Aceclofenac is a non-steroidal anti-inflammatory drug analog of Diclofenac. It is used for the relief of pain and inflammation in rheumatoid arthritis, osteoarthritis and it should not be given to people with porphyria or breast-feeding mothers, and is not recommended for children. It should be avoided near term in a pregnant woman because of the risk of having a patent ductus arteriosus in the neonate. The drug works by inhibiting the action of cyclooxygenase that is involved in the production of prostaglandins which is accountable for pain, inflammation, chemically, is a crystalline powder with a molecular weight of 354.19. It is practically insoluble in water with good permeability and it is metabolized in human hepatocytes and human microsomes to form acetoxyacetic acid as the major metabolite, which is further conjugated. According to the Biopharmaceutical Classification System drug substances are classified to four classes upon their solubility and permeability, aceclofenac falls under the BCS Class II, poorly soluble and highly permeable drug.
Sources British National Formulary 55, March 2008, ISBN 978-0-85369-776-3 p.537
Dimethyl fumarate is the methyl ester of fumaric acid. DMF was initially recognized as a very effective hypoxic cell radiosensitizer, later, DMF combined with three other fumaric acid esters was licensed in Germany as oral therapy for psoriasis. Other diseases, such as necrobiosis lipoidica, granuloma annulare, phase III clinical trials found that DMF successfully reduced relapse rate and increased time to progression of disability in multiple sclerosis. DMF is thought to have immunomodulatory properties without significant immunosuppression, in a non-medical use, DMF was applied as a biocide in furniture or shoes to prevent growths of mold during storage or transport in a humid climate. Dimethyl fumarate was shown to have a significant effect on relapse rate, Dimethyl fumarate was recommended for approval in the European Union as a peroral treatment for MS by EMA on March 21,2013. One serious side effect that has been described is progressive multifocal leukoencephalopathy, Dimethyl fumarate is an ester and an α, β-unsaturated electrophilic compound which can quickly undergo Michael additions with nucleophiles.
Dimethyl fumarate is an effective diene acceptor in the thermal Diels-Alder reaction, due to the geometry of the starting ester, the Diels-Alder product will have a trans configuration. With this reaction, compounds with bicyclo skeletons can be synthesized, e. g. a diester with a skeleton from dimethyl fumarate. The precise mechanism of action of dimethyl fumarate is unknown, the compound activates the nuclear factor -like 2 pathway and has been identified as a nicotinic acid receptor agonist in vitro. Dimethyl fumarate is a lipophilic, highly mobile molecule in human tissue, as a α, β-unsaturated electrophilic compound, dimethyl fumarate is rapidly attacked by the detoxifying agent glutathione in a Michael addition reaction. Dimethyl fumarate is highly reactive, when administered orally, it does not survive long enough to be absorbed into blood without being attacked by GSH, part of it is hydrolyzed by esterases to produce monomethylfumarate, which is more resistant. Dimethyl fumarate has been found to be an allergic sensitizer at very low concentrations, concentrations as low as 1 ppm may produce allergic reactions.
There are only a handful of equally potent sensitizers, in Finland where the chairs were sold from 2006–2007, sixty users were given serious rashes. In the United Kingdom, sofas sold by Argos, Land of Leather, complaints have been made that dates on the sofas were altered and sofas containing the sachets sold. Land of Leather and Walmsley are facing a ₤10 million class action suit over their reaction to the incident, the danger came to public attention when the BBC Watchdog program alerted consumers to the sofas. In the European Union the use of dimethyl fumarate for consumer products has been forbidden since 1998, the ban on dimethyl fumarate as laid down in Decision 2009/251 establishes a maximum concentration of dimethyl fumarate in products of 0.1 ppm. Products containing more than 0.1 ppm dimethyl fumarate shall be withdrawn from the market, fishersci. ca, Dimethyl fumarate Material Safety Data Sheet
25I-NBOMe is a psychedelic drug and derivative of the substituted phenethylamine psychedelic 2C-I. It was discovered in 2003 by chemist Ralf Heim at the Free University of Berlin, the compound was subsequently investigated by a team at Purdue University led by David Nichols. The carbon-11 labelled version of 25I-NBOMe, Cimbi-5, was synthesized and validated as a radiotracer for positron emission tomography in Copenhagen, being the first 5-HT2A receptor full agonist PET radioligand, -CIMBI-5 shows promise as a more functional marker of these receptors, particularly in their high affinity states. Like other 2C-X-NBOMe molecules, 25I-NBOMe is a derivative of the 2C family of phenethylamines described by Alexander Shulgin in his book PiHKAL, specifically, 25I-NBOMe is an N-benzyl derivative of the phenethylamine molecule 2C-I, formed by adding a 2-methoxybenzyl onto the nitrogen of the phenethylamine backbone. This substitution significantly increases the potency of the molecule, 25I-NBOMe can be synthesised from 2C-I and 2-methoxybenzaldehyde, via reductive alkylation.
