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Umbellulone
Umbellulone is a headache-inducing monoterpene ketone found in the leaves of the tree '' Umbellularia californica'', sometimes known as the "headache tree". It is hypothesized to cause headaches by influencing the trigeminovascular system via TRPA1. History '' Umbellularia californica'' is a tree native to the coastal forest of California. Botanist Archibald Menzies was the first to collect the oil at the end of the 18th century. In 1826 this tree was classified as a laurel, ''Laurus regia'', by botanist David Douglas. In 1833 the tree received another classification by Hooker and Arnott, ''Tetranthera californica''. Shortly after that the present name was given by Nuttal, ''Umbellularia californica''. In 1875 Heaney obtained a colorless liquid (oreodaphenol) via fractionation under reduced pressure. This oil of the California laurel possess a pungent odor. Stillman (1880) did a fractionation at 215-216 °C. He discovered that inhalation of its fumes can lead to a pain ...
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Umbellularia Californica
''Umbellularia californica'' is a large hardwood tree native to coastal forests and the Sierra foothills of California, and to coastal forests extending into Oregon. It is endemic to the California Floristic Province. It is the sole species in the genus ''Umbellularia''. The tree was formerly known as ''Oreodaphne californica''. In Yuki, it is called pōl’-cum ōl. In Oregon, this tree is known as Oregon myrtle, while in California it is called California bay laurel, which may be shortened to California bay or California laurel. It has also been called pepperwood, spicebush, cinnamon bush, peppernut tree, headache tree, mountain laurel, and balm of heaven. The tree's pungent leaves have a similar flavor to bay leaves, though stronger, and it may be mistaken for bay laurel. The dry wood has a color range from blonde (like maple) to brown (like walnut). It is considered an excellent tonewood and is sought after by luthiers and woodworkers. The tree is a host of the pathogen tha ...
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Monoterpene
Monoterpenes are a class of terpenes that consist of two isoprene units and have the molecular formula C10H16. Monoterpenes may be linear (acyclic) or contain rings (monocyclic and bicyclic). Modified terpenes, such as those containing oxygen functionality or missing a methyl group, are called monoterpenoids. Monoterpenes and monoterpenoids are diverse. They have relevance to the pharmaceutical, cosmetic, agricultural, and food industries. Biosynthesis Monoterpenes are derived biosynthetically from units of isopentenyl pyrophosphate, which is formed from acetyl-CoA via the intermediacy of mevalonic acid in the HMG-CoA reductase pathway. An alternative, unrelated biosynthesis pathway of IPP is known in some bacterial groups and the plastids of plants, the so-called MEP-(2-methyl-D-erythritol-4-phosphate) pathway, which is initiated from C5 sugars. In both pathways, IPP is isomerized to DMAPP by the enzyme isopentenyl pyrophosphate isomerase. Geranyl pyrophosphate is the precu ...
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Monoterpenes
Monoterpenes are a class of terpenes that consist of two isoprene units and have the molecular formula C10H16. Monoterpenes may be linear (acyclic) or contain rings (monocyclic and bicyclic). Modified terpenes, such as those containing oxygen functionality or missing a methyl group, are called monoterpenoids. Monoterpenes and monoterpenoids are diverse. They have relevance to the pharmaceutical, cosmetic, agricultural, and food industries. Biosynthesis Monoterpenes are derived biosynthetically from units of isopentenyl pyrophosphate, which is formed from acetyl-CoA via the intermediacy of mevalonic acid in the HMG-CoA reductase pathway. An alternative, unrelated biosynthesis pathway of IPP is known in some bacterial groups and the plastids of plants, the so-called MEP-(2-methyl-D-erythritol-4-phosphate) pathway, which is initiated from C5 sugars. In both pathways, IPP is isomerized to DMAPP by the enzyme isopentenyl pyrophosphate isomerase. Geranyl pyrophosphate is the precursor ...
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Trigeminovascular System
The trigeminovascular system consists of neurons in the trigeminal nerve that innervate cerebral blood vessels. It has been hypothesized that the trigeminovascular system may be involved in some types of headaches. See also * Umbellulone Umbellulone is a headache-inducing monoterpene ketone found in the leaves of the tree '' Umbellularia californica'', sometimes known as the "headache tree". It is hypothesized to cause headaches by influencing the trigeminovascular system via TR ... References {{reflist External links ''Pain: Current Understanding, Emerging Therapies, and Novel Approaches to Drug Discovery, Second Edition'' by Rajesh Munglani, William K. Schmidt and Chas Bountra, page 321''Functional MRI'' by Chrit T. W. Moonen, P. A. Bandettini, page 21''Craniofacial dysfunction and pain: manual therapy, assessment and management'' by Harry Von Piekartz, Lynn Bryden, page 90 Trigeminal nerve ...
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Trigeminovascular System
The trigeminovascular system consists of neurons in the trigeminal nerve that innervate cerebral blood vessels. It has been hypothesized that the trigeminovascular system may be involved in some types of headaches. See also * Umbellulone Umbellulone is a headache-inducing monoterpene ketone found in the leaves of the tree '' Umbellularia californica'', sometimes known as the "headache tree". It is hypothesized to cause headaches by influencing the trigeminovascular system via TR ... References {{reflist External links ''Pain: Current Understanding, Emerging Therapies, and Novel Approaches to Drug Discovery, Second Edition'' by Rajesh Munglani, William K. Schmidt and Chas Bountra, page 321''Functional MRI'' by Chrit T. W. Moonen, P. A. Bandettini, page 21''Craniofacial dysfunction and pain: manual therapy, assessment and management'' by Harry Von Piekartz, Lynn Bryden, page 90 Trigeminal nerve ...
