PF-3845
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PF-3845
PF-3845 is a selective inhibitor of fatty acid amide hydrolase. It results in increased levels of anandamide and results in cannabinoid receptor-based effects. It has anti-inflammatory action in mice colitis models. Antidiarrheal An anti-diarrhoeal drug (or anti-diarrheal drug in American English) is any medication which provides symptomatic relief for diarrhoea. Types * Electrolyte solutions, while not true antidiarrhoeals, are used to replace lost fluids and salts in ac ... and antinociceptive effects were also seen in mouse models of pain. A 2017 study published in the Journal of Psychiatry and Neuroscience found that PF-3845 exerts rapid and long-lasting anti-anxiety effects in mice exposed acutely to stress or chronically to the stress hormone corticosterone. References {{Cannabinoidergics Cannabinoids Experimental drugs Trifluoromethyl compounds ...
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Fatty Acid Amide Hydrolase
Fatty acid amide hydrolase or FAAH (, oleamide hydrolase, anandamide amidohydrolase) is a member of the serine hydrolase family of enzymes. It was first shown to break down anandamide in 1993. In humans, it is encoded by the gene ''FAAH''.; Function FAAH is an integral membrane hydrolase with a single ''N''-terminal transmembrane domain. ''In vitro'', FAAH has esterase and amidase activity. ''In vivo'', FAAH is the principal catabolic enzyme for a class of bioactive lipids called the fatty acid amides (FAAs). Members of the FAAs include: * Anandamide (''N''-arachidonoylethanolamine), an endocannabinoid * 2-arachidonoylglycerol (2-AG), an endocannabinoid. * Other ''N''-acylethanolamines, such as ''N''-oleoylethanolamine and ''N''-palmitoylethanolamine * The sleep-inducing lipid oleamide * The ''N''-acyltaurines, which are agonists of the transient receptor potential (TRP) family of calcium channels. ''FAAH'' knockout mice display highly elevated (>15-fold) levels of ''N'' ...
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Enzyme Inhibitor
An enzyme inhibitor is a molecule that binds to an enzyme and blocks its activity. Enzymes are proteins that speed up chemical reactions necessary for life, in which substrate molecules are converted into products. An enzyme facilitates a specific chemical reaction by binding the substrate to its active site, a specialized area on the enzyme that accelerates the most difficult step of the reaction. An enzyme inhibitor stops ("inhibits") this process, either by binding to the enzyme's active site (thus preventing the substrate itself from binding) or by binding to another site on the enzyme such that the enzyme's catalysis of the reaction is blocked. Enzyme inhibitors may bind reversibly or irreversibly. Irreversible inhibitors form a chemical bond with the enzyme such that the enzyme is inhibited until the chemical bond is broken. By contrast, reversible inhibitors bind non-covalently and may spontaneously leave the enzyme, allowing the enzyme to resume its function. Reve ...
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Anandamide
Anandamide (ANA), also known as ''N''-arachidonoylethanolamine (AEA), is a fatty acid neurotransmitter. Anandamide was the first endocannabinoid to be discovered: it participates in the body's endocannabinoid system by binding to cannabinoid receptors, the same receptors that the psychoactive compound THC in cannabis acts on. Anandamide is found in nearly all tissues in a wide range of animals. Anandamide has also been found in plants, including small amounts in chocolate. The name 'anandamide' is taken from the Sanskrit word '' ananda'', which means "joy, bliss, delight", plus amide. Anandamide is derived from the non-oxidative metabolism of arachidonic acid, an essential omega-6 fatty acid. It is synthesized from ''N''-arachidonoyl phosphatidylethanolamine by multiple pathways. It is degraded primarily by the fatty acid amide hydrolase (FAAH) enzyme, which converts anandamide into ethanolamine and arachidonic acid. As such, inhibitors of FAAH lead to elevated anandamide leve ...
