3- Hydroxy-5-methylisoxazole

AMINESBYREDUCTION] (Vol2) a-Amino-3-hydroxy-5-methylisoxazole-4-propionate... 

Some derivatives of adamantane with antagonist or agonist effects have also been synthesized. For instance, monocationic and dicationic adamantane derivatives block the a-amino-3-hydroxy-5-methylisoxazole -propionic acid (AMPA) receptors, A-methyl-o-aspartate (NMDA) receptors [134—136] and 5-hydroxytryptamine (5-HT3) receptors [137]. 

Zmijewski, M., Gillespie, T.A., Jackson, D.A. etal. (2006) Application of biocatalysis to drug metabolism preparation of mammalian metabolites of a biaryl-bis-sulfonamide AMPA (a-amino-3-hydroxy-5-methylisoxazole-4-propionic acid) receptor potentiator using Actinoplanes missouriensis. Drug Metabolism and Disposition The Biological Fate of Chemicals, 34, 925—931. 

AMPA a-amino-3-hydroxy-5-methylisoxazole-4-propionic acid... 

Four main types of glutamate receptor have been identified and cloned. These are the ionotropic receptors (NMDA and alpha-amino-3-hydroxy-5-methylisoxazole, AMP A, and kainate types) and a group of metabotropic receptors of which eight types have been discovered. The AMP A and kainate receptors are involved in fast excitatory transmission whereas the NMDA receptors mediate slower excitatory responses and play a more complex role in mediating synaptic plasticity. 

The other class is formed by the receptors for glutamate. These are divided on the basis of their activation by specific ligands into NMDA (N-methyl-D-aspartate), kainate and AMPA (a-amino-3-hydroxy-5-methylisoxazole-4-propionic acid) receptors. 

ACPD, fra/7S-l-amino-cyclopentyl-l,3-dicarboxylate AMPA, DL-tt-amino-3-hydroxy-5-methylisoxazole-4-propionate cAMP, cyclic adenosine monophosphate CQNX, 6-cyano-7-nitroquinoxaline-2,3-dione DAG, diacylglycerol IP3, inositol trisphosphate LSD, lysergic acid diethylamide MCPG, a-methyl-4-carboxyphenylglycine. 

Fig. 2.4 Structures of agonists and antagonists of kainate receptors. 5-1 Will, 5-iodowillardiine (a) SYM 2081, (25,4R)-4-methylglutamate (b) 2S,AR isomer of 4-cinnamylglutamic acid (c) AMOA, (RS)-2-amino-3-(3-carboxymethoxy)-5-methylisoxazol-4-yl]propionic acid (d) AMNH, (RS)-2-amino-3-[2-(3-hydroxy-5-methylisoxazol-4-yl)-methyl-5-methyl-3-oxoisoxazo-lin-4-yl)]propionic acid (e) and LY 294486, (3SR,4aRS,6SR,8aRS)-6-[(lH-tetrazol-5-yl)methoxymethyl]-l,2,3,4,4a,5,6,7,8,8a-decahydroisoquinoline-3-carboxylic acid (f)...

Gasull T., DeGregorio-Rocasolano N., and Trullas R. (2001). Overactivation of a-amino-3-hydroxy-5-methylisoxazole-4-propionate and A-mcthyl-D-aspartatc but not kainate receptors inhibits phosphatidylcholine synthesis before excitotoxic neuronal death. J. Neurochem. 77 13-22. 

Shimizu-Sasamata M., Kawasaki-Yatsugi S., Okada M., Sakamoto S., Yatsugi S., Togami J., Hatanaka K., Ohmori J., Koshiya K., Usuda S., and Murase K. (1996). YM90K pharmacological characterization as a selective and potent alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate/kainate receptor antagonist. J. Pharmacol. Exp. Ther. 276 84-92. 

OHDPAT, 8-hydroxy-2(di- -propylamino)tetralin ACPD, trans-1 -amino-cyclopenty 1 -1,3 -dicarboxylate AMP A, DL-cr-amino-3-hydroxy-5-methylisoxazole-4-propionate BIMU8, [endo-A-8-methyl-8-azabicyclo(3.2.1)oct-3-yl]-2,3-dihydro-3-isopropyl-2-oxo-177-benzimidazol-l-carboxamide hydrochloride CGP 35348, 3-aminopropyl(diethoxymethyl)phosphinic acid CNQX, 6-cyano-7-nitroquinoxaline-2,3-dione CP 99994, (+)-(2 , 3A)-3-(2-methoxybenzylamino)-2- ... 

Kurumaji A, Ishimaru M, Torn M. 1992. Alpha-[3H]amino-3-hydroxy-5-methylisoxazole-4-propionic acid binding to human cerebral cortical membranes Minimal changes in postmortem brains of chronic schizophrenics. J Neuro-... 

List of Abbreviations Ach, acetylcholine AMPA, a-amino-3-hydroxy-5-methylisoxazole-4-propionic acid CNS, central nervous system COMT, catechol-O-methyltransferase DA, dopamine DRP-2, dihy-dropyrimidinase-related protein 2 DSM, diagnostic and statistical manual of mental disorders GNAS1, guanine nucleotide-binding protein (G-protein) alpha stimulating activity polypeptide 1 5-HIAA, 5-hydroxyindole acetic acid 5-FIT, serotonin (5-hydroxytryptamine) MAO, monoamine oxidase MHPG, 3-methoxy-4-hydroxyphenylglycol NE, norepinephrine NMDA, N-methyl-D-aspartate PCP, phencyclidine SSRI, selective serotonin reuptake inhibitor SDS, schedule for the deficit syndrome... 

The situation for the 3-substituted compounds resembles that for the 4-substituted isoxazoles. The biologically important 4-aminoalkyl-3-hydroxyisoxazoles (see Section V) exist in the solid phase as zwitterions.288 A recent X-ray crystallographic study of 4-aminomethyl-3-hydroxy-5-methylisoxazole hemihydrate revealed sandwiches of sheets of zwitterions and water molecules held together by hydrogen bonding.277... 

C. Repotentiating a-AMiNO-3-HYDROXY-5-methylisoxazole-4-propionic acid and Kainic Acid Glutamate Receptors... 

Topiramate reduces glutamate release from neurons and antagonizes acdvadon of the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor, a glu-tamatergic excitatory amino acid receptor. A double-blind, placebo-con drolled dial conducted in 296 ALS pa dents over 12 months showed a faster rate of decline in arm sdrength and no effect on survival from topiramate (Cudkowicz et al., 2003). This dial had a large dropout rate and proceeded to a phase HI dial without first exploring the effects of topiramate in the SOD model. 

AID AIDP AIDS AIF AIRE AIS AES AMAN AMN AMPA AMSAN activation-induced (cytidine) deaminase acute inflammatory demyelinating polyradiculoneuropathy acquired immunodeficiency syndrome apoptosis inducing factor autoimmune regulator anterior chamber associated immune deviation (ACAID)-inducing signal amyotrophic lateral sclerosis acute motor axonal neuropathy adrenomyeloneuropathy a-amino-3 -hydroxy-5-methylisoxazole- 4-propionic acid acute motor-sensory axonal neuropathy... 

Lambolez B, Ropert N, Perrais D, Rossier J, Hestrin S (1996) Correlation between kinetics and RNA splicing of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors in neocortical neurons. Proc Natl Acad Sci USA 93 1797-1802. 

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