Y-aminobutyric acid agonists

Diazepam y-Aminobutyric acid agonist 2-10 mg orally 3-4 times/day... 

An example of a hallucinogen affecting mammalian herbivores is the isox-azole muscimol (fig. 11.13), a mushroom toxin. It is a y-aminobutyric acid agonist in the central nervous system of vertebrates. Muscimol s role in nature... 

Krogsgaard-Larsen, P. (1981) -y-Aminobutyric acid agonists, antagonists, and uptake inhibitors. Design and therapeutic aspects. J. Med. Chem. 24 1377-1383. 

Avermectins and Ivermectin. The avermectias are pentacycHc lactones isolated from fermentation products of Streptomjces avermitilis and ivermectin is a semisynthetic chemical, 22,23-dihydroavermectia (46). Ivermectin is effective in very low doses for the control of red spider mites on deciduous fmits, in baits for the control of imported fire ants, and as a parasiticide for Onchocerca volvulus in humans and for catde gmbs. These insecticides appear to function as agonists for the neuroinhibitory transmitter y-aminobutyric acid (GABA) (see Antiparasitic agents, avermectins). 

False neurotransmitters resulting from increased levels of aromatic amino acids, high levels of y-aminobutyric acid, and endogenous benzodiazepines have also been implicated in HE. These substances bind to both the y-aminobutyric acid and benzodiazepine receptors and act as agonists at the active receptor sites.20... 

A similar pathway involving a microwave-driven molybdenum-catalyzed asymmetric allylic alkylation as the key step was elaborated by Moberg and coworkers for the preparation of the muscle relaxant (R)-baclofen (Scheme 6.52) [108]. The racemic form of baclofen is used as a muscle relaxant (antispasmodic) lipophilic derivative of y-aminobutyric acid (GABA). Pharmacological studies have shown that the (R)-enantiomer is the therapeutically useful agonist of the GABAb receptor. Asymmetric alkylation of the allylic carbonate precursor with dimethyl malonate afforded... 

The aforementioned polymer-supported bis-pyridyl ligand has also been applied in microwave-assisted asymmetric allylic alkylation [140], a key step in the enantio-selective synthesis of (R)-baclofen (Scheme 7.118), as reported by Moberg and coworkers. The ( (-enantiomer is a useful agonist of the GABAb (y-aminobutyric acid) receptor, and the racemic form is used as a muscle relaxant (antispasmodic). Under microwave heating, the enantioselectivity could be improved to 89% when using toluene as solvent (see also Scheme 6.52) [140],... 

There is evidence that y-aminobutyric acid A receptors may be modified during SE and become less responsive to endogenous agonists and antagonists. Two phases of GCSE have been identified. During phase I, each seizure produces marked increases in plasma epinephrine, norepinephrine, and steroid concentrations that may cause hypertension, tachycardia, and cardiac arrhythmias. Muscle contractions and hypoxia can cause acidosis, and hypotension, shock, rhabdomyolysis, secondary hyperkalemia, and acute tubular necrosis may ensue. 

Ebert, B., Thompson, S. A., Suonatsou, K McKeman, R., Krogsgaard-Larsen, R, and Waf-ford, K. A. (1997) Differences in agonist/antagonist binding affinity and receptor transduction using recombinant human y-aminobutyric acid type A receptors. Mol. Pharmacol. 52, 1150-1156. 

The applicability of cinchonan carbamate CSPs for bioanalytical investigations using HPLC-ESI-MS/MS has been demonstrated by Fakt et al. [120]. The goal was the stereoselective bioanalysis of (R)-3-amino-2-fluoropropylphosphinic acid, a y-aminobutyric acid (GABA) receptor agonist, in blood plasma in order to determine whether this active enantiomer is in vivo converted to the 5-enantiomer. In this enantioselective HPLC-MS/MS bioassay, sample preparation consisted of... 

The synthetic utility of this PKR process was exemplified in a formal total synthesis of the y-aminobutyric acid (GABA) receptor agonist (R)-baclofen [215],... 

A series of imidazo[l,5-a]quinoxaline amides, carbamates, and ureas which have high affinity for the y-aminobutyric acid A/benzodiazepine receptor complex was developed. Compounds within this class have varying activities ranging from antagonists to full agonists. However, most analogs were found to be partial agonists as indicated by [ S]TBPS and Cl current ratios. Many of these... 

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