It can be done stepwise by first making the imine and reducing the formed imine with sodium borohydride, or by direct reaction with sodium triacetoxyborohydride. 25I-NBOMe acts as a potent full agonist for the human 5-HT2A receptor, with a Ki of 0.044 nM. A radiolabelled form of 25I-NBOMe can be used for mapping the distribution of 5-HT2A receptors in the brain, 25I-NBOMe induces a head-twitch response in mice which is blocked completely by a selective 5-HT2A antagonist, suggesting its psychedelic effects are mediated by 5-HT2A. This study suggested that 25I-NBOMe is approximately 14-fold more potent than 2C-I in-vivo, while in-vitro studies showed that N-benzyl derivatives of 2C-I were significantly increased in potency compared to 2C-I, the N-benzyl derivatives of the related compound DOI were inactive. Although 25I-NBOMe was discovered in 2003, it did not emerge as a recreational drug until 2010. In a slang context, the name of the compound is often shortened to 25I or is called N-Bomb, according to a 2014 survey, 25I-NBOMe is the most frequently used of the NBOMe series.
Case reports of 25I-NBOMe intoxication and without confirmation of the drug in the body, are increasing in the medical literature. 25I-NBOMe is widely rumored to be inactive, oral efficacy has not been disproven. Common routes of administration include sublingual and nasal/intranasal, for sublingual and buccal administration, 25I-NBOMe is often applied to sheets of blotter paper of which small portions are held in the mouth to allow absorption through the oral mucosa. There are reports of intravenous injection of 25I-NBOMe solution and smoking the drug in powdered form, due to its potency and much lower cost than so-called classical or traditional psychedelics, 25I-NBOMe blotters are sometimes misrepresented as, or mistaken for LSD blotters. It is dangerous to attempt to differentiate the two using sensory techniques but reagent testing can easily differentiate ergolines from 25I-NBOMe via colour change, small quantities of 25I-NBOMe can provide a large numbers of doses. Vendors may import 25I-NBOMe in bulk and resell individual doses for considerable profit, 25I-NBOMe is potent, being active in sub-milligram doses. A common dose of the salt is 600–1,200 µg
Acadesine is an adenosine regulating agent developed by PeriCor Therapeutics and licensed to Schering-Plough in 2007 for phase III studies. The drug is a potential agent for prevention of reperfusion injury in CABG surgery. Schering began patient enrollment in phase III studies in May 2009, the trial was terminated in late 2010 based on an interim futility analysis. Reaction with alkoxide interestingly converts the nitrile nearest the sugar to an iminoester, hofmann rearrangement in the presence of a bromine and a base converts the iminoester to the corresponding primary amine. Basic hydrolysis converts the nitrile to an amide, affording acadesine. Acadesine acts as an AMP-activated protein kinase agonist and they looked at the administration of GW501516 in combination with acadesine. Given to mice that did not exercise, this combination activated 40% of the genes that were turned on when mice were given GW1516 and this result drew attention to the compound as a possible athletic endurance aid.
