Receptor alcohol

Harris RA, Blednov Y, Findlay G et al (2001) Can a single binding site account for actions of alcohols on GABAa and glycine receptors Alcohol Clin Exp Res (5 Suppl) 79S-80S... 

Lovinger DM (2000) Examination of ethanol spermine and acamprosate actions on native and recombinant NMDA receptors. Alcohol Clin Exp Res 24 183A... 

Alcohol acts on the central nervous system in a manner broadly similar to volatile anaesthetics, exerting on cells a generally depressant effect that is probably mediated through particular membrane ion channels and receptors. Alcohol enhances (inhibitory) GABA-stimulated flux of chloride through receptorgated membrane ion channels, a receptor subtype... 

The brain responds to constant dopamine stimulation by down-regulating, or decreasing, the number of D2 dopamine receptors. Alcoholics then drink more and more to try to override this blunted pleasure response. And people with initially low levels of these dopamine receptors are particularly prone to abuse alcohol or other drugs. 

Diphenoxylate Hydrochloride. l-(3-Cyano-3,3-diphenylpropyl)-4-phenyl-4-piperidinecarboxyhc acidmonohydrochlorhydrate [3810-80-8] (Lomotil) (13) is a white, odorless, crystalline powder that melts at 220—226°C. It is soluble ia methanol, spariagly soluble ia ethanol and acetone, slightly soluble ia water and isopropyl alcohol, freely soluble ia chloroform, and practically iasoluble ia ether and hexane. The method of preparation for diphenoxylate hydrochloride is available (11). Diphenoxylate hydrochloride [3810-80-8] (13) is an antidiarrheal that acts through an opiate receptor. It has effects both on propulsive motility and intestinal secretion. Commercial forms are mixed with atropiae to discourage abuse. 

Polymer Applications. The reaction of sahcylaldehyde with poly(vinyl alcohol) to form an acetal has been used to provide dye receptor sites on poly(vinyl alcohol) fibers (89) and to improve the light stabihty of blend fibers from vinyl chloride resin and poly(vinyl alcohol) (90) (see Fibers, POLY(VINYL alcohol)). ... 

Acetylcholine. Acetylcholiae (ACh) (1) is a crystalliae material that is very soluble ia water and alcohol. ACh, synthesized by the enzyme choline acetyltransferase (3), iateracts with two main classes of receptor ia mammals muscarinic (mAChR), defiaed oa the basis of the agonist activity of the alkaloid muscarine (4), and nicotinic (nAChR), based on the agonist activity of nicotine (5) (Table 1). m AChRs are GPCRs (21) n AChRs are LGICs (22). 

The introduction of tritium into molecules is most commonly achieved by reductive methods, including catalytic reduction by tritium gas, PH2], of olefins, catalytic reductive replacement of halogen (Cl, Br, or I) by H2, and metal pH] hydride reduction of carbonyl compounds, eg, ketones (qv) and some esters, to tritium-labeled alcohols (5). The use of tritium-labeled building blocks, eg, pH] methyl iodide and pH]-acetic anhydride, is an alternative route to the preparation of high specific activity, tritium-labeled compounds. The use of these techniques for the synthesis of radiolabeled receptor ligands, ie, dmgs and dmg analogues, has been described ia detail ia the Hterature (6,7). 

The partially alkoxylated chlorotitanates, (RO) TiCl, can be prepared in high purity by reaction of TiCl with an organosilane ester, Si(OR)4 (see Silicon compounds). The degree of esterification of the titanium can be controlled by the amount of silane ester used. When is 3 or 4, the addition of the appropriate alcohol and an amine receptor is required (5). 

The oxidation of a hydroxyl group by an aluminum alkoxide-catalyzed hydrogen exchange with a receptor carbonyl compound is known as the Oppenauer oxidation. For oxidation of steroidal alcohols the reaction is generally... 

Sanofi-Synthelabo researchers discovered pyrazole 53 and analogs to have potent Cannabinoid receptor-1 (CB-1) antagonist/inverse agonist activity and have progressed 53 into development for treatment of obesity and alcohol dependence. The synthesis of 53 was accomplished by heating the diketone sodium salt 51 with the aryl hydrazine hydrochloride in acetic acid to provide the intermediate 52, which was further derivatized... 

The hand-in-glove fit of a chiral substrate into a chiral receptor is relatively straightforward, but it s less obvious how a prochiral substrate can undergo a selective reaction. Take the reaction of ethanol with NAD+ catalyzed by yeast alcohol dehydrogenase. As we saw at the end of Section 9.13, the reaction occurs with exclusive removal of the pro-R hydrogen from ethanol and with addition only to the Re face of the NAD+ carbon. 

Apart from these two Vertex compounds, only one other caspase inhibitor, BDN-6556, has been used in clinical trials. This compound belongs to the class of oxamyl dipeptides and was originally developed by Idun Pharmaceuticals (taken over by Pfizer). It is the only pan-caspase inhibitor that has been evaluated in humans. BDN-6556 displays inhibitory activity against all tested human caspases. It is also an irreversible, caspase-specific inhibitor that does not inhibit other major classes of proteases, or other enzymes or receptors. The therapeutic potential of BDN-6556 was first evaluated in several animal models of liver disease because numerous publications suggested that apoptosis contributes substantially to the development of some hepatic diseases, such as alcoholic hepatitis, hepatitis B and C (HBV, HCV), non-alcoholic steato-hepatitis (NASH), and ischemia/reperfusion injury associated with liver transplant. Accordingly, BDN-6556 was tested in a phase I study. The drug was safe and... 

These findings were unexpected because previous studies had demonstrated that the y2 subunit is required for potentiation of GABAa receptor function by low concentrations of ethanol [2]. The y2 subunit gene is located within a definitely mapped quantitative trait locus (QTL) for acute alcohol withdrawal on mouse chromosome 11 [1]. Allelic variation was genetically... 

Ferreira VM, Frausto S, Browning MD et al (2001) Ionotropic glutamate receptor subunit expression in the rat hippocampus lack of an effect of a long-term ethanol exposure paradigm. Alcohol Clin Exp Res 25 1536-1541... 

Mihic SJ, Ye Q, Wick MJ et al (1997) Sites of alcohol and volatile anaesthetic action on GABAAand glycine receptors. Nature 389 385-389... 

Glycine receptor function is modulated by alcohols and anesthetics [4]. Amino acid residue al(S267) is critical for alcohol potentiation, as mutation to small residues (Gly, Ala) enhance, and mutation to large residues (His, Cys, Tyr) diminish the ethanol effect. Glycine recqrtor modulation by Zn2+ involves structural determinants located within the large N-terminal domain. Additional glycinergic modulators include neuroactive steroids and the anthelmintic, ivermectin, which activates glycine receptors by a novel, strychnine-insensitive mechanism. 

Disorders of lipoprotein metabolism involve perturbations which cause elevation of triglycerides and/or cholesterol, reduction of HDL-C, or alteration of properties of lipoproteins, such as their size or composition. These perturbations can be genetic (primary) or occur as a result of other diseases, conditions, or drugs (secondary). Some of the most important secondary disorders include hypothyroidism, diabetes mellitus, renal disease, and alcohol use. Hypothyroidism causes elevated LDL-C levels due primarily to downregulation of the LDL receptor. Insulin-resistance and type 2 diabetes mellitus result in impaired capacity to catabolize chylomicrons and VLDL, as well as excess hepatic triglyceride and VLDL production. Chronic kidney disease, including but not limited to end-stage... 

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