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Cannabinoid
Cannabinoids () are several structural classes of compounds found in the cannabis plant primarily and most animal organisms (although insects lack such receptors) or as synthetic compounds. The most notable cannabinoid is the phytocannabinoid tetrahydrocannabinol (THC) (delta-9-THC), the primary intoxicating compound in cannabis. Cannabidiol (CBD) is a major constituent of temperate Cannabis plants and a minor constituent in tropical varieties. At least 113 distinct phytocannabinoids have been isolated from cannabis, although only four (i.e., THCA, CBDA, CBCA and their common precursor CBGA) have been demonstrated to have a biogenetic origin. It was reported in 2020 that phytocannabinoids can be found in other plants such as rhododendron, licorice and liverwort, and earlier in Echinacea. Phytocannabinoids are multi-ring phenolic compounds structurally related to THC, but endocannabinoids are fatty acid derivatives. Nonclassical synthetic cannabinoids (cannabimimetics) include amin ...
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Receptor (biochemistry)
In biochemistry and pharmacology, receptors are chemical structures, composed of protein, that receive and transduce signals that may be integrated into biological systems. These signals are typically chemical messengers which bind to a receptor and cause some form of cellular/tissue response, e.g. a change in the electrical activity of a cell. There are three main ways the action of the receptor can be classified: relay of signal, amplification, or integration. Relaying sends the signal onward, amplification increases the effect of a single ligand, and integration allows the signal to be incorporated into another biochemical pathway. Receptor proteins can be classified by their location. Transmembrane receptors include ligand-gated ion channels, G protein-coupled receptors, and enzyme-linked hormone receptors. Intracellular receptors are those found inside the cell, and include cytoplasmic receptors and nuclear receptors. A molecule that binds to a receptor is called a ligand ...
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Anti-inflammatory
Anti-inflammatory is the property of a substance or treatment that reduces inflammation or swelling. Anti-inflammatory drugs, also called anti-inflammatories, make up about half of analgesics. These drugs remedy pain by reducing inflammation as opposed to opioids, which affect the central nervous system to block pain signaling to the brain. Nonsteroidal anti-inflammatory drugs Nonsteroidal anti-inflammatory drugs (NSAIDs) alleviate pain by counteracting the cyclooxygenase (COX) enzyme. On its own, COX enzyme synthesizes prostaglandins, creating inflammation. In whole, the NSAIDs prevent the prostaglandins from ever being synthesized, reducing or eliminating the inflammation and resulting pain. Some common examples of NSAIDs are aspirin, ibuprofen, and naproxen. The newer specific COX-inhibitors are not classified together with the traditional NSAIDs, even though they presumably share the same mode of action. On the other hand, there are analgesics that are commonly associat ...
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Mice
A mouse ( : mice) is a small rodent. Characteristically, mice are known to have a pointed snout, small rounded ears, a body-length scaly tail, and a high breeding rate. The best known mouse species is the common house mouse (''Mus musculus''). Mice are also popular as pets. In some places, certain kinds of field mice are locally common. They are known to invade homes for food and shelter. Mice are typically distinguished from rats by their size. Generally, when a muroid rodent is discovered, its common name includes the term ''mouse'' if it is smaller, or ''rat'' if it is larger. The common terms ''rat'' and ''mouse'' are not taxonomically specific. Typical mice are classified in the genus '' Mus'', but the term ''mouse'' is not confined to members of ''Mus'' and can also apply to species from other genera such as the deer mouse, ''Peromyscus''. Domestic mice sold as pets often differ substantially in size from the common house mouse. This is attributable to breeding a ...
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Colitis
Colitis is swelling or inflammation of the large intestine ( colon). Colitis may be acute and self-limited or long-term. It broadly fits into the category of digestive diseases. In a medical context, the label ''colitis'' (without qualification) is used if: * The cause of the inflammation in the colon is undetermined; for example, ''colitis'' may be applied to ''Crohn's disease'' at a time when the diagnosis is unknown, or * The context is clear; for example, an individual with ulcerative colitis is talking about their disease with a physician who knows the diagnosis. Signs and symptoms The signs and symptoms of colitis are quite variable and dependent on the cause of the given colitis and factors that modify its course and severity. Common symptoms of colitis may include: mild to severe abdominal pains and tenderness (depending on the stage of the disease), persistent hemorrhagic diarrhea with pus either present or absent in the stools, fecal incontinence, flatulence, fatigu ...
