMBL | CHEMBL39664 |
| Sinonimi | Selfotel |
| Hemijski podaci | |
| Formula | C7H14NO5P |
| Molarna masa | 223,164 |
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Selfotel (CGS-19755) je lek koji deluje kao kompetitivni NMDA antagonist, koji se direktno nadmeće sa glutamatom za vezivanje za receptor.[1] Inicijalne studije su pokazale da ima antikonvulzivne, anksiolitičke, analgetičke i neuroprotektivne efekte,[2][3] i prvobitno je istraživan za lečenje moždanog udara,[4] ali kasnije studije na životinjama i ljudima pokazale su efekte slične fenciklidinu,[5][6][7][8] kao i ograničenu efikasnost i evidenciju o mogućoj neurotoksičnosti pod nekim uslovima,[9][10][11] te je klinički razvoj na kraju prekinut.[12][13]
Osobine
[уреди | уреди извор]Selfotel je organsko jedinjenje, koje sadrži 7 atoma ugljenika i ima molekulsku masu od 223,164 Da.
| Osobina | Vrednost |
|---|---|
| Broj akceptora vodonika | 6 |
| Broj donora vodonika | 4 |
| Broj rotacionih veza | 3 |
| Particioni koeficijent[14] (ALogP) | -3,5 |
| Rastvorljivost[15] (logS, log(mol/L)) | 0,2 |
| Polarna površina[16] (PSA, Å2) | 116,7 |
Reference
[уреди | уреди извор]- ^ Lehmann J, Hutchison AJ, McPherson SE, Mondadori C, Schmutz M, Sinton CM, et al. (јул 1988). „CGS 19755, a selective and competitive N-methyl-D-aspartate-type excitatory amino acid receptor antagonist”. The Journal of Pharmacology and Experimental Therapeutics. 246 (1): 65—75. PMID 2899170.
- ^ Bennett DA, Lehmann J, Bernard PS, Liebman JM, Williams M, Wood PL, et al. (1990). „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. 361: 519—24. PMID 1981269.
- ^ France CP, Winger GD, Woods JH (септембар 1990). „Analgesic, anesthetic, and respiratory effects of the competitive N-methyl-D-aspartate (NMDA) antagonist CGS 19755 in rhesus monkeys”. Brain Research. 526 (2): 355—8. PMID 2257491. doi:10.1016/0006-8993(90)91247-e. hdl:2027.42/28393
.
- ^ Grotta J, Clark W, Coull B, Pettigrew LC, Mackay B, Goldstein LB, et al. (април 1995). „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 (4): 602—5. PMID 7709405. doi:10.1161/01.str.26.4.602.
- ^ Bennett DA, Bernard PS, Amrick CL, Wilson DE, Liebman JM, Hutchison AJ (август 1989). „Behavioral pharmacological profile of CGS 19755, a competitive antagonist at N-methyl-D-aspartate receptors”. The Journal of Pharmacology and Experimental Therapeutics. 250 (2): 454—60. PMID 2547931.
- ^ Koek W, Woods JH, Colpaert FC (јун 1990). „N-methyl-D-aspartate antagonism and phencyclidine-like activity: a drug discrimination analysis”. The Journal of Pharmacology and Experimental Therapeutics. 253 (3): 1017—25. PMID 2193142.
- ^ Lu Y, France CP, Woods JH (новембар 1992). „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”. The Journal of Pharmacology and Experimental Therapeutics. 263 (2): 499—504. PMID 1432686.
- ^ Baron SP, Woods JH (март 1995). „Competitive and uncompetitive N-methyl-D-aspartate antagonist discriminations in pigeons: CGS 19755 and phencyclidine”. Psychopharmacology. 118 (1): 42—51. PMID 7597121. doi:10.1007/bf02245248. hdl:2027.42/46346
- ^ Morris GF, Bullock R, Marshall SB, Marmarou A, Maas A, Marshall LF (новембар 1999). „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. 91 (5): 737—43. PMID 10541229. doi:10.3171/jns.1999.91.5.0737.
- ^ Davis SM, Lees KR, Albers GW, Diener HC, Markabi S, Karlsson G, Norris J (фебруар 2000). „Selfotel in acute ischemic stroke : possible neurotoxic effects of an NMDA antagonist”. Stroke. 31 (2): 347—54. PMID 10657404. doi:10.1161/01.str.31.2.347
- ^ Dawson DA, Wadsworth G, Palmer AM (фебруар 2001). „A comparative assessment of the efficacy and side-effect liability of neuroprotective compounds in experimental stroke”. Brain Research. 892 (2): 344—50. PMID 11172782. doi:10.1016/s0006-8993(00)03269-8.
- ^ Ikonomidou C, Turski L (октобар 2002). „Why did NMDA receptor antagonists fail clinical trials for stroke and traumatic brain injury?”. The Lancet. Neurology. 1 (6): 383—6. PMID 12849400. doi:10.1016/s1474-4422(02)00164-3.
- ^ Farin A, Marshall LF (2004). „Lessons from epidemiologic studies in clinical trials of traumatic brain injury”. Acta Neurochirurgica. Supplement. 89: 101—7. ISBN 978-3-7091-7206-3. PMID 15335108. doi:10.1007/978-3-7091-0603-7_14.
- ^ Ghose, A.K.; Viswanadhan V.N. & Wendoloski, J.J. (1998). „Prediction of Hydrophobic (Lipophilic) Properties of Small Organic Molecules Using Fragment Methods: An Analysis of AlogP and CLogP Methods”. J. Phys. Chem. A. 102: 3762—3772. doi:10.1021/jp980230o.
- ^ Tetko IV, Tanchuk VY, Kasheva TN, Villa AE (2001). „Estimation of Aqueous Solubility of Chemical Compounds Using E-State Indices”. Chem Inf. Comput. Sci. 41: 1488—1493. PMID 11749573. doi:10.1021/ci000392t.
- ^ Ertl P.; Rohde B.; Selzer P. (2000). „Fast calculation of molecular polar surface area as a sum of fragment based contributions and its application to the prediction of drug transport properties”. J. Med. Chem. 43: 3714—3717. PMID 11020286. doi:10.1021/jm000942e.
Literatura
[уреди | уреди извор]- Hardman JG, Limbird LE, Gilman AG (2001). Goodman & Gilman's The Pharmacological Basis of Therapeutics (10. изд.). New York: McGraw-Hill. ISBN 0071354697. doi:10.1036/0071422803.
- Thomas L. Lemke; David A. Williams, ур. (2007). Foye's Principles of Medicinal Chemistry (6. изд.). Baltimore: Lippincott Willams & Wilkins. ISBN 0781768799.
