|
Discovery And Development Of Triptans
Triptans is a word commonly used for a class of Antimigraine, anti-migraine drugs that are selective serotonin, 5-hydroxytryptamine/serotonin1B/1D (5-HT1B/1D) agonists. Migraine is a complex disease which affects about 15% of the population and can be highly disabling. Triptans have advantages over ergotamine and dihydroergotamine, such as selective pharmacology, well established safety record and Evidence-based medicine, evidence-based prescribing instructions. Triptans are therefore often preferred treatment in migraine. History Search for a new anti-migraine drug started at Glaxo in 1972. Studies in the 1960s showed that vasoconstriction from 5-HT, ergotamine and Norepinephrine, noradrenaline could reduce migraine attacks. Research also showed that platelet 5-HT level is reduced during migraine. Because there are too many side-effects for 5-HT to be used as a drug, scientists started research on the Receptor (biochemistry), receptors of 5-HT in order to discover and develop a mor ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Triptans
Triptans are a family of tryptamine-based medication, drugs used as abortive medication in the treatment of migraines and cluster headaches. This drug class was first commercially introduced in the 1990s. While effective at treating individual headaches, they do not provide preventive treatment and are not considered a cure. They are not effective for the treatment of tension headache, tension–type headache, except in persons who also experience migraines. Triptans do not relieve other kinds of pain. The drugs of this class act as agonists for serotonin 5-HT1B receptor, 5-HT1B and 5-HT1D receptor, 5-HT1D receptors at blood vessels and nerve endings in the brain. The first clinically available triptan was sumatriptan, which has been marketed since 1991. Triptans have largely replaced ergotamines, an older class of medications used to relieve migraine and cluster headaches. Medical uses Migraine Triptans are used for the treatment of severe migraine attacks or those that do no ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Sumatriptan
Sumatriptan, sold commonly under brand names Imitrex and Treximet among others, is a medication used to treat migraine headaches and cluster headaches. It is taken orally, intranasally, or by subcutaneous injection. Therapeutic effects generally occur within three hours. Its primary effect as a serotonin 5-HT1B/1D receptor agonist can create common side effects such as chest pressure, fatigue, vomiting, tingling, and vertigo. Serious side effects may include serotonin syndrome, heart attacks, strokes, and seizures. With excessive medication overuse headaches may occur. It is unclear if use during pregnancy or breastfeeding is safe. The mechanism of action not entirely clear. It is in the triptan class of medications. Sumatriptan was patented in 1982 and approved for medical use in 1991. It is on the World Health Organization's List of Essential Medicines. It is available as a generic medication. In 2020, it was the 111th most commonly prescribed medication in the United ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Aspartic Acid
Aspartic acid (symbol Asp or D; the ionic form is known as aspartate), is an α-amino acid that is used in the biosynthesis of proteins. Like all other amino acids, it contains an amino group and a carboxylic acid. Its α-amino group is in the protonated –NH form under physiological conditions, while its α-carboxylic acid group is deprotonated −COO− under physiological conditions. Aspartic acid has an acidic side chain (CH2COOH) which reacts with other amino acids, enzymes and proteins in the body. Under physiological conditions (pH 7.4) in proteins the side chain usually occurs as the negatively charged aspartate form, −COO−. It is a non-essential amino acid in humans, meaning the body can synthesize it as needed. It is encoded by the codons GAU and GAC. D-Aspartate is one of two D-amino acids commonly found in mammals. .html" ;"title="/sup>">/sup> In proteins aspartate sidechains are often hydrogen bonded to form asx turns or asx motifs, which frequently occur at ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Amino Acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha amino acids appear in the genetic code. Amino acids can be classified according to the locations of the core structural functional groups, as Alpha and beta carbon, alpha- , beta- , gamma- or delta- amino acids; other categories relate to Chemical polarity, polarity, ionization, and side chain group type (aliphatic, Open-chain compound, acyclic, aromatic, containing hydroxyl or sulfur, etc.). In the form of proteins, amino acid '' residues'' form the second-largest component (water being the largest) of human muscles and other tissues. Beyond their role as residues in proteins, amino acids participate in a number of processes such as neurotransmitter transport and biosynthesis. It is thought that they played a key role in enabling life ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Vascular Smooth Muscle
Vascular smooth muscle is the type of smooth muscle that makes up most of the walls of blood vessels. Structure Vascular smooth muscle refers to the particular type of smooth muscle found within, and composing the majority of the wall of blood vessels. Nerve supply Vascular smooth muscle is innervated primarily by the sympathetic nervous system through adrenergic receptors (adrenoceptors). The three types present are: alpha-1, alpha-2 and beta-2 adrenergic receptors, . The main endogenous agonist of these cell receptors is norepinephrine (NE). The adrenergic receptors exert opposite physiologic effects in the vascular smooth muscle under activation: * alpha-1 receptors. Under NE binding alpha-1 receptors cause vasoconstriction ( contraction of the vascular smooth muscle cells decreasing the diameter of the vessels). Thesea receptors are activated in response to shock or low blood pressure as a defensive reaction trying to restore the normal blood pressure. Antagonists ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Central Nervous System
