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Tezampanel
Clinical data
Routes of
administration		 IV
ATC code
  • none
Legal status
Legal status
  • Investigational
Identifiers
  • (3S,4aR,6R,8aR)-6-[2-(1H-tetrazol-5-yl)ethyl]decahydroisoquinoline-3-carboxylic acid
CAS Number
PubChem CID
IUPHAR/BPS
ChemSpider
UNII
KEGG
ChEMBL
Chemical and physical data
FormulaC13H21N5O2
Molar mass279.344 g·mol−1
3D model ( JSmol)
  • C1C[C@H]2CN[C@@H](C[C@H]2C[C@H]1CCC3=NNN=N3)C(=O)O
  • InChI=1S/C13H21N5O2/c19-13(20)11-6-10-5-8(1-3-9(10)7-14-11)2-4-12-15-17-18-16-12/h8-11,14H,1-7H2,(H,19,20)(H,15,16,17,18)/t8-,9+,10-,11+/m1/s1 ☒N
  • Key:ZXFRFPSZAKNPQQ-YTWAJWBKSA-N ☒N
 ☒NcheckY  (what is this?)   (verify)

Tezampanel ( INN, USAN) (code names LY-293,558, NGX-424) is a drug originally developed by Eli Lilly [1] which acts as a competitive antagonist of the AMPA and kainate subtypes of the ionotropic glutamate receptor family, [2] [3] with selectivity for the GluR5 subtype of the kainate receptor. [4] [5] It has neuroprotective [6] and anticonvulsant properties, [7] the former of which may, at least in part, occur via blockade of calcium uptake into neurons. [8]

Tezampanel has a range of effects which may be useful for medicinal purposes, as well as its applications in scientific research. It suppresses both the withdrawal symptoms from morphine and other opioids, [9] [10] [11] and the development of tolerance, [12] as well as having antihyperalgesic [13] and analgesic effects in its own right. [14] [15] [16] [17] [18] It also has anxiolytic effects in animal studies and has been suggested as a candidate for the treatment of anxiety in humans. [19]

