Phenoxybenzamine (marketed under the trade name Dibenzyline) is a non-specific, irreversible alpha blocker α blockers or α-antagonists are pharmacological agents that act as antagonists of α adrenergic receptors (α-adrenoceptors).
Uses
It is used in the treatment of hypertension Hypertension or high blood pressure is a chronic medical condition in which the blood pressure in the arteries is elevated. It is the opposite of hypotension. It is classified as either primary (essential) or secondary. About 90-95% of cases are termed "primary hypertension", which refers to high blood pressure for which no medical cause, and specifically that caused by pheochromocytoma A phaeochromocytoma or pheochromocytoma, is a neuroendocrine tumor of the medulla of the adrenal glands (originating in the chromaffin cells), or extra-adrenal chromaffin tissue that failed to involute after birth and secretes excessive amounts of catecholamines, usually adrenaline (epinephrine) if in the adrenal gland and not extra-adrenal, and. It has a slower onset and a longer lasting effect compared with other alpha blockers.
It was also the first alpha blocker α blockers or α-antagonists are pharmacological agents that act as antagonists of α adrenergic receptors (α-adrenoceptors) to be used for treatment of benign prostatic hyperplasia Benign prostatic hyperplasia also known as benign prostatic hypertrophy (technically a misnomer), benign enlargement of the prostate (BEP), and adenofibromyomatous hyperplasia, refers to the increase in size of the prostate in middle-aged and elderly men. To be accurate, the process is one of hyperplasia rather than hypertrophy, but the,[1] although it is currently seldom used for that indication due to unfavourable side effects.
It has been used in the treatment of hypoplastic left heart syndrome.[2]
It is also used in Complex Regional Pain Syndrome Complex regional pain syndrome is a chronic progressive disease characterized by severe pain, swelling and changes in the skin. The International Association for the Study of Pain has divided CRPS into two types based on the presence of nerve lesion following the injury Type 1 due to its anti-adrenergic affects. It has shown to be beneficial if used in the first 3 months of CRPS diagnosis.
Pharmacology
Phenoxybenzamine is used as an anti-hypertensive due to its efficacy in reducing the vasoconstriction caused by adrenaline and noradrenaline. Phenoxybenzamine forms a permanent covalent bond with adrenergic receptors. Based on what we know about the structures of these receptors, it likely involves attack by the cysteine at position 3.36 in transmembrane helix 3 to form a stable linkage.[3] Thus, it remains permanently bound to the receptor, preventing adrenaline and noradrenaline from binding. This causes vasodilatation in blood vessels, due to its antagonistic effect at the alpha-1 adrenoceptor found in the walls of blood vessels, resulting in a drop in blood pressure.
It will also affect the postsynaptic alpha 1 and 2 receptors in the nervous system, and so reduce sympathetic activity. This results in further vasodilation, pupil constriction, an increase in GI tract motility and secretions, and glycogen synthesis.
It also has partial agonist Partial agonists bind and activate a given receptor, but have only partial efficacy at the receptor relative to a full agonist. They may also be considered ligands which display both agonistic and antagonistic effects - when both a full agonist and partial agonist are present, the partial agonist actually acts as a competitive antagonist,/antagonist A receptor antagonist is a type of receptor ligand or drug that does not provoke a biological response itself upon binding to a receptor, but blocks or dampens agonist-mediated responses. In pharmacology, antagonists have affinity but no efficacy for their cognate receptors, and binding will disrupt the interaction and inhibit the function of an properties at the serotonin Serotonin or 5-Hydroxytryptamine (5-HT) is a monoamine neurotransmitter, biochemically derived from tryptophan, that is primarily found in the gastrointestinal (GI) tract, platelets, and central nervous system (CNS) of humans and animals. It is a well-known contributor to feelings of well-being 5-HT2A receptor The mammalian 5-HT2A receptor is a subtype of the 5-HT2 receptor that belongs to the serotonin receptor family and is a G protein-coupled receptor . This is the main excitatory receptor subtype among the GPCRs for serotonin (5-HT), although 5-HT2A may also have an inhibitory effect[citation needed] on certain areas such as the visual cortex and.