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Calcitonin Gene-related Peptide
Calcitonin gene-related peptide (CGRP) is a member of the calcitonin family of peptides consisting of calcitonin, amylin, adrenomedullin, adrenomedullin 2 ( intermedin) and calcitonin‑receptor‑stimulating peptide. Calcitonin is mainly produced by thyroid C cells whilst CGRP is secreted and stored in the nervous system. This peptide, in humans, exists in two forms: CGRP alpha (α-CGRP or CGRP I), and CGRP beta (β-CGRP or CGRP II). α-CGRP is a 37-amino acid neuropeptide and is formed by alternative splicing of the calcitonin/CGRP gene located on chromosome 11. β-CGRP is less studied. In humans, β-CGRP differs from α-CGRP by three amino acids and is encoded in a separate, nearby gene. The CGRP family includes calcitonin (CT), adrenomedullin (AM), and amylin (AMY). Function CGRP is produced in both peripheral and central neurons. It is a potent peptide vasodilator and can function in the transmission of nociception. In the spinal cord, the function and expression of CG ...
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Methyl Methacrylate
Methyl methacrylate (MMA) is an organic compound with the formula CH2=C(CH3)COOCH3. This colorless liquid, the methyl ester of methacrylic acid (MAA), is a monomer produced on a large scale for the production of poly(methyl methacrylate) (PMMA). Production and properties Given the scale of production, many methods have been developed starting from diverse two- to four-carbon precursors.. Two principal routes appear to be commonly practiced. Cyanohydrin route The compound is manufactured by several methods, the principal one being the acetone cyanohydrin (ACH) route. ACH is produced by condensation of acetone and hydrogen cyanide. The cyanohydrin is hydrolyzed in the presence of sulfuric acid to a sulfate ester of the methacrylamide. Methanolysis of this ester gives ammonium bisulfate and MMA. Although widely used, the ACH route coproduces substantial amounts of ammonium sulfate. :(CH3)2CO + HCN → (CH3)2C(OH)CN :(CH3)2C(OH)CN + H2SO4 → (CH3)2C(OSO3H)C(O)NH ...
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Aldol Condensation
An aldol condensation is a condensation reaction in organic chemistry in which two carbonyl moieties (of aldehydes or ketones) react to form a β-hydroxyaldehyde or β-hydroxyketone (an aldol reaction), and this is then followed by dehydration to give a conjugated enone. The overall reaction is as follows (where the Rs can be H): Aldol condensations are important in organic synthesis and biochemistry as ways to form carbon–carbon bonds. In its usual form, it involves the nucleophilic addition of a ketone enolate to an aldehyde to form a β-hydroxy ketone, or "aldol" (aldehyde + alcohol), a structural unit found in many naturally occurring molecules and pharmaceuticals. The term ''aldol condensation'' is also commonly used, especially in biochemistry, to refer to just the first (addition) stage of the process—the aldol reaction itself—as catalyzed by aldolases. However, this is formally an addition reaction rather than a condensation reaction because it does not inv ...
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Headache
Headache is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of depression in those with severe headaches. Headaches can occur as a result of many conditions. There are a number of different classification systems for headaches. The most well-recognized is that of the International Headache Society, which classifies it into more than 150 types of primary and secondary headaches. Causes of headaches may include dehydration; fatigue; sleep deprivation; stress; the effects of medications (overuse) and recreational drugs, including withdrawal; viral infections; loud noises; head injury; rapid ingestion of a very cold food or beverage; and dental or sinus issues (such as sinusitis). Treatment of a headache depends on the underlying cause, but commonly involves pain medication (especially in case of migraine or cluster headache). A headache is one of the most commonly experienc ...
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Vasodilation
Vasodilation is the widening of blood vessels. It results from relaxation of smooth muscle cells within the vessel walls, in particular in the large veins, large arteries, and smaller arterioles. The process is the opposite of vasoconstriction, which is the narrowing of blood vessels. When blood vessels dilate, the flow of blood is increased due to a decrease in vascular resistance and increase in cardiac output. Therefore, dilation of arterial blood vessels (mainly the arterioles) decreases blood pressure. The response may be intrinsic (due to local processes in the surrounding tissue) or extrinsic (due to hormones or the nervous system). In addition, the response may be localized to a specific organ (depending on the metabolic needs of a particular tissue, as during strenuous exercise), or it may be systemic (seen throughout the entire systemic circulation). Endogenous substances and drugs that cause vasodilation are termed vasodilators. Such vasoactivity is necessar ...
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TRPM8
Transient receptor potential cation channel subfamily M (melastatin) member 8 (TRPM8), also known as the cold and menthol receptor 1 (CMR1), is a protein that in humans is encoded by the ''TRPM8'' gene. The TRPM8 channel is the primary molecular transducer of cold somatosensation in humans. In addition, mints can desensitize a region through the activation of TRPM8 receptors (the 'cold'/menthol receptor). Structure The TRPM8 channel is a homotetramer, composed of four identical subunits with a transmembrane domain with six helices (S1–6). The first four, S1–4, act as the voltage sensor and allow binding of menthol, icilin and similar channel agonists. S5 and S6 and a connecting loop, also part of the structure, make up the pore, a non-selective cation channel which consists of a highly conserved hydrophobic region. A range of diverse components are required for the high level of specificity in response to cold and menthol stimuli which eventually lead to ion flow through ...
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