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Rolipram
Rolipram is a selective phosphodiesterase-4 inhibitor discovered and developed by Schering AG as a potential antidepressant drug in the early 1990s. It served as a prototype molecule for several companies' drug discovery and development efforts.McKenna, JM and Muller, GW. Medicinal Chemistry of PDE4 Inhibitors. Chapter 33 in Cyclic Nucleotide Phosphodiesterases in Health and Disease, Eds Joseph A. Beavo et al. CRC Press, Dec 5, 2006 Rolipram was discontinued after clinical trials showed that its therapeutic window was too narrow; it could not be dosed at high enough levels to be effective without causing significant gastrointestinal side effects. Rolipram has several activities that make it a continuing focus for research. The etiology of many neurodegenerative diseases involves misfolded and clumped proteins which accumulate in the brain. Cells have a mechanism to dispose of such proteins called the proteasome. However, in Alzheimer's disease and some other conditions t ...
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Phosphodiesterase-4 Inhibitor
A phosphodiesterase-4 inhibitor, commonly referred to as a PDE4 inhibitor, is a drug used to block the degradative action of phosphodiesterase 4 (PDE4) on cyclic adenosine monophosphate (cAMP). It is a member of the larger family of Phosphodiesterase inhibitor, PDE inhibitors. The PDE4 family of enzymes are the most prevalent PDE in immune cells. They are predominantly responsible for hydrolyzing cAMP within both immune cells and cells in the central nervous system. Therapeutic utility The prototypical PDE4 inhibitor is rolipram. PDE4 inhibitors are known to possess procognitive (including long term memory-improving), wakefulness-promoting, neuroprotective, and anti-inflammatory effects. Consequently, PDE4 inhibitors have been investigated as treatments for a diverse group of different diseases, including central nervous system disorders such as major depressive disorder (clinical depression), anxiety disorders, schizophrenia, Parkinson's disease, Alzheimer's disease, multiple scl ...
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Liver
The liver is a major Organ (anatomy), organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it is located in the quadrant (anatomy), right upper quadrant of the abdomen, below the thoracic diaphragm, diaphragm. Its other roles in metabolism include the regulation of Glycogen, glycogen storage, decomposition of red blood cells, and the production of hormones. The liver is an accessory digestive organ that produces bile, an alkaline fluid containing cholesterol and bile acids, which helps the fatty acid degradation, breakdown of fat. The gallbladder, a small pouch that sits just under the liver, stores bile produced by the liver which is later moved to the small intestine to complete digestion. The liver's highly specialized biological tissue, tissue, consisting mostly of hepatocytes, regulates a w ...
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Alzheimer's Disease
Alzheimer's disease (AD) is a neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term memory, remembering recent events. As the disease advances, symptoms can include primary progressive aphasia, problems with language, Orientation (mental), disorientation (including easily getting lost), mood swings, loss of motivation, self-neglect, and challenging behaviour, behavioral issues. As a person's condition declines, they often withdraw from family and society. Gradually, bodily functions are lost, ultimately leading to death. Although the speed of progression can vary, the typical life expectancy following diagnosis is three to nine years. The cause of Alzheimer's disease is poorly understood. There are many environmental and genetic risk factors associated with its development. The strongest genetic risk factor is from an alle ...
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Phenol Ethers
Phenol (also called carbolic acid) is an aromatic organic compound with the molecular formula . It is a white crystalline solid that is volatile. The molecule consists of a phenyl group () bonded to a hydroxy group (). Mildly acidic, it requires careful handling because it can cause chemical burns. Phenol was first extracted from coal tar, but today is produced on a large scale (about 7 billion kg/year) from petroleum-derived feedstocks. It is an important industrial commodity as a precursor to many materials and useful compounds. It is primarily used to synthesize plastics and related materials. Phenol and its chemical derivatives are essential for production of polycarbonates, epoxies, Bakelite, nylon, detergents, herbicides such as phenoxy herbicides, and numerous pharmaceutical drugs. Properties Phenol is an organic compound appreciably soluble in water, with about 84.2 g dissolving in 1000 mL (0.895 M). Homogeneous mixtures of phenol and water at phenol to ...
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PDE4 Inhibitors
At least four types of the enzyme phosphodiesterase 4 (PDE4) are known: * PDE4A * PDE4B * PDE4C * PDE4D See also * 3',5'-cyclic-AMP phosphodiesterase * Phosphodiesterase (PDE) * PDE4 inhibitor A phosphodiesterase-4 inhibitor, commonly referred to as a PDE4 inhibitor, is a drug used to block the degradative action of phosphodiesterase 4 (PDE4) on cyclic adenosine monophosphate (cAMP). It is a member of the larger family of PDE inhibitor ... {{chemistry index Molecular biology ...
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Abandoned Drugs
Abandon, abandoned, or abandonment may refer to: Common uses * Abandonment (emotional), a subjective emotional state in which people feel undesired, left behind, insecure, or discarded * Abandonment (legal), a legal term regarding property ** Child abandonment, the extralegal abandonment of children ** Lost, mislaid, and abandoned property, legal status of property after abandonment and rediscovery * Abandonment (mysticism) Art, entertainment, and media Film * ''Abandon'' (film), a 2002 film starring Katie Holmes * ''Abandoned'' (1949 film), starring Dennis O'Keefe * ''Abandoned'' (1955 film), the English language title of the Italian war film ''Gli Sbandati'' * ''Abandoned'' (2001 film), a Hungarian film * ''Abandoned'' (2010 film), starring Brittany Murphy * ''Abandoned'' (2015 film), a television movie about the shipwreck of the ''Rose-Noëlle'' in 1989 * ''Abandoned'' (2022 film), starring Emma Roberts * ''The Abandoned'' (1945 film), a 1945 Mexican film * ''The Aban ...