References
- ^ Caine M, Perlberg S, Meretyk S (1978). "A placebo-controlled double-blind study of the effect of phenoxybenzamine in benign prostatic obstruction". British journal of urology 50 (7): 551–4. doi A digital object identifier is a character string used to uniquely identify an electronic document or other object. Metadata about the object is stored in association with the DOI name and this metadata may include a location, such as a URL, where the object can be found. The DOI for a document is permanent, whereas its location and other metadata:10.1111/j.1464-410X.1978.tb06210.x. PMID A PMID is a unique number assigned to each PubMed citation of life sciences and biomedical scientific journal articles. The related Pubmed Central archive may additionally assign a separate number, a PMCID (PubMed Central Identifier), normally written with a PMC prefix 88984.
- ^ Guzzetta NA (August 2007). "Phenoxybenzamine in the treatment of hypoplastic left heart syndrome: a core review". Anesth. Analg. 105 (2): 312–5. doi A digital object identifier is a character string used to uniquely identify an electronic document or other object. Metadata about the object is stored in association with the DOI name and this metadata may include a location, such as a URL, where the object can be found. The DOI for a document is permanent, whereas its location and other metadata:10.1213/01.ane.0000275185.44796.92. PMID A PMID is a unique number assigned to each PubMed citation of life sciences and biomedical scientific journal articles. The related Pubmed Central archive may additionally assign a separate number, a PMCID (PubMed Central Identifier), normally written with a PMC prefix 17646482. http://www.anesthesia-analgesia.org/cgi/pmidlookup?view=long&pmid=17646482.
- ^ Frang H, Cockcroft V, Karskela T, Scheinin M, Marjamäki A (2001). "Phenoxybenzamine binding reveals the helical orientation of the third transmembrane domain of adrenergic receptors". J. Biol. Chem. 276 (33): 31279–84. doi A digital object identifier is a character string used to uniquely identify an electronic document or other object. Metadata about the object is stored in association with the DOI name and this metadata may include a location, such as a URL, where the object can be found. The DOI for a document is permanent, whereas its location and other metadata:10.1074/jbc.M104167200. PMID A PMID is a unique number assigned to each PubMed citation of life sciences and biomedical scientific journal articles. The related Pubmed Central archive may additionally assign a separate number, a PMCID (PubMed Central Identifier), normally written with a PMC prefix 11395517.
| Peripheral vasodilators Vasodilation refers to the widening of blood vessels resulting from relaxation of smooth muscle cells within the vessel walls, particularly in the large arteries, smaller arterioles and large veins. The process is essentially the opposite of vasoconstriction, or the narrowing of blood vessels. When vessels dilate, the flow of blood is increased (C04 ATC code C04 Peripheral vasodilators is a therapeutic subgroup of the Anatomical Therapeutic Chemical Classification System, a system of alphanumeric codes developed by the WHO for the classification of drugs and other medical products. Subgroup C04 is part of the anatomical group C Cardiovascular system) |
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| 2-amino-1-phenylethanol derivatives |
Isoxsuprine · Buphenine · Bamethan
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| Imidazoline derivatives/
Alpha blockers α blockers or α-antagonists are pharmacological agents that act as antagonists of α adrenergic receptors (α-adrenoceptors) |
Phentolamine Phentolamine is a reversible nonselective alpha-adrenergic antagonist · Tolazoline Tolazoline is a non-selective competitive α-adrenergic receptor antagonist. It is a vasodilator that is used to treat spasms of peripheral blood vessels . It has also been used successfully as an antidote to reverse the severe peripheral vasoconstriction which can occur as a result of overdose with certain 5-HT2A agonist drugs such as LSD[ · Phenoxybenzamine
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| Niacin and derivatives |
Niacin Niacin is an organic compound with the formula C5H4NCO2H and, depending on the definition used, one of the between forty to eighty essential human nutrients. This colourless, water-soluble solid is a derivative of pyridine, with a carboxyl group (COOH) at the 3-position. Other forms of vitamin B3 include the corresponding amide, nicotinamide (& · Nicotinyl alcohol · Inositol nicotinate · Ciclonicate
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| Purine A purine is a heterocyclic aromatic organic compound, consisting of a pyrimidine ring fused to an imidazole ring. Purines, including substituted purines and their tautomers, are the most widely distributed kind of nitrogen-containing heterocycle in nature derivatives |
Pentifylline · Xantinol nicotinate Xantinol nicotinate is a vasodilator. It is a combination of xanthinol and niacin (nicotinic acid) · Pentoxifylline Pentoxifylline is the International Nonproprietary Name of a drug sold by Aventis under the brand name Trental. Its chemical name is 1-(5-oxohexyl)-3, 7-dimethylxanthine. Pentoxifylline is a xanthine derivative. Other brand names include Pentox, Pentoxil, and Flexital · Etofylline nicotinate
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| Ergot Ergot or ergot fungi refers to a group of fungi of the genus Claviceps. The most prominent member of this group is Claviceps purpurea. This fungus grows on rye and related plants, and produces alkaloids that can cause ergotism in humans and other mammals, consuming grains contaminated with the fruiting structure of this fungus. There are about 50 alkaloids |
Ergoloid · Nicergoline Nicergoline is an ergoloid mesylate derivative used to treat senile dementia and other disorders with vascular origins. It has been found to increase mental agility and enhance clarity and perception. It decreases vascular resistance and increases arterial blood flow in the brain, improving the utilization of oxygen and glucose by brain cells. It · Dihydroergocristine
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Cyclandelate · Phenoxybenzamine · Vincamine Vincamine is a peripheral vasodilator that increases blood flow to the brain. It is an indole alkaloid found in the leaves of Vinca minor, comprising about 25-65% of the indole alkaloids found in Vinca minor by weight. It is also found in the species Catharanthus roseus. It can be synthesized from related alkaloids · Moxisylyte · Bencyclane · Vinburnine · Sulcotidil · Buflomedil Categories: Vasodilators | Pyrrolidines | Ketones | Phenol ethers | · Naftidrofuryl · Butalamine · Visnadine Visnadine is a natural vasodilator. It was first isolated from bishop's weed (Ammi visnaga), a plant indigenous to the Mediterranean region which has been used for centuries in Egypt as a spasmolytic · Cetiedil · Cinepazide · Ifenprodil · Azapetine · Fasudil
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| Receptor In biochemistry, a receptor is a protein molecule, embedded in either the plasma membrane or the cytoplasm of a cell, to which one or more specific kinds of signaling molecules may attach. A molecule which binds to a receptor is called a ligand, and may be a peptide (short protein) or other small molecule, such as a neurotransmitter, a hormone, a
Ligands In coordination chemistry, a ligand is an ion, or molecule that binds to a central metal-atom to form a coordination complex. The bonding between metal and ligand generally involves formal donation of one or more of the ligand's electron pairs. The metal-ligand bonding can range from covalent to more ionic. Furthermore, the metal-ligand bond order |
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α The adrenergic receptors are a class of G protein-coupled receptors that are targets of the catecholamines, especially noradrenaline (norepinephrine) and adrenaline (epinephrine). Although dopamine is a catecholamine, its receptors are in a different category
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α1 The alpha-1 adrenergic receptor is a G protein-coupled receptor (GPCR) associated with the Gq heterotrimeric G-protein. It consists of three highly homologous subtypes, including α1A-, α1B-, and α1D-adrenergic. Catecholamines like norepinephrine (noradrenaline) and epinephrine (adrenaline) signal through the α1-adrenergic receptor in the