References

  1. ^ Gilron I (September 2001). "LY-293558. Eli Lilly & Co". Current Opinion in Investigational Drugs. 2 (9): 1273–8. PMID  11717815.
  2. ^ Ornstein PL, Arnold MB, Augenstein NK, Lodge D, Leander JD, Schoepp DD (July 1993). "(3SR,4aRS,6RS,8aRS)-6-[2-(1H-tetrazol-5-yl)ethyl]decahydroisoquinoline-3 - carboxylic acid: a structurally novel, systemically active, competitive AMPA receptor antagonist". Journal of Medicinal Chemistry. 36 (14): 2046–8. doi: 10.1021/jm00066a016. PMID  8393116.
  3. ^ Schoepp DD, Lodge D, Bleakman D, Leander JD, Tizzano JP, Wright RA, et al. (September 1995). "In vitro and in vivo antagonism of AMPA receptor activation by (3S, 4aR, 6R, 8aR)-6-[2-(1(2)H-tetrazole-5-yl) ethyl] decahydroisoquinoline-3-carboxylic acid". Neuropharmacology. 34 (9): 1159–68. doi: 10.1016/0028-3908(95)00099-r. PMID  8532186. S2CID  26092003.
  4. ^ Bleakman R, Schoepp DD, Ballyk B, Bufton H, Sharpe EF, Thomas K, et al. (April 1996). "Pharmacological discrimination of GluR5 and GluR6 kainate receptor subtypes by (3S,4aR,6R,8aR)-6-[2-(1(2)H-tetrazole-5-yl)ethyl]decahyd roisdoquinoline-3 carboxylic-acid". Molecular Pharmacology. 49 (4): 581–5. PMID  8609884.
  5. ^ Li H, Rogawski MA (1998). "GluR5 kainate receptor mediated synaptic transmission in rat basolateral amygdala in vitro". Neuropharmacology. 37 (10–11): 1279–86. doi: 10.1016/s0028-3908(98)00109-9. PMID  9849665. S2CID  22283402.
  6. ^ Bullock R, Graham DI, Swanson S, McCulloch J (May 1994). "Neuroprotective effect of the AMPA receptor antagonist LY-293558 in focal cerebral ischemia in the cat". Journal of Cerebral Blood Flow and Metabolism. 14 (3): 466–71. doi: 10.1038/jcbfm.1994.57. PMID  8163588.
  7. ^ Rogawski MA, Kurzman PS, Yamaguchi SI, Li H (2001). "Role of AMPA and GluR5 kainate receptors in the development and expression of amygdala kindling in the mouse". Neuropharmacology. 40 (1): 28–35. doi: 10.1016/s0028-3908(00)00112-x. PMID  11077068. S2CID  1616466.
  8. ^ Liljequist S, Cebers G, Kalda A (November 1995). "Effects of decahydroisoquinoline-3-carboxylic acid monohydrate, a novel AMPA receptor antagonist, on glutamate-induced CA2+ responses and neurotoxicity in rat cortical and cerebellar granule neurons". Biochemical Pharmacology. 50 (11): 1761–74. doi: 10.1016/0006-2952(95)02032-2. PMID  8615854.
  9. ^ Rasmussen K, Kendrick WT, Kogan JH, Aghajanian GK (November 1996). "A selective AMPA antagonist, LY293558, suppresses morphine withdrawal-induced activation of locus coeruleus neurons and behavioral signs of morphine withdrawal". Neuropsychopharmacology. 15 (5): 497–505. doi: 10.1016/S0893-133X(96)00094-2. PMID  8914123.
  10. ^ Kest B, McLemore G, Kao B, Inturrisi CE (December 1997). "The competitive alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate receptor antagonist LY293558 attenuates and reverses analgesic tolerance to morphine but not to delta or kappa opioids". The Journal of Pharmacology and Experimental Therapeutics. 283 (3): 1249–55. PMID  9400000.
  11. ^ McLemore GL, Kest B, Inturrisi CE (December 1997). "The effects of LY293558, an AMPA receptor antagonist, on acute and chronic morphine dependence". Brain Research. 778 (1): 120–6. doi: 10.1016/s0006-8993(97)00985-2. PMID  9462883. S2CID  30430984.
  12. ^ Carlezon WA, Rasmussen K, Nestler EJ (March 1999). "AMPA antagonist LY293558 blocks the development, without blocking the expression, of behavioral sensitization to morphine". Synapse. 31 (4): 256–62. doi: 10.1002/(SICI)1098-2396(19990315)31:4<256::AID-SYN3>3.0.CO;2-E. PMID  10051106. S2CID  30152197.
  13. ^ Sang CN, Hostetter MP, Gracely RH, Chappell AS, Schoepp DD, Lee G, et al. (November 1998). "AMPA/kainate antagonist LY293558 reduces capsaicin-evoked hyperalgesia but not pain in normal skin in humans". Anesthesiology. 89 (5): 1060–7. doi: 10.1097/00000542-199811000-00005. PMID  9821993. S2CID  34676979.
  14. ^ Gilron I, Max MB, Lee G, Booher SL, Sang CN, Chappell AS, Dionne RA (September 2000). "Effects of the 2-amino-3-hydroxy-5-methyl-4-isoxazole-proprionic acid/kainate antagonist LY293558 on spontaneous and evoked postoperative pain". Clinical Pharmacology and Therapeutics. 68 (3): 320–7. doi: 10.1067/mcp.2000.108677. PMID  11014414. S2CID  8816761.
  15. ^ Von Bergen NH, Subieta A, Brennan TJ (July 2002). "Effect of intrathecal non-NMDA EAA receptor antagonist LY293558 in rats: a new class of drugs for spinal anesthesia". Anesthesiology. 97 (1): 177–82. doi: 10.1097/00000542-200207000-00025. PMID  12131120. S2CID  26550939.
  16. ^ Sang CN, Ramadan NM, Wallihan RG, Chappell AS, Freitag FG, Smith TR, et al. (July 2004). "LY293558, a novel AMPA/GluR5 antagonist, is efficacious and well-tolerated in acute migraine". Cephalalgia. 24 (7): 596–602. doi: 10.1111/j.1468-2982.2004.00723.x. PMID  15196302. S2CID  37366020.
  17. ^ Lee HJ, Pogatzki-Zahn EM, Brennan TJ (October 2006). "The effect of the AMPA/kainate receptor antagonist LY293558 in a rat model of postoperative pain". The Journal of Pain. 7 (10): 768–77. doi: 10.1016/j.jpain.2006.03.010. PMID  17018337.
  18. ^ Jin HC, Keller AJ, Jung JK, Subieta A, Brennan TJ (October 2007). "Epidural tezampanel, an AMPA/kainate receptor antagonist, produces postoperative analgesia in rats". Anesthesia and Analgesia. 105 (4): 1152–9, table of contents. doi: 10.1213/01.ane.0000281435.58012.e3. PMID  17898404. S2CID  16239521.
  19. ^ Alt A, Weiss B, Ogden AM, Li X, Gleason SD, Calligaro DO, et al. (April 2006). "In vitro and in vivo studies in rats with LY293558 suggest AMPA/kainate receptor blockade as a novel potential mechanism for the therapeutic treatment of anxiety disorders". Psychopharmacology. 185 (2): 240–7. doi: 10.1007/s00213-005-0292-0. PMID  16470401. S2CID  12559816.
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