テザンパネル

From Wikipedia, the free encyclopedia

その他名称 LY-293,558; LY-293558; LY293558; LY-326,325; LY-326325; LY326325; NGX-424; NGX424

none

治験中

テザンパネル
臨床データ

その他名称	LY-293,558; LY-293558; LY293558; LY-326,325; LY-326325; LY326325; NGX-424; NGX424
投与経路	IV
ATCコード	none
法的地位	治験中
識別子
IUPAC名 (3S,4aR,6R,8aR)-6-[2-(1H-tetrazol-5-yl)ethyl]decahydroisoquinoline-3-carboxylic acid
CAS登録番号	154652-83-2
PubChem CID	127894
IUPHAR/BPS	4245
ChemSpider	113428
UNII	GA36S2O9C2
KEGG	D06656
ChEMBL	ChEMBL14935
化学的および物理的データ
化学式	C₁₃H₂₁N₅O₂
分子量	279.34 g·mol⁻¹
3D model (JSmol)	Interactive image
SMILES C1C[C@H]2CN[C@@H](C[C@H]2C[C@H]1CCC3=NNN=N3)C(=O)O
InChI 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 Key:ZXFRFPSZAKNPQQ-YTWAJWBKSA-N
^N (what is this?) (verify)

テザンパネル（英：Tezampanel (INN, USAN)）、開発コードネームY-293,558、LY-326,325、NGX-424）は、もともとはイーライリリー・アンド・カンパニーが開発した薬物であり^[1]、イオン型グルタミン酸受容体ファミリーにおけるAMPAおよびカイニン酸サブタイプ^[2]^[3]、特にカイニン酸受容体のGluR5サブタイプに対して選択性を示す競合的アンタゴニストとして作用する^[4]^[5]。神経保護作用^[6]と抗てんかん作用^[7]を持ち、前者は少なくとも部分的に、神経細胞へのカルシウム取り込みの遮断を介して生じると考えられる^[8]。

テザンパネルは、科学研究における応用に加え、医療目的にも有用な幅広い効果を持っている。モルヒネやその他のオピオイドによる離脱症状^[9]^[10]^[11]と耐性の発現^[12]を抑制するほか、それ自体が抗痛覚過敏作用^[13]と鎮痛作用を持つ^[14]^[15]^[16]^[17]^[18]。動物実験では抗不安作用も持ち、ヒトにおける不安の治療のための候補として提案されている^[19]。

テザンパネルの遊離塩基はLY-293558として知られているのに対し、テザンパネルの塩酸塩はLY-326325として知られているとされる^[20]^[21]。

↑ “LY-293558. Eli Lilly & Co”. Current Opinion in Investigational Drugs 2 (9): 1273–8. (September 2001). PMID 11717815.
↑ “(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. (July 1993). doi:10.1021/jm00066a016. PMID 8393116.
↑ “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. (September 1995). doi:10.1016/0028-3908(95)00099-r. PMID 8532186.
↑ “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. (April 1996). doi:10.1016/S0026-895X(25)08763-2. PMID 8609884.
↑ “GluR5 kainate receptor mediated synaptic transmission in rat basolateral amygdala in vitro”. Neuropharmacology 37 (10–11): 1279–86. (1998). doi:10.1016/s0028-3908(98)00109-9. PMID 9849665.
↑ “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. (May 1994). doi:10.1038/jcbfm.1994.57. PMID 8163588.
↑ “Role of AMPA and GluR5 kainate receptors in the development and expression of amygdala kindling in the mouse”. Neuropharmacology 40 (1): 28–35. (2001). doi:10.1016/s0028-3908(00)00112-x. PMID 11077068.
↑ “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. (November 1995). doi:10.1016/0006-2952(95)02032-2. PMID 8615854.
↑ “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. (November 1996). doi:10.1016/S0893-133X(96)00094-2. PMID 8914123.
↑ “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. (December 1997). doi:10.1016/S0022-3565(24)37114-9. PMID 9400000.
↑ “The effects of LY293558, an AMPA receptor antagonist, on acute and chronic morphine dependence”. Brain Research 778 (1): 120–6. (December 1997). doi:10.1016/s0006-8993(97)00985-2. PMID 9462883.
↑ “AMPA antagonist LY293558 blocks the development, without blocking the expression, of behavioral sensitization to morphine”. Synapse 31 (4): 256–62. (March 1999). doi:10.1002/(SICI)1098-2396(19990315)31:4<256::AID-SYN3>3.0.CO;2-E. PMID 10051106.
↑ “AMPA/kainate antagonist LY293558 reduces capsaicin-evoked hyperalgesia but not pain in normal skin in humans”. Anesthesiology 89 (5): 1060–7. (November 1998). doi:10.1097/00000542-199811000-00005. PMID 9821993.
↑ “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. (September 2000). doi:10.1067/mcp.2000.108677. PMID 11014414.
↑ “Effect of intrathecal non-NMDA EAA receptor antagonist LY293558 in rats: a new class of drugs for spinal anesthesia”. Anesthesiology 97 (1): 177–82. (July 2002). doi:10.1097/00000542-200207000-00025. PMID 12131120.
↑ “LY293558, a novel AMPA/GluR5 antagonist, is efficacious and well-tolerated in acute migraine”. Cephalalgia 24 (7): 596–602. (July 2004). doi:10.1111/j.1468-2982.2004.00723.x. PMID 15196302.
↑ “The effect of the AMPA/kainate receptor antagonist LY293558 in a rat model of postoperative pain”. The Journal of Pain 7 (10): 768–77. (October 2006). doi:10.1016/j.jpain.2006.03.010. PMID 17018337.
↑ “Epidural tezampanel, an AMPA/kainate receptor antagonist, produces postoperative analgesia in rats”. Anesthesia and Analgesia 105 (4): 1152–9, table of contents. (October 2007). doi:10.1213/01.ane.0000281435.58012.e3. PMID 17898404.
↑ “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. (April 2006). doi:10.1007/s00213-005-0292-0. PMID 16470401.
↑ “Medicinal chemistry of competitive kainate receptor antagonists”. ACS Chem Neurosci 2 (2): 60–74. (February 2011). doi:10.1021/cn1001039. PMC 3369727. PMID 22778857.
↑ “Kainate receptor agonists, antagonists and allosteric modulators”. Curr Pharm Des 8 (10): 873–85. (2002). doi:10.2174/1381612024607108. PMID 11945137.

テザンパネル

Related Articles

Timelines

Top Qs

Fact Checks