The British Medical Journal reported in 2009 that WADA had found evidence that acadesine was used by cyclists in the 2009 Tour de France
Abamectin is a widely used insecticide and anthelmintic. Abamectin is a mixture of avermectins containing more than 80% avermectin B1a and these two components, B1a and B1b have very similar biological and toxicological properties. The avermectins are insecticidal and antihelmintic compounds derived from various laboratory broths fermented by the soil bacterium Streptomyces avermitilis, abamectin is a natural fermentation product of this bacterium. Abamectin is an insecticide as well as an acaricide and a nematicide, abamectin is used to control insect and mite pests of a range of agronomic, fruit and ornamental crops, and it is used by homeowners for control of fire ants. Abamectin is used as a veterinary antihelmintic, resistance to abamectin-based antihelmintics, although a growing problem, is not as common as to other classes of veterinary antihelmintics. The benzoate salt emamectin benzoate is used as an insecticide. Trade names include Abba, Affirm, Agri-Mek, Dynamec, Epi-Mek, Genesis Horse Wormer, Vertimec, CAM-MEK1.
8% EC, crop Protection Database, Learn more about abamectin
Absinthin is a naturally produced triterpene lactone from the plant Artemisia absinthium. It constitutes one of the most bitter chemical agents responsible for Absinthes distinct taste, the compound shows biological activity and has shown promise as an anti-inflammatory agent, and should not to be confused with thujone, a neurotoxin found in Artemisia absinthium. Total synthesis of -Absinthin was conducted in 2004 by Zhang, et al, the final yield reported for the synthesis was 18. 6% over a course of 10 steps originating from Santonin, a commercially available reagent. The full biosynthesis of Absinthin in Artemisia absinthium has not been elucidated, while terpenoids like Absinthin can be said to consist of isoprene units, isoprene by itself is unstable and does not react directly. Rather, the units are transferred and reacted as diphosphates. As the nomenclature for terpenes suggests, the first Absinthin precursor farnesyl diphosphate contains 15 carbons, diphosphate departure generates a carbo-cation within the synthase, which can be attacked by a carbon-carbon double bond at the opposing end of the molecule.
The first stable intermediate in the pathway in Artemisia is likely Germacrene A. From there, hydroxylation occurs, followed by oxidation to an aldehyde followed by further hydroxylation and formation of a carboxyl group. This reduction does not necessarily occur at step, but may occur further downstream, with the carboxyl and hydroxyl group in position, the guaiano-lactone formation via dehydration can occur, as proposed for a general guaianolide pathway. Oxidation of alcohol to aldol, via -germacrene A hydroxylase, Hydroxylation of alcohol to carboxyl group, via Germacrene A hydroxylase. NADPH-mediated hydroxlation of allylic carbon via a postulated hydroxylation to precede lactone ring closure Lactone formation/ring closure Hydroxylation at carbon-carbon tertiary double bond, additional 5-membered ring formation/cyclization Diels-Alder coupling via an unidentified enzyme in Artemisia absinthium
Acesulfame potassium, known as acesulfame K or Ace K, is a calorie-free sugar substitute often marketed under the trade names Sunett and Sweet One. In the European Union, it is known under the E number E950 and it was discovered accidentally in 1967 by German chemist Karl Clauss at Hoechst AG. In chemical structure, acesulfame potassium is the salt of 6-methyl-1,2, 3-oxathiazine-4-one 2. It is a crystalline powder with molecular formula C 4H 4KNO 4S. Acesulfame K is 200 times sweeter than sucrose, as sweet as aspartame, about two-thirds as sweet as saccharin, like saccharin, it has a slightly bitter aftertaste, especially at high concentrations. Kraft Foods patented the use of sodium ferulate to mask acesulfames aftertaste, acesulfame K is often blended with other sweeteners. These blends are reputed to give a more sucrose-like taste whereby each sweetener masks the others aftertaste, acesulfame potassium has a smaller particle size than sucrose, allowing for its mixtures with other sweeteners to be more uniform.
