N-type Voltage Gated Calcium Channels
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N-type Voltage Gated Calcium Channels
N-type calcium channels also called Cav2.2 channels are voltage gated calcium channels that are localized primarily on the nerve terminals and dendrites as well as neuroendocrine cells. The calcium N-channel consists of several subunits: the primary subunit α1B and the auxiliary subunits α2δ and β. The α1B subunit forms the pore through which the calcium enters and helps to determine most of the channel's properties. These channels play an important role in the neurotransmission during development. In the adult nervous system, N-type calcium channels are critically involved in the release of neurotransmitters, and in pain pathways. N-type calcium channels are the target of ziconotide, the drug prescribed to relieve intractable cancer pain. There are many known N-type calcium channel blockers that function to inhibit channel activity, although the most notable blockers are ω-conotoxins. Structure N-type calcium channels are categorized as high threshold-activated channels ...
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Voltage Gated Calcium Channels
Voltage-gated calcium channels (VGCCs), also known as voltage-dependent calcium channels (VDCCs), are a group of voltage-gated ion channels found in the membrane of excitable cells (''e.g.'', muscle, glial cells, neurons, etc.) with a permeability to the calcium ion Ca2+. These channels are slightly permeable to sodium ions, so they are also called Ca2+-Na+ channels, but their permeability to calcium is about 1000-fold greater than to sodium under normal physiological conditions. At physiologic or resting membrane potential, VGCCs are normally closed. They are activated (''i.e.'': opened) at depolarized membrane potentials and this is the source of the "voltage-gated" epithet. The concentration of calcium (Ca2+ ions) is normally several thousand times higher outside the cell than inside. Activation of particular VGCCs allows a Ca2+ influx into the cell, which, depending on the cell type, results in activation of calcium-sensitive potassium channels, muscular contraction, e ...
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Sympathetic Nervous System
The sympathetic nervous system (SNS) is one of the three divisions of the autonomic nervous system, the others being the parasympathetic nervous system and the enteric nervous system. The enteric nervous system is sometimes considered part of the autonomic nervous system, and sometimes considered an independent system. The autonomic nervous system functions to regulate the body's unconscious actions. The sympathetic nervous system's primary process is to stimulate the body's fight or flight response. It is, however, constantly active at a basic level to maintain homeostasis. The sympathetic nervous system is described as being antagonistic to the parasympathetic nervous system which stimulates the body to "feed and breed" and to (then) "rest-and-digest". Structure There are two kinds of neurons involved in the transmission of any signal through the sympathetic system: pre-ganglionic and post-ganglionic. The shorter preganglionic neurons originate in the thoracolumbar division o ...
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Levetiracetam
Levetiracetam, sold under the brand name Keppra among others, is a medication used to treat epilepsy. It is used for partial-onset, myoclonic, or tonic–clonic seizures and is taken either by mouth as an immediate or extended release formulation or by injection into a vein. Common side effects of levetiracetam include sleepiness, dizziness, feeling tired, and aggression. Severe side effects may include psychosis, suicide, and allergic reactions such as Stevens–Johnson syndrome or anaphylaxis. It is unclear if levetiracetam is safe for use during pregnancy and breastfeeding. Levetiracetam is the S-enantiomer of etiracetam. Its mechanism of action is not yet clear. Levetiracetam was approved for medical use in the United States in 1999 and is available as a generic medication. In 2020, it was the 92nd most commonly prescribed medication in the United States, with more than 7million prescriptions. Medical uses Focal epilepsy Levetiracetam is effective as single-drug treat ...
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Gabapentin
Gabapentin, sold under the brand name Neurontin among others, is an anticonvulsant medication primarily used to treat partial seizures and neuropathic pain. It is a first-line medication for the treatment of neuropathic pain caused by diabetic neuropathy, postherpetic neuralgia, and central pain. It is moderately effective: about 30–40% of those given gabapentin for diabetic neuropathy or postherpetic neuralgia have a meaningful benefit. Sleepiness and dizziness are the most common side effects. Serious side effects include an increased risk of suicide, respiratory depression, and allergic reactions. Lower doses are recommended in those with kidney disease. Gabapentin acts by decreasing activity of a subset of calcium channels. Gabapentin was first approved for use in 1993. It has been available as a generic medication in the United States since 2004. In 2020, it was the tenth most commonly prescribed medication in the United States, with more than 49million prescriptio ...
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Desipramine
Desipramine, sold under the brand name Norpramin among others, is a tricyclic antidepressant (TCA) used in the treatment of depression. It acts as a relatively selective norepinephrine reuptake inhibitor, though it does also have other activities such as weak serotonin reuptake inhibitory, α1-blocking, antihistamine, and anticholinergic effects. The drug is not considered a first-line treatment for depression since the introduction of selective serotonin reuptake inhibitor (SSRI) antidepressants, which have fewer side effects and are safer in overdose. Medical uses Desipramine is primarily used for the treatment of depression. It may also be useful to treat symptoms of attention-deficit hyperactivity disorder (ADHD). Evidence of benefit is only in the short term, and with concerns of side effects its overall usefulness is not clear. Desipramine at very low doses is also used to help reduce the pain associated with functional dyspepsia. It has also been tried, albeit with littl ...