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Roflumilast
Roflumilast, sold under the trade name Daxas among others, is a drug that acts as a selective, long-acting inhibitor of the enzyme phosphodiesterase-4 (PDE-4). It has anti-inflammatory effects and is used as an orally administered drug for the treatment of inflammatory conditions of the lungs such as chronic obstructive pulmonary disease (COPD). In June 2010, it was approved in the European Union for severe COPD associated with chronic bronchitis. In February 2011, it gained FDA approval in the United States for reducing COPD exacerbations. It is available as a generic medication. Medical uses Roflumilast is indicated In medicine, an indication is a valid reason to use a certain test, medication, procedure, or surgery. There can be multiple indications to use a procedure or medication. An indication can commonly be confused with the term diagnosis. A diagnosis ... for the treatment of severe chronic obstructive pulmonary disease (COPD) and for the treatment of plaque psorias ...
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COPD
Chronic obstructive pulmonary disease (COPD) is a type of progressive lung disease characterized by long-term respiratory symptoms and airflow limitation. The main symptoms include shortness of breath and a cough, which may or may not produce mucus. COPD progressively worsens, with everyday activities such as walking or dressing becoming difficult. While COPD is incurable, it is preventable and treatable. The two most common conditions of COPD are emphysema and chronic bronchitis and they have been the two classic COPD phenotypes. Emphysema is defined as enlarged airspaces (alveoli) whose walls have broken down resulting in permanent damage to the lung tissue. Chronic bronchitis is defined as a productive cough that is present for at least three months each year for two years. Both of these conditions can exist without airflow limitation when they are not classed as COPD. Emphysema is just one of the structural abnormalities that can limit airflow and can exist without airflow ...
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Asthma
Asthma is a long-term inflammatory disease of the airways of the lungs. It is characterized by variable and recurring symptoms, reversible airflow obstruction, and easily triggered bronchospasms. Symptoms include episodes of wheezing, coughing, chest tightness, and shortness of breath. These may occur a few times a day or a few times per week. Depending on the person, asthma symptoms may become worse at night or with exercise. Asthma is thought to be caused by a combination of genetic and environmental factors. Environmental factors include exposure to air pollution and allergens. Other potential triggers include medications such as aspirin and beta blockers. Diagnosis is usually based on the pattern of symptoms, response to therapy over time, and spirometry lung function testing. Asthma is classified according to the frequency of symptoms, forced expiratory volume in one second (FEV1), and peak expiratory flow rate. It may also be classified as atopic or non-atopic, ...
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Autoimmune Diseases
An autoimmune disease is a condition arising from an abnormal immune response to a functioning body part. At least 80 types of autoimmune diseases have been identified, with some evidence suggesting that there may be more than 100 types. Nearly any body part can be involved. Common symptoms can be diverse and transient, ranging from mild to severe, and generally include low grade fever and feeling tired. The cause is unknown. Some autoimmune diseases such as lupus run in families, and certain cases may be triggered by infections or other environmental factors. Some common diseases that are generally considered autoimmune include celiac disease, diabetes mellitus type 1, graves' disease, inflammatory bowel disease, multiple sclerosis, alopecia areata, addison’s disease, pernicious anemia, psoriasis, rheumatoid arthritis, and systemic lupus erythematosus. The diagnosis can be difficult to determine. Treatment depends on the type and severity of the condition. Nonsteroidal ant ...
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Neurodegenerative Diseases
A neurodegenerative disease is caused by the progressive loss of structure or function of neurons, in the process known as neurodegeneration. Such neuronal damage may ultimately involve cell death. Neurodegenerative diseases include amyotrophic lateral sclerosis, multiple sclerosis, Parkinson's disease, Alzheimer's disease, Huntington's disease, multiple system atrophy, and prion diseases. Neurodegeneration can be found in the brain at many different levels of neuronal circuitry, ranging from molecular to systemic. Because there is no known way to reverse the progressive degeneration of neurons, these diseases are considered to be incurable; however research has shown that the two major contributing factors to neurodegeneration are oxidative stress and inflammation. Biomedical research has revealed many similarities between these diseases at the subcellular level, including atypical protein assemblies (like proteinopathy) and induced cell death. These similarities suggest that th ...
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Proteasome
Proteasomes are protein complexes which degrade unneeded or damaged proteins by proteolysis, a chemical reaction that breaks peptide bonds. Enzymes that help such reactions are called proteases. Proteasomes are part of a major mechanism by which cells regulate the concentration of particular proteins and degrade misfolded proteins. Proteins are tagged for degradation with a small protein called ubiquitin. The tagging reaction is catalyzed by enzymes called ubiquitin ligases. Once a protein is tagged with a single ubiquitin molecule, this is a signal to other ligases to attach additional ubiquitin molecules. The result is a ''polyubiquitin chain'' that is bound by the proteasome, allowing it to degrade the tagged protein. The degradation process yields peptides of about seven to eight amino acids long, which can then be further degraded into shorter amino acid sequences and used in synthesizing new proteins. Proteasomes are found inside all eukaryotes and archaea, and in so ...
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