Phenoxybenzamine

Common Name

Phenoxybenzamine Description

Phenoxybenzamine is only found in individuals that have used or taken this drug. It is an alpha-adrenergic antagonist with long duration of action. It has been used to treat hypertension and as a peripheral vasodilator. [PubChem]Phenoxybenzamine produces its therapeutic actions by blocking alpha receptors, leading to a muscle relaxation and a widening of the blood vessels. This widening of the blood vessels reslits in a lowering of blood pressure. Structure

Synonyms

Value Source FenossibenzaminaHMDB DibenylineMeSH Hydrochloride, phenoxybenzamineMeSH DibenyleneMeSH DibenziranMeSH Goldshield brand OF phenoxybenzamine hydrochlorideMeSH Link brand OF phenoxybenzamine hydrochlorideMeSH Esparma brand OF phenoxybenzamine hydrochlorideMeSH DibenzylineMeSH Phenoxybenzamine hydrochlorideMeSH Wellspring brand OF phenoxybenzamine hydrochlorideMeSH DibenzylinMeSH DibenzyranMeSH

Chemical Formlia

C₁₈H₂₂ClNO Average Molecliar Weight

303.826 Monoisotopic Molecliar Weight

303.138992038 IUPAC Name

benzyl(2-chloroethyl)(1-phenoxypropan-2-yl)amine Traditional Name

phenoxybenzamine CAS Registry Number

59-96-1 SMILES

InChI Identifier

InChI Key

QZVCTJOXCFMACW-UHFFFAOYSA-N Chemical Taxonomy Description

This compound belongs to the class of chemical entities known as phenylmethylamines. These are compounds containing a phenylmethtylamine moiety, which consists of a phenyl group substituted by an methanamine. Kingdom

Chemical entities Super Class

Organic compounds Class

Benzenoids Sub Class

Benzene and substituted derivatives Direct Parent

Phenylmethylamines Alternative Parents

Phenoxy compounds

Phenol ethers

Benzylamines

Aralkylamines

Alkyl aryl ethers

Trialkylamines

Organopnictogen compounds

Organochlorides

Hydrocarbon derivatives

Alkyl chlorides

Substituents

Benzylamine

Phenoxy compound

Phenol ether

Phenylmethylamine

Alkyl aryl ether

Aralkylamine

Tertiary aliphatic amine

Tertiary amine

Ether

Organopnictogen compound

Organic oxygen compound

Organooxygen compound

Organonitrogen compound

Organochloride

Organohalogen compound

Organic nitrogen compound

Amine

Alkyl halide

Alkyl chloride

Hydrocarbon derivative

Aromatic homomonocyclic compound

Molecliar Framework

Aromatic homomonocyclic compounds External Descriptors

aromatic amine (CHEBI:8077 )

Ontology Status

Expected but not Quantified Origin

Drug

Biofunction

Adrenergic alpha-Antagonists

Antihypertensive Agents

Vasodilator Agents

Application

Pharmaceutical

Cellliar locations

Membrane

Physical Properties State

Solid Experimental Properties

Property Value Reference Melting Point39 °CNot Available Boiling PointNot AvailableNot Available Water Solubility1.03e-02 g/LNot Available LogP4.7Not Available

Predicted Properties

Property Value Source Water Solubility0.01 mg/mLALOGPS logP4.26ALOGPS logP4.64ChemAxon logS-4.5ALOGPS pKa (Strongest Basic)7.97ChemAxon Physiological Charge1ChemAxon Hydrogen Acceptor Count2ChemAxon Hydrogen Donor Count0ChemAxon Polar Surface Area12.47 ŲChemAxon Rotatable Bond Count8ChemAxon Refractivity88.92 m³·mol^-1ChemAxon Polarizability34.09 ųChemAxon Number of Rings2ChemAxon Bioavailability1ChemAxon Rlie of FiveYesChemAxon Ghose FilterYesChemAxon Vebers RlieYesChemAxon MDDR-like RlieYesChemAxon

Spectra Spectra

Spectrum Type Description Splash Key Predicted LC-MS/MS

Predicted LC-MS/MS Spectrum – 10V, PositiveNot Available Predicted LC-MS/MS

Predicted LC-MS/MS Spectrum – 20V, PositiveNot Available Predicted LC-MS/MS

Predicted LC-MS/MS Spectrum – 40V, PositiveNot Available Predicted LC-MS/MS

Predicted LC-MS/MS Spectrum – 10V, NegativeNot Available Predicted LC-MS/MS

Predicted LC-MS/MS Spectrum – 20V, NegativeNot Available Predicted LC-MS/MS

Predicted LC-MS/MS Spectrum – 40V, NegativeNot Available

Biological Properties Cellliar Locations

Membrane

Biofluid Locations

Blood

Urine

Tissue Location

Not Available Pathways

Not Available Normal Concentrations

Biofluid Status Value Age Sex Condition Reference Details BloodExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB00925