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Cilnidipine
Cilnidipine is a calcium channel blocker. Cilnidipine is approved for use in Japan, China, India, Nepal, and Korea for hypertension. It is a calcium antagonist accompanied with L-type calcium channel, L-type and N-type calcium channel, N-type calcium channel blocking functions. Unlike other calcium antagonists, cilnidipine can act on the N-type calcium channel in addition to acting on the L-type calcium channel. It was patented in 1984 and approved for medical use in 1995. Cilnidipine is currently being repurposed and developed for use in patients with Raynaud's Phenomenon and Systemic Sclerosis by Aisa Pharma, a US biopharma development company. Medical uses Cilnidipine decreases blood pressure and is used to treat hypertension and its Comorbidity, comorbidities. Due to its blocking action at the N-type and L-type calcium channel, cilnidipine dilates both arterioles and venules, reducing the pressure in the capillary bed. Cilnidipine is vasoselective and has a weak direct ...
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Caroverine
Caroverine (Spasmium, Tinnitin, Tinnex) is a muscle-relaxing drug used in Austria and Switzerland to relieve spasms in smooth muscles (which include intestines, arteries, and other organs), and the use in those countries was extended to aid with cerebrovascular diseases there, and eventually to treat tinnitus. It is also used to treat tinnitus in India. Chemically, it is a quinoxalineone and is available in both a base and hydrochloric acid forms. Pharmacologically, it has been described as a nonspecific calcium channel blocker and as an antagonist of both non- NMDA and NMDA glutamate receptor Glutamate receptors are synaptic and non synaptic receptors located primarily on the membranes of neuronal and glial cells. Glutamate (the conjugate base of glutamic acid) is abundant in the human body, but particularly in the nervous system ...s. It was discovered in Austria in the 1950s and was developed by Austrian company Phafag AG. Its INN name, caroverine, was propose ...
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Cadmium
Cadmium is a chemical element with the symbol Cd and atomic number 48. This soft, silvery-white metal is chemically similar to the two other stable metals in group 12, zinc and mercury. Like zinc, it demonstrates oxidation state +2 in most of its compounds, and like mercury, it has a lower melting point than the transition metals in groups 3 through 11. Cadmium and its congeners in group 12 are often not considered transition metals, in that they do not have partly filled ''d'' or ''f'' electron shells in the elemental or common oxidation states. The average concentration of cadmium in Earth's crust is between 0.1 and 0.5 parts per million (ppm). It was discovered in 1817 simultaneously by Stromeyer and Hermann, both in Germany, as an impurity in zinc carbonate. Cadmium occurs as a minor component in most zinc ores and is a byproduct of zinc production. Cadmium was used for a long time as a corrosion-resistant plating on steel, and cadmium compounds are used as red, orang ...
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Conotoxin
A conotoxin is one of a group of neurotoxic peptides isolated from the venom of the marine cone snail, genus ''Conus''. Conotoxins, which are peptides consisting of 10 to 30 amino acid residues, typically have one or more disulfide bonds. Conotoxins have a variety of mechanisms of actions, most of which have not been determined. However, it appears that many of these peptides modulate the activity of ion channels. Over the last few decades conotoxins have been the subject of pharmacological interest. The LD50 of conotoxin ranges from 5-25 μg/kg. Hypervariability Conotoxins are hypervariable even within the same species. They do not act within a body where they are produced (endogenously) but act on other organisms. Therefore, conotoxin genes experience less selection against mutations (like gene duplication and nonsynonymous substitution), and mutations remain in the genome longer, allowing more time for potentially beneficial novel functions to arise. Variability in c ...
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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 ...
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Ziconotide 1DW5
Ziconotide (SNX–111; Prialt), also called intrathecal ziconotide (ITZ) because of its administration route, is an atypical analgesic agent for the amelioration of severe and chronic pain. Derived from ''Conus magus'', a cone snail, it is the synthetic form of an ω-conotoxin peptide. It is 1,000 times as powerful as morphine. In December 2004 the Food and Drug Administration approved ziconotide when delivered as an infusion into the cerebrospinal fluid using an intrathecal pump system. Discovery Ziconotide is derived from the toxin of the cone snail species ''Conus magus''. Scientists have been intrigued by the effects of the thousands of chemicals in marine snail toxins since the initial investigations in the late 1960s by Baldomero Olivera. Olivera, now a professor of biology in the University of Utah, was inspired by accounts of the deadly effects of these toxins from his childhood in the Philippines. Ziconotide was discovered in the early 1980s by University of Utah r ...
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Alcoholism
Alcoholism is, broadly, any drinking of alcohol (drug), alcohol that results in significant Mental health, mental or physical health problems. Because there is disagreement on the definition of the word ''alcoholism'', it is not a recognized diagnostic entity. Predominant diagnostic classifications are alcohol use disorder (DSM-5) or alcohol dependence (ICD-11); these are defined in their respective sources. Excessive alcohol use can damage all organ systems, but it particularly affects the brain, heart, liver, pancreas and immune system. Alcoholism can result in mental illness, delirium tremens, Wernicke–Korsakoff syndrome, Heart arrhythmia, irregular heartbeat, an impaired immune response, liver cirrhosis and alcohol and cancer, increased cancer risk. Drinking during pregnancy can result in fetal alcohol spectrum disorders. Women are generally more sensitive than men to the harmful effects of alcohol, primarily due to their smaller body weight, lower capacity to metaboli ...
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