Lubeluzole (Prosynap) is a drug which acts as an indirect NMDA antagonist. It inhibits the release of glutamate, inhibits nitric oxide synthesis, and blocks calcium and sodium gated ion channels.[1] It has neuroprotective effects particularly in hypoxic conditions,[2][3] and was developed for the treatment of stroke.[4] Trials showed it to be safe, effective and well tolerated at low doses, but unfortunately higher doses produced the dangerous cardiac side effect of lengthening the QTc interval,[5][6] which could potentially lead to heart failure, and so this meant that subsequent trials were limited to using only the low dose range.[7] Animal studies had shown lubeluzole to produce neuroprotective effects when administered for prolonged periods, but the aim of its developers was to produce a drug that would be effective for preventing damage from acute stroke, and so ultimately it failed to show sufficient efficacy in trials and development for medical use was halted.[8]
^Culmsee C, Junker V, Wolz P, Semkova I, Krieglstein J (January 1998). "Lubeluzole protects hippocampal neurons from excitotoxicity in vitro and reduces brain damage caused by ischemia". European Journal of Pharmacology. 342 (2–3): 193–201. doi:10.1016/s0014-2999(97)01499-4. PMID 9548385.
^Ashton D, Willems R, Wynants J, Van Reempts J, Marrannes R, Clincke G (January 1997). "Altered Na(+)-channel function as an in vitro model of the ischemic penumbra: action of lubeluzole and other neuroprotective drugs". Brain Research. 745 (1–2): 210–21. doi:10.1016/s0006-8993(96)01094-3. PMID 9037412. S2CID 27971291.
^Maiese K, TenBroeke M, Kue I (February 1997). "Neuroprotection of lubeluzole is mediated through the signal transduction pathways of nitric oxide". Journal of Neurochemistry. 68 (2): 710–4. doi:10.1046/j.1471-4159.1997.68020710.x. PMID 9003060. S2CID 15532366.
^Grotta J (December 1997). "Lubeluzole treatment of acute ischemic stroke. The US and Canadian Lubeluzole Ischemic Stroke Study Group". Stroke. 28 (12): 2338–46. doi:10.1161/01.str.28.12.2338. PMID 9412611.
^Hantson L, Tritsmans L, Crabbé R, Gheuens J, Van Rooy P (November 1997). "The safety and tolerability of single intravenous doses of lubeluzole (Prosynap) in healthy volunteers". International Journal of Clinical Pharmacology and Therapeutics. 35 (11): 491–5. PMID 9401829.
^Wood PL, Hawkinson JE (April 1997). "N-methyl-D-aspartate antagonists for stroke and head trauma". Expert Opinion on Investigational Drugs. 6 (4): 389–97. doi:10.1517/13543784.6.4.389. PMID 15989606.
^Hacke W, Lees KR, Timmerhuis T, Haan J, Hantson L, Hennerici M, Diener HC (1998). "Cardiovascular safety of lubeluzole (Prosynap(R)) in patients with ischemic stroke". Cerebrovascular Diseases. 8 (5): 247–54. doi:10.1159/000015861. PMID 9712921. S2CID 25262626.
^Gandolfo C, Sandercock P, Conti M (2002). "Lubeluzole for acute ischaemic stroke". The Cochrane Database of Systematic Reviews (1): CD001924. doi:10.1002/14651858.CD001924. PMID 11869612.
January 29, 2024
lubeluzole, prosynap, drug, which, acts, indirect, nmda, antagonist, inhibits, release, glutamate, inhibits, nitric, oxide, synthesis, blocks, calcium, sodium, gated, channels, neuroprotective, effects, particularly, hypoxic, conditions, developed, treatment, . Lubeluzole Prosynap is a drug which acts as an indirect NMDA antagonist It inhibits the release of glutamate inhibits nitric oxide synthesis and blocks calcium and sodium gated ion channels 1 It has neuroprotective effects particularly in hypoxic conditions 2 3 and was developed for the treatment of stroke 4 Trials showed it to be safe effective and well tolerated at low doses but unfortunately higher doses produced the dangerous cardiac side effect of lengthening the QTc interval 5 6 which could potentially lead to heart failure and so this meant that subsequent trials were limited to using only the low dose range 7 Animal studies had shown lubeluzole to produce neuroprotective effects when administered for prolonged periods but the aim of its developers was to produce a drug that would be effective for preventing damage from acute stroke and so ultimately it failed to show sufficient efficacy in trials and development for medical use was halted 8 LubeluzoleClinical dataATC codenoneIdentifiersIUPAC name 2S 1 4 1 3 benzothiazol 2 yl methylamino piperidin 1 yl 3 3 4 difluorophenoxy propan 2 olCAS Number144665 07 6 YPubChem CID65998ChemSpider59390 NUNIIV2SIB71583KEGGD04789 YChEMBLChEMBL281724 NCompTox Dashboard EPA DTXSID60162779ECHA InfoCard100 233 379Chemical and physical dataFormulaC 22H 25F 2N 3O 2SMolar mass433 52 g mol 13D model JSmol Interactive imageSMILES CN C1CCN CC1 C C H COC2 CC C C C2 F F O C3 NC4 CC CC C4S3InChI InChI 1S C22H25F2N3O2S c1 26 22 25 20 4 2 3 5 21 20 30 22 15 8 10 27 11 9 15 13 16 28 14 29 17 6 7 18 23 19 24 12 17 h2 7 12 15 16 28H 8 11 13 14H2 1H3 t16 m0 s1 NKey OZFSWVOEXHGDES INIZCTEOSA N N N Y what is this verify References edit Culmsee C Junker V Wolz P Semkova I Krieglstein J January 1998 Lubeluzole protects hippocampal neurons from excitotoxicity in vitro and reduces brain damage caused by ischemia European Journal of Pharmacology 342 2 3 193 201 doi 10 1016 s0014 2999 97 01499 4 PMID 9548385 Ashton D Willems R Wynants J Van Reempts J Marrannes R Clincke G January 1997 Altered Na channel function as an in vitro model of the ischemic penumbra action of lubeluzole and other neuroprotective drugs Brain Research 745 1 2 210 21 doi 10 1016 s0006 8993 96 01094 3 PMID 9037412 S2CID 27971291 Maiese K TenBroeke M Kue I February 1997 Neuroprotection of lubeluzole is mediated through the signal transduction pathways of nitric oxide Journal of Neurochemistry 68 2 710 4 doi 10 1046 j 1471 4159 1997 68020710 x PMID 9003060 S2CID 15532366 Grotta J December 1997 Lubeluzole treatment of acute ischemic stroke The US and Canadian Lubeluzole Ischemic Stroke Study Group Stroke 28 12 2338 46 doi 10 1161 01 str 28 12 2338 PMID 9412611 Hantson L Tritsmans L Crabbe R Gheuens J Van Rooy P November 1997 The safety and tolerability of single intravenous doses of lubeluzole Prosynap in healthy volunteers International Journal of Clinical Pharmacology and Therapeutics 35 11 491 5 PMID 9401829 Wood PL Hawkinson JE April 1997 N methyl D aspartate antagonists for stroke and head trauma Expert Opinion on Investigational Drugs 6 4 389 97 doi 10 1517 13543784 6 4 389 PMID 15989606 Hacke W Lees KR Timmerhuis T Haan J Hantson L Hennerici M Diener HC 1998 Cardiovascular safety of lubeluzole Prosynap R in patients with ischemic stroke Cerebrovascular Diseases 8 5 247 54 doi 10 1159 000015861 PMID 9712921 S2CID 25262626 Gandolfo C Sandercock P Conti M 2002 Lubeluzole for acute ischaemic stroke The Cochrane Database of Systematic Reviews 1 CD001924 doi 10 1002 14651858 CD001924 PMID 11869612 Retrieved from https en wikipedia org w index php title Lubeluzole amp oldid 1084243048, wikipedia, wiki, book, books, library,
