2-Amino-3- propionic acid AMPA

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]. 

Abbreviations N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA), L(+)-2 amino-3-phosphonopropionic acid (L-AP3), 6-cyano-7-nitroqninoxaline (CNQ5Q, 2,3-dihydroxy-6-nitro-7-sulfamyl-benzo-f-quinoxaline (NBQX), 3-(2-carboxypiperazin-4-yl)-propyl-l-phosphonic acid (CPP), 7 Chlorokynnreic... 

In vitro studies on excitotoxicity suggest that while both NMDA and a-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)/kainate (KA) receptors can mediate excitotoxicity (see Ch. 15), these classes of glutamate receptors do not do so equally. Experiments with cortical or hippocampal cell cultures suggest that much of the neuronal death associated with brief, intense glutamate exposure is mediated by NMDA receptor activation, probably because this can induce lethal amounts of Ca2+ influx more rapidly than can AMPA/KA receptor stimulation. 

Lesions of the basal forebrain cholinergic system using a-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) result in impaired attentional, but not mnemonic, function in rats (Muir et al., 1995) and monkeys (Voytko et al., 1994), an effect which has been confirmed using more selective IgG-saporin lesions (Baxter et al., 1995 Everitt 8c Robbins, 1997). 

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. 

The ionotropic glutamic acid or-amino-B-hydroxy-.S-mcthyl-4-i.soxazolc propionic acid (AMPA) receptors are activate by brain-penetrating ampakines. There are suggestions that thc.se agents exert. some antipsychotic actions by increasing glutaminergic activity. 

Pharmacology and Mechanism of Action. Topiramate is a sulfamate-substituted monosaccharide that has multiple modes of action involving voltage-dependent sodium channels, GABA receptors, and antagonism of a-amino-3-hydroxy-5-methyl-4-isoxazole-4-propionic acid (AMPA) subtype glutamate receptors. ... 

Kunig G, Niedermeyer B, Deckert J et al (1998) Inhibition of [3H]alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid [AMPA] binding by the anticonvulsant valproate in clinically relevant concentrations an autoradiographic investigation in human hippocampus. Epilepsy Res 31 153-157... 

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