Although acesulfame potassium has a shelf life, it can eventually degrade to acetoacetamide. In carbonated drinks, it is almost always used in conjunction with another sweetener and it is used as a sweetener in protein shakes and pharmaceutical products, especially chewable and liquid medications, where it can make the active ingredients more palatable. The acceptable daily intake of potassium is listed as 15 mg/kg/day. Acesulfame potassium as well as other sugar substituents were intercalated into some layered double hydroxide hosts by ion exchange, characterization tests have shown that there is complete intercalation of the anions into the LDH hosts. In acesulfame K, the absorption at 1290 cm^-1 is found in the product at 1314 cm^-1. Since this absorption corresponds to the S-O double bond, it means that the bonds interact strongly with the metal hydroxide layers thus an orientation of the molecules is possible. Acesulfame potassium is one of the sweeteners that aids patients with type 1 diabetes.
It provides a sweet taste without affecting glycaemic responses and without the high content of caloric sugars. Some studies, discovered that the consumption of non-nutritive sweeteners has led to weight gain thus increasing the risk of type 2 diabetes, through a Maximal Electroshock Seizure test, non-nutritive sweeteners including acesulfame potassium were labeled as anticonvulsants. This means that there is an association between the structure of the receptor that triggers the sweet sensation and the structure of the targets of antiepileptic drugs. It was discovered that these non-nutritive sweeteners’ anticonvulsant activity is caused by modulation of brain mGlu, acesulfame potassium is widely used in the human diet and excreted by the kidneys
A23187 is a mobile ion-carrier that forms stable complexes with divalent cations. A23187 is known as Calcimycin, Calcium Ionophore, Antibiotic A23187 and it is produced at fermentation of Streptomyces chartreusensis. A23187 has antibiotic properties against gram positive bacteria and fungi and it acts as a divalent cation ionophore, allowing these ions to cross cell membranes, which are usually impermeable to them. A23187 is most selective for Mn2+, somewhat less selective for Ca2+ and Mg2+, much less selective for Sr2+, the ionophore is used in laboratories to increase intracellular Ca2+ levels in intact cells. It uncouples oxidative phosphorylation, the process cells use to synthesize Adenosine triphosphate which they use for energy, in addition, A23187 inhibits mitochondrial ATPase activity. A23187 induces apoptosis in cells and prevents it in others. Inex Pharmaceuticals Corporation reported an innovative application of A23187, inex used A23187 as a molecular tool in order to make artificial liposomes loaded with anti-cancer drugs such as Topotecan.
Recommended use is 0.5 microgram/ml twice for 10 min interrupted with fresh media with 30 min incubation, commercially, A23187 is available as free acid, Ca2+ salt, and 4-brominated analog. A23187 from AG Scientific, another vendor A21387 from BIOMOL, a product page Calcimycin from Bioaustralis
Acephate is an organophosphate foliar insecticide of moderate persistence with residual systemic activity of about 10–15 days at the recommended use rate. It is used primarily for control of aphids, including resistant species, in vegetables and it controls leaf miners, caterpillars and thrips in the previously stated crops as well as turf, and forestry. By direct application to mounds, it is effective in destroying imported fire ants, acephate is sold as a soluble powder, as emulsifiable concentrates, as pressurized aerosol, and in tree injection systems and granular formulations. As of 2012, the EPA no longer allows the usage of acephate on green beans grown in the United States and it is considered non-phytotoxic on many crop plants. Acephate and its metabolite, are toxic to Heliothis spp. that are considered resistant to other organophosphate insecticides. Acephate emits toxic fumes of various oxides of phosphorus, symptoms of exposure to acephate include a slight irritation of eyes and skin.
The U. S. annually uses 4–5 million pounds of acephate, even in small quantities, acephate throws off the navigation systems of white-throated sparrows and other songbirds, making them unable to tell north from south. U. S. EPA Office of Pesticide Programs, cooperative Extension Offices of Cornell University, Oregon State University, the University of Idaho, and the University of California at Davis. Institute for Environmental Toxicology, Michigan State University