21059682

details UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB00925

21059682

details

Abnormal Concentrations

Not Available Associated Disorders and Diseases Disease References

None Associated OMIM IDs

None External Links DrugBank ID

DB00925 DrugBank Metabolite ID

Not Available Phenol Explorer Compound ID

Not Available Phenol Explorer Metabolite ID

Not Available FoodDB ID

Not Available KNApSAcK ID

Not Available Chemspider ID

4604 KEGG Compound ID

C07435 BioCyc ID

Not Available BiGG ID

Not Available Wikipedia Link

Phenoxybenzamine NuGOwiki Link

HMDB15061 Metagene Link

HMDB15061 METLIN ID

Not Available PubChem Compound

4768 PDB ID

Not Available ChEBI ID

141434

Product: THZ3

References Synthesis Reference Not Available Material Safety Data Sheet (MSDS) Not Available General References

1. Frang H, Cockcroft V, Karskela T, Scheinin M, Marjamaki A: Phenoxybenzamine binding reveals the helical orientation of the third transmembrane domain of adrenergic receptors. J Biol Chem. 2001 Aug 17;276(33):31279-84. Epub 2001 Jun 6. [PubMed:11395517 ]
2. Caine M, Perlberg S, Meretyk S: A placebo-controlled double-blind study of the effect of phenoxybenzamine in benign prostatic obstruction. Br J Urol. 1978 Dec;50(7):551-4. [PubMed:88984 ]

Enzymes

General function:

Involved in monooxygenase activity

Specific function:

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.

Gene Name:

CYP3A4

Uniprot ID:

P08684

Molecular weight:

57255.585

References

1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]

General function:

Involved in G-protein coupled receptor protein signaling pathway

Specific function:

Alpha-2 adrenergic receptors mediate the catecholamine- induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is oxymetazoline > clonidine > epinephrine > norepinephrine > phenylephrine > dopamine > p-synephrine > p-tyramine > serotonin = p-octopamine. For antagonists, the rank order is yohimbine > phentolamine = mianserine > chlorpromazine = spiperone = prazosin > propanolol > alprenolol = pindolol

Gene Name:

ADRA2A

Uniprot ID:

P08913

Molecular weight:

48956.3

References

1. Frang H, Cockcroft V, Karskela T, Scheinin M, Marjamaki A: Phenoxybenzamine binding reveals the helical orientation of the third transmembrane domain of adrenergic receptors. J Biol Chem. 2001 Aug 17;276(33):31279-84. Epub 2001 Jun 6. [PubMed:11395517 ]

General function:

Involved in G-protein coupled receptor protein signaling pathway

Specific function:

Alpha-2 adrenergic receptors mediate the catecholamine- induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is clonidine > norepinephrine > epinephrine = oxymetazoline > dopamine > p-tyramine = phenylephrine > serotonin > p-synephrine / p-octopamine. For antagonists, the rank order is yohimbine > chlorpromazine > phentolamine > mianserine > spiperone > prazosin > alprenolol > propanolol > pindolol

Gene Name:

ADRA2B

Uniprot ID:

P18089

Molecular weight:

49953.1

References

1. Frang H, Cockcroft V, Karskela T, Scheinin M, Marjamaki A: Phenoxybenzamine binding reveals the helical orientation of the third transmembrane domain of adrenergic receptors. J Biol Chem. 2001 Aug 17;276(33):31279-84. Epub 2001 Jun 6. [PubMed:11395517 ]

General function:

Involved in G-protein coupled receptor protein signaling pathway

Specific function:

Beta-adrenergic receptors mediate the catecholamine- induced activation of adenylate cyclase through the action of G proteins. The beta-2-adrenergic receptor binds epinephrine with an approximately 30-fold greater affinity than it does norepinephrine

Gene Name:

ADRB2

Uniprot ID:

P07550

Molecular weight:

46458.3

References

1. Frang H, Cockcroft V, Karskela T, Scheinin M, Marjamaki A: Phenoxybenzamine binding reveals the helical orientation of the third transmembrane domain of adrenergic receptors. J Biol Chem. 2001 Aug 17;276(33):31279-84. Epub 2001 Jun 6. [PubMed:11395517 ]

General function:

Involved in calcium ion binding

Specific function:

Calmodulin mediates the control of a large number of enzymes and other proteins by Ca(2+). Among the enzymes to be stimulated by the calmodulin-Ca(2+) complex are a number of protein kinases and phosphatases. Together with CEP110 and centrin, is involved in a genetic pathway that regulates the centrosome cycle and progression through cytokinesis

Gene Name:

CALM1

Uniprot ID:

P62158

Molecular weight:

16837.5

References

1. Cimino M, Weiss B: Characteristics of the binding of phenoxybenzamine to calmodulin. Biochem Pharmacol. 1988 Jul 15;37(14):2739-45. [PubMed:3134891 ]
2. Suko J, Wyskovsky W, Pidlich J, Hauptner R, Plank B, Hellmann G: Calcium release from calmodulin and its C-terminal or N-terminal halves in the presence of the calmodulin antagonists phenoxybenzamine and melittin measured by stopped-flow fluorescence with Quin 2 and intrinsic tyrosine. Inhibition of calmodulin-dependent protein kinase of cardiac sarcoplasmic reticulum. Eur J Biochem. 1986 Sep 15;159(3):425-34. [PubMed:3758070 ]
3. Lukas TJ, Marshak DR, Watterson DM: Drug-protein interactions: isolation and characterization of covalent adducts of phenoxybenzamine and calmodulin. Biochemistry. 1985 Jan 1;24(1):151-7. [PubMed:3994963 ]
4. Earl CQ, Prozialeck WC, Weiss B: Interaction of alpha adrenergic antagonists with calmodulin. Life Sci. 1984 Jul 30;35(5):525-34. [PubMed:6146911 ]
5. Kuromi H, Yoshihara M, Kidokoro Y: An inhibitory role of calcineurin in endocytosis of synaptic vesicles at nerve terminals of Drosophila larvae. Neurosci Res. 1997 Feb;27(2):101-13. [PubMed:9100252 ]

General function:

Involved in G-protein coupled receptor protein signaling pathway

Specific function:

This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol- calcium second messenger system. Its effect is mediated by G(q) and G(11) proteins

Gene Name:

ADRA1A

Uniprot ID:

P35348

Molecular weight:

51486.0

References

1. Stam WB, Van der Graaf PH, Saxena PR: Analysis of alpha 1L-adrenoceptor pharmacology in rat small mesenteric artery. Br J Pharmacol. 1999 Jun;127(3):661-70. [PubMed:10401556 ]
2. Michel MC, Hanft G, Gross G: Functional studies on alpha 1-adrenoceptor subtypes mediating inotropic effects in rat right ventricle. Br J Pharmacol. 1994 Feb;111(2):539-46. [PubMed:7911719 ]
3. Yu Y, Koss MC: Functional characterization of alpha-adrenoceptors mediating pupillary dilation in rats. Eur J Pharmacol. 2003 Jun 20;471(2):135-40. [PubMed:12818701 ]
4. Salles J, Gascon S, Badia A: Sustained increase in rat myocardial alpha 1A-adrenoceptors induced by 6-hydroxydopamine treatment involves a decelerated receptor turnover. Naunyn Schmiedebergs Arch Pharmacol. 1996 Mar;353(4):408-16. [PubMed:8935707 ]
5. Suzuki E, Tsujimoto G, Tamura K, Hashimoto K: Two pharmacologically distinct alpha 1-adrenoceptor subtypes in the contraction of rabbit aorta: each subtype couples with a different Ca2+ signalling mechanism and plays a different physiological role. Mol Pharmacol. 1990 Nov;38(5):725-36. [PubMed:1978244 ]

General function:

Involved in G-protein coupled receptor protein signaling pathway

Specific function:

Alpha-2 adrenergic receptors mediate the catecholamine- induced inhibition of adenylate cyclase through the action of G proteins

Gene Name:

ADRA2C

Uniprot ID:

P18825

Molecular weight:

49521.6

References

1. Frang H, Cockcroft V, Karskela T, Scheinin M, Marjamaki A: Phenoxybenzamine binding reveals the helical orientation of the third transmembrane domain of adrenergic receptors. J Biol Chem. 2001 Aug 17;276(33):31279-84. Epub 2001 Jun 6. [PubMed:11395517 ]

Transporters

General function:

Involved in ion transmembrane transporter activity

Specific function:

Translocates a broad array of organic cations with various structures and molecular weights including the model compounds 1-methyl-4-phenylpyridinium (MPP), tetraethylammonium (TEA), N-1-methylnicotinamide (NMN), 4-(4-(dimethylamino)styryl)- N-methylpyridinium (ASP), the endogenous compounds choline, guanidine, histamine, epinephrine, adrenaline, noradrenaline and dopamine, and the drugs quinine, and metformin. The transport of organic cations is inhibited by a broad array of compounds like tetramethylammonium (TMA), cocaine, lidocaine, NMDA receptor antagonists, atropine, prazosin, cimetidine, TEA and NMN, guanidine, cimetidine, choline, procainamide, quinine, tetrabutylammonium, and tetrapentylammonium. Translocates organic cations in an electrogenic and pH-independent manner. Translocates organic cations across the plasma membrane in both directions. Transports the polyamines spermine and spermidine. Transports pramipexole across the basolateral membrane of the proximal tubular epithelial cells. The choline transport is activated by MMTS. Regulated by various intracellular signaling pathways including inhibition by protein kinase A activation, and endogenously activation by the calmodulin complex, the calmodulin- dependent kinase II and LCK tyