Systematic (IUPAC) name
(3S,4aR,6R,8aR)-6-[2-(1H-tetrazol-5-yl)ethyl]decahydroisoquinoline-3-carboxylic acid
Clinical data
Legal status
  • Investigational
Routes of
CAS Registry Number  YesY
ATC code None
PubChem CID:
Chemical data
Formula C13H21N5O2
Molecular mass 279.338 g/mol

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]

See also


  1. ^ Gilron I. LY-293558. Eli Lilly & Co. Current Opinion in Investigational Drugs. 2001 Sep;2(9):1273-8. PMID 11717815
  2. ^ Ornstein PL, Arnold MB, Augenstein NK, Lodge D, Leander JD, Schoepp DD. (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. 1993 Jul 9;36(14):2046-8. PMID 8393116
  3. ^ Schoepp DD, Lodge D, Bleakman D, Leander JD, Tizzano JP, Wright RA, Palmer AJ, Salhoff CR, Ornstein PL. 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. 1995 Sep;34(9):1159-68. PMID 8532186
  4. ^ Bleakman R, Schoepp DD, Ballyk B, Bufton H, Sharpe EF, Thomas K, Ornstein PL, Kamboj RK. 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. 1996 Apr;49(4):581-5. PMID 8609884
  5. ^ Li H, Rogawski MA. GluR5 kainate receptor mediated synaptic transmission in rat basolateral amygdala in vitro. Neuropharmacology. 1998Oct-Nov;37(10-11):1279-86. PubMed PMID 9849665.
  6. ^ Bullock R, Graham DI, Swanson S, McCulloch J. Neuroprotective effect of the AMPA receptor antagonist LY-293558 in focal cerebral ischemia in the cat. Journal of Cerebral Blood Flow and Metabolism. 1994 May;14(3):466-71. PMID 8163588
  7. ^ Rogawski MA, Kurzman PS, Yamaguchi SI, Li H. Role of AMPA and GluR5 kainate receptors in the development and expression of amygdala kindling in the mouse. Neuropharmacology. 2001;40(1):28-35. PubMed PMID 11077068.
  8. ^ Liljequist S, Cebers G, Kalda A. 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. 1995 Nov 27;50(11):1761-74. PMID 8615854
  9. ^ Rasmussen K, Kendrick WT, Kogan JH, Aghajanian GK. A selective AMPA antagonist, LY293558, suppresses morphine withdrawal-induced activation of locus coeruleus neurons and behavioral signs of morphine withdrawal. Neuropsychopharmacology. 1996 Nov;15(5):497-505. PMID 8914123
  10. ^ Kest B, McLemore G, Kao B, Inturrisi CE. 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. Journal of Pharmacology and Experimental Therapeutics. 1997 Dec;283(3):1249-55. PMID 9400000
  11. ^ McLemore GL, Kest B, Inturrisi CE. The effects of LY293558, an AMPA receptor antagonist, on acute and chronic morphine dependence. Brain Research. 1997 Dec 5;778(1):120-6. PMID 9462883
  12. ^ Carlezon WA Jr, Rasmussen K, Nestler EJ. AMPA antagonist LY293558 blocks the development, without blocking the expression, of behavioral sensitization to morphine. Synapse. 1999 Mar 15;31(4):256-62. PMID 10051106
  13. ^ Sang CN, Hostetter MP, Gracely RH, Chappell AS, Schoepp DD, Lee G, Whitcup S, Caruso R, Max MB. AMPA/kainate antagonist LY293558 reduces capsaicin-evoked hyperalgesia but not pain in normal skin in humans. Anesthesiology. 1998 Nov;89(5):1060-7. PMID 9821993
  14. ^ Gilron I, Max MB, Lee G, Booher SL, Sang CN, Chappell AS, Dionne RA. 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. 2000 Sep;68(3):320-7. PMID 11014414
  15. ^ Von Bergen NH, Subieta A, Brennan TJ. Effect of intrathecal non-NMDA EAA receptor antagonist LY293558 in rats: a new class of drugs for spinal anesthesia. Anesthesiology. 2002 Jul;97(1):177-82. PMID 12131120
  16. ^ Sang CN, Ramadan NM, Wallihan RG, Chappell AS, Freitag FG, Smith TR, Silberstein SD, Johnson KW, Phebus LA, Bleakman D, Ornstein PL, Arnold B, Tepper SJ, Vandenhende F. LY293558, a novel AMPA/GluR5 antagonist, is efficacious and well-tolerated in acute migraine. Cephalalgia. 2004 Jul;24(7):596-602. PMID 15196302
  17. ^ Lee HJ, Pogatzki-Zahn EM, Brennan TJ. The effect of the AMPA/kainate receptor antagonist LY293558 in a rat model of postoperative pain. Journal of Pain. 2006 Oct;7(10):768-77. PMID 17018337
  18. ^ Jin HC, Keller AJ, Jung JK, Subieta A, Brennan TJ. Epidural tezampanel, an AMPA/kainate receptor antagonist, produces postoperative analgesia in rats. Anesthesia and Analgesia. 2007 Oct;105(4):1152-9. PMID 17898404
  19. ^ Alt A, Weiss B, Ogden AM, Li X, Gleason SD, Calligaro DO, Bleakman D, Witkin JM. 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 (Berlin). 2006 Apr;185(2):240-7. PMID 16470401