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Agonists: Amidephrine Categories: Drugs not assigned an ATC code | Alpha-adrenergic agonists | Amines | Sulfonamides | Phenethylamines | • Cirazoline Cirazoline is a nonselective agonist of the alpha-1 adrenergic receptor , and an antagonist to the alpha-2 adrenergic receptor. It is believed that this combination of properties could make cirazoline an effective effective vasoconstricting agent • Dopamine Dopamine is a catecholamine neurotransmitter that occurs in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this phenethylamine functions as a neurotransmitter, activating the five types of dopamine receptors—D1, D2, D3, D4, and D5—and their variants. Dopamine is produced in several areas of the brain, • Epinephrine Epinephrine is a hormone and neurotransmitter.. It increases heart rate, contracts blood vessels, dilates air passages and participates in the fight-or-flight response of the sympathetic nervous system. Chemically, epinephrine is a catecholamine, a monoamine produced only by the adrenal glands from the amino acids phenylalanine and tyrosine (Adrenaline) • Etilefrine Etilefrine, (2-ethylamino-1~ ethanol, is a sympathomimetic amine of the 3-hydroxy- phenylethanolamine series used in treating orthostatic hypotension of neurological, cardiovascular, endocrine or metabolic origin. Intravenous infusion of this compound increases cardiac output, stroke volume, venous return and blood pressure in man and experimental • Isoprenaline Isoprenaline or isoproterenol (USAN, trade names Medihaler-Iso and Isuprel) is a sympathomimetic beta adrenergic agonist medication • Levonordefrin Levonordefrin , also known as α-Methylnorepinephrine (α-Me-NE), is a drug used as a topical nasal decongestant and vasoconstrictor in dentistry. It is also a metabolite of the antihypertensive drug methyldopa, and plays a crucial role in its pharmacology and therapeutic benefits • Metaraminol Metaraminol is a potent sympathomimetic amine used in the prevention and treatment of hypotension, particularly as a complication of anesthesia. It is an α1-adrenergic receptor agonist with some β effect • Methoxamine Methoxamine is an α1-adrenergic receptor agonist, similar in structure to phenylephrine and 2,5-DMA. It induces vasoconstriction of skin and splanchnic blood vessels, thereby increasing peripheral vascular resistance and raising mean arterial blood pressure. Because of its hypertensive effects, it may evoke a compensatory reflex bradycardia via • Methyldopa Methyldopa is a psychoactive drug used as a sympatholytic or antihypertensive. Its use is now deprecated following introduction of alternative safer classes of agents. However, it continues to have a role in otherwise difficult to treat hypertension and gestational hypertension (also known as pregnancy-induced hypertension (PIH)) • Norepinephrine Norepinephrine (abbreviated norepi or NE) or noradrenaline (BAN) (abbreviated NA or NAd) is a catecholamine with multiple roles including as a hormone and a neurotransmitter (Noradrenaline) • Oxymetazoline Oxymetazoline is available over-the-counter as a topical decongestant in the form of oxymetazoline hydrochloride in nasal sprays such as Afrin, Sudafed OM, Dristan, Vicks Sinex, and Mucinex Full Force. It was developed from Xylometazoline at E.Merck Darmstadt by Fruhstorfer in 1961 • Phenylephrine Phenylephrine or Neo-Synephrine is an α1-adrenergic receptor agonist used primarily as a decongestant, as an agent to dilate the pupil, and to increase blood pressure. Phenylephrine has recently been marketed as a substitute for pseudoephedrine (e.g.,Sudafed ), but there are recent claims that oral phenylephrine may be no more effective as a
Antagonists: Alfuzosin Alfuzosin is an α1 receptor antagonist used to treat benign prostatic hyperplasia (BPH). It works by relaxing the muscles in the prostate and bladder neck, making it easier to urinate • Arotinolol Arotinolol is a medication in the class of mixed alpha/beta blockers • Carvedilol • Doxazosin • Indoramin • L-765,314 • Labetalol • Moxisylyte • Nantenine • Phentolamine • Phenoxybenzamine • Prazosin • Silodosin • Tamsulosin • Terazosin • Tolazoline • Trimazosin • Urapidil
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α2
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Agonists: (R)-3-Nitrobiphenyline • 4-NEMD • Amitraz • Apraclonidine • Brimonidine • Clonidine • Detomidine • Dexmedetomidine • Dopamine • Epinephrine (Adrenaline) • Etilefrine • Guanabenz • Guanfacine • Guanethidine • Guanoxabenz • Levonordefrin • Lofexidine • Medetomidine • Methyldopa • Norepinephrine (Noradrenaline) • Octopamine • Romifidine • Tizanidine • Tolonidine • Xylazine • Xylometazoline
Antagonists: 1-PP • Atipamezole • BRL-44408 • Buspirone • Cirazoline • Efaroxan • Gepirone • Idazoxan • Ipsapirone • Mianserin • Mirtazapine • NAN-190 • Phentolamine • Phenoxybenzamine • Rauwolscine • SB-269,970 • Setiptiline • Spiroxatrine • Tandospirone • Tolazoline • Yohimbine
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Agonists: Anisodamine • Ephedrine • Ergotamine • Indanidine • Mephentermine • Midodrine • Mivazerol • Naphazoline • Phenylpropanolamine • Pseudoephedrine • Rilmenidine • Synephrine • Talipexole • Tetrahydrozoline
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Oxazolines: 4-Methylaminorex (4-MAR, 4-MAX) • Aminorex • Clominorex • Cyclazodone • Fenozolone • Fluminorex • Pemoline • Thozalinone; Phenethylamines (also Amphetamines, Cathinones, Phentermines, etc): 2-Hydroxyphenethylamine (2-OH-PEA) • 4-Methylamphetamine (4-MA) • 4-Methylmethamphetamine (4-MMA) • Alfetamine • Amphetamine (Dextroamphetamine, Levoamphetamine) • Amphetaminil • Amfepentorex • β-Methylphenethylamine (β-Me-PEA) • Benzodioxolylbutanamine (BDB) • Benzodioxolylhydroxybutanamine (BOH) • Benzphetamine • Buphedrone • Butylone • Cathine • Cathinone • Clobenzorex • Clortermine • Diethylcathinone (Diethylpropion, Amfepramone) • Dimethoxyamphetamine (DMA) • Dimethoxymethamphetamine (DMMA) • Dimethylamphetamine • Dimethylcathinone (Dimethylpropion, Metamfepramone) • Ephedrine (EPH) • Ethcathinone (Ethylpropion) • Ethylamphetamine • Ethylbenzodioxolylbutanamine (EBDB) • Ethylone • Fenethylline • Fenproporex • Flephedrone • Fludorex • Furfenorex • Hordenine • Indanorex • Indanylamphetamine (IAP) • Lisdexamfetamine • Lophophine (Homomyristicylamine) • Mefenorex • Mephedrone • Mephentermine • Methamphetamine (Desoxyephedrine, Methedrine; Dextromethamphetamine, Levomethamphetamine) • Methcathinone (Methylpropion) • Methedrone • Methoxymethylenedioxyamphetamine (MMDA) • Methoxymethylenedioxymethamphetamine (MMDMA) • Methylbenzodioxolylbutanamine (MBDB) • Methylenedioxyamphetamine (MDA; Tenamfetamine) • Methylenedioxyethylamphetamine (MDEA) • Methylenedioxyhydroxyamphetamine (MDOH) • Methylenedioxymethamphetamine (MDMA) • Methylenedioxymethylphenethylamine (MDMPEA; Homarylamine) • Methylenedioxyphenethylamine (MDPEA; Homopiperonylamine) • Methylone • Naphthylamphetamine (NAP) • Ortetamine • Oxaflozane • Parabromoamphetamine (PBA) • Parachloroamphetamine (PCA) • Parafluoroamphetamine (PFA) • Parafluoromethamphetamine (PFMA) • Parahydroxyamphetamine (PHA) • Paraiodoamphetamine (PIA) • Paramethoxyamphetamine (PMA) • Paramethoxyethylamphetamine (PMEA) • Paramethoxymethamphetamine (PMMA) • Paredrine (Norpholedrine, Oxamphetamine) • Phendimetrazine • Phenethylamine (PEA) • Phenmetrazine • Pholedrine • Phenpentermine • Phenpromethamine • Phentermine • Phenylpropanolamine (PPA) • Propylamphetamine • Pseudoephedrine (PSE) • Tiflorex (Flutiorex) • Tyramine (TRA) • Xylopropamine • Zylofuramine; Piperazines: 2,5-Dimethoxy-4-bromobenzylpiperazine (2C-B-BZP) • Benzylpiperazine (BZP) • Methoxyphenylpiperazine (MeOPP; Paraperazine) • Methylbenzylpiperazine (MBZP) • Methylenedioxybenzylpiperazine (MDBZP; Piperonylpiperazine) • Parafluorophenylpiperazine (pFPP; Fluoperazine); Others: 2-Aminoindane (2-AI) • 2-Aminotetralin (2-AT) • 2-Benzylpiperidine (2-BP) • 4-Benzylpiperidine (4-BP) • Clofenciclan • Cyclopentamine • Cypenamine • Cyprodenate • Feprosidnine • Gilutensin • Heptaminol • Hexacyclonate • Isometheptene • Methylhexanamine • Octodrine • Phthalimidopropiophenone • Propylhexedrine (PHX) • Tuaminoheptane (Tuamine)
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Categories: Drugboxes which contain changes to watched fields | Alpha blockers | IARC Group 2B carcinogens