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Antidiarrheal
An anti-diarrhoeal drug (or anti-diarrheal drug in American English) is any medication which provides symptomatic relief for diarrhoea. Types * Electrolyte solutions, while not true antidiarrhoeals, are used to replace lost fluids and salts in acute cases. * Bulking agents like methylcellulose, guar gum or plant fibre (bran, sterculia, isabgol, etc.) are used for diarrhoea in functional bowel disease and to control ileostomy output. * Absorbents absorb toxic substances that cause infective diarrhoea, methylcellulose is an absorbent. * Anti-inflammatory compounds such as bismuth subsalicylate. * Anticholinergics reduce intestinal movement and are effective against both diarrhoea and accompanying cramping. * Opioids' classical use besides pain relief is as an anti-diarrhoeal drug. Opioids have agonist actions on the intestinal opioid receptors, which when activated cause constipation. Drugs such as morphine or codeine can be used to relieve diarrhoea this way. A notable opioid fo ...
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Antinociceptive
Nociception (also nocioception, from Latin ''nocere'' 'to harm or hurt') is the Somatosensory system, sensory nervous system's process of encoding Noxious stimulus, noxious stimuli. It deals with a series of events and processes required for an organism to receive a painful stimulus, convert it to a molecular signal, and recognize and characterize the signal in order to trigger an appropriate defense response. In nociception, intense chemical (e.g., capsaicin present in Chili pepper or Cayenne pepper), mechanical (e.g., cutting, crushing), or thermal (heat and cold) stimulation of sensory neurons called nociceptors produces a signal that travels along a chain of nerve fibers via the spinal cord to the brain. Nociception triggers a variety of physiological and behavioral responses to protect the organism against an aggression and usually results in a subjective experience, or perception, of pain in Sentience, sentient beings. Detection of noxious stimuli Potentially damaging mecha ...
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Cannabinoids
Cannabinoids () are several structural classes of compounds found in the cannabis plant primarily and most animal organisms (although insects lack such receptors) or as synthetic compounds. The most notable cannabinoid is the phytocannabinoid tetrahydrocannabinol (THC) (delta-9-THC), the primary intoxicating compound in cannabis. Cannabidiol (CBD) is a major constituent of temperate Cannabis plants and a minor constituent in tropical varieties. At least 113 distinct phytocannabinoids have been isolated from cannabis, although only four (i.e., THCA, CBDA, CBCA and their common precursor CBGA) have been demonstrated to have a biogenetic origin. It was reported in 2020 that phytocannabinoids can be found in other plants such as rhododendron, licorice and liverwort, and earlier in Echinacea. Phytocannabinoids are multi-ring phenolic compounds structurally related to THC, but endocannabinoids are fatty acid derivatives. Nonclassical synthetic cannabinoids (cannabimimetics) include amin ...
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Experimental Drugs
An experiment is a procedure carried out to support or refute a hypothesis, or determine the efficacy or likelihood of something previously untried. Experiments provide insight into cause-and-effect by demonstrating what outcome occurs when a particular factor is manipulated. Experiments vary greatly in goal and scale but always rely on repeatable procedure and logical analysis of the results. There also exist natural experimental studies. A child may carry out basic experiments to understand how things fall to the ground, while teams of scientists may take years of systematic investigation to advance their understanding of a phenomenon. Experiments and other types of hands-on activities are very important to student learning in the science classroom. Experiments can raise test scores and help a student become more engaged and interested in the material they are learning, especially when used over time. Experiments can vary from personal and informal natural comparisons (e. ...
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