The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all parts of the bodies of bilaterally symmetric and triploblastic animals—that is, all multicellular animals except sponges and diploblasts. It is a structure composed of nervous tissue positioned along the rostral (nose end) to caudal (tail end) axis of the body and may have an enlarged section at the rostral end which is a brain. Only arthropods, cephalopods and vertebrates have a true brain (precursor structures exist in onychophorans, gastropods and lancelets). The rest of this article exclusively discusses the vertebrate central nervous system, which is radically distinct from all other animals. Overview In vertebrates, the brain and spinal cord are both enclosed in the meninges. The meninges provide a barrier to chemicals dissolv ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Ligand-gated Ion Channel
Ligand-gated ion channels (LICs, LGIC), also commonly referred to as ionotropic receptors, are a group of transmembrane ion-channel proteins which open to allow ions such as Na+, K+, Ca2+, and/or Cl− to pass through the membrane in response to the binding of a chemical messenger (i.e. a ligand), such as a neurotransmitter. When a presynaptic neuron is excited, it releases a neurotransmitter from vesicles into the synaptic cleft. The neurotransmitter then binds to receptors located on the postsynaptic neuron. If these receptors are ligand-gated ion channels, a resulting conformational change opens the ion channels, which leads to a flow of ions across the cell membrane. This, in turn, results in either a depolarization, for an excitatory receptor response, or a hyperpolarization, for an inhibitory response. These receptor proteins are typically composed of at least two different domains: a transmembrane domain which includes the ion pore, and an extracellular domain wh ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
G Protein-coupled Receptor
G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large group of evolutionarily-related proteins that are cell surface receptors that detect molecules outside the cell and activate cellular responses. Coupling with G proteins, they are called seven-transmembrane receptors because they pass through the cell membrane seven times. Text was copied from this source, which is available under Attribution 2.5 Generic (CC BY 2.5) license. Ligands can bind either to extracellular N-terminus and loops (e.g. glutamate receptors) or to the binding site within transmembrane helices (Rhodopsin-like family). They are all activated by agonists although a spontaneous auto-activation of an empty receptor can also be observed. G protein-coupled receptors are found only in eukaryotes, including yeast, choanoflagellates, and ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Eletriptan
Eletriptan, sold under the brand name Relpax and used in the form of eletriptan hydrobromide, is a second generation triptan medication intended for treatment of migraine headaches. It is used as an abortive medication, blocking a migraine attack which is already in progress. Eletriptan is marketed and manufactured by Pfizer Inc. Approval and availability Eletriptan was approved by the US Food and Drug Administration (FDA) on December 26, 2002, for the acute treatment of migraine with or without aura in adults. It is available only by prescription in the United States and Canada. It is not intended for the prophylactic therapy of migraine or for use in the management of hemiplegic or basilar migraine. It is available in 20 mg and 40 mg strengths. Eletriptan was covered by and ; both now expired. Mechanism of action Eletriptan is believed to reduce swelling of the blood vessels surrounding the brain. This swelling is associated with the head pain of a migraine att ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Frovatriptan
Frovatriptan, sold under the brand name Frova, is a triptan drug developed by Vernalis for the treatment of migraine headaches and for short term prevention of menstrual migraine. The product is licensed to Endo Pharmaceuticals in North America and Menarini in Europe. Medical uses Frovatriptan is used in the treatment of migraine. Available forms It is available as 2.5 mg tablets. Contraindications Frovatriptan should not be given to patients with: * Ischemic heart disease * Cerebrovascular syndrome * Peripheral vascular disease * Uncontrolled hypertension * Hemiplegic or basilar migraine Side effects Rare, but serious cardiac events have been reported in patients with risk factors predictive of CAD. These include: coronary artery vasospasm, transient myocardial ischemia, myocardial infarction, ventricular tachycardia and ventricular fibrillation. Pharmacology Pharmacodynamics Frovatriptan is a serotonin receptor agonist, with high affinity for the 5-HT1B/1D receptor ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Almotriptan
Almotriptan (trade name Axert and others) is a triptan medication discovered and developed by Almirall for the treatment of heavy migraine headache. It was patented in 1992 and approved for medical use in 2000. Medical uses Almotriptan is prescribed to treat the acute headache phase of migraine attacks with or without aura. Almotriptan is the only oral triptan approved in the US for the treatment of migraine in adolescent from 12 to 17 years of age. Efficacy The efficacy and tolerability of almotriptan has been studied in numerous randomised, controlled trials totaling more than 4800 adults with either moderate or severe attacks of migraine. Its efficacy is significantly more effective than placebo and alleviates nausea, photophobia and phonophobia linked to migraine attacks. Almotriptan has similar efficacy as a standard dose of sumatriptan, another triptan drug, and fewer adverse effects. Contraindications As with other triptans, almotriptan should not be used in pa ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Naratriptan
Naratriptan (trade names include Amerge) is a triptan drug marketed by GlaxoSmithKline and is used for the treatment of migraine headaches. It is a selective 5-HT1 receptor subtype agonist. It was patented in 1987 and approved for medical use in 1997. Medical uses Naratriptan is used for the treatment of the acute migraine attacks and the symptoms of migraine, including severe, throbbing headaches that sometimes are accompanied by nausea and sensitivity to sound or light. Efficacy A meta-analysis of 53 clinical trials has shown that all triptans are effective for treating migraine at marketed doses and that naratriptan, although less effective than sumatriptan and rizatriptan was more effective than placebo in reducing migraine symptoms at two hours and efficacy was demonstrated in almost two thirds of subjects after four hours of treatment. Side effects Side effects include: dizziness, drowsiness, tingling of the hands or feet, nausea, dry mouth and unsteadiness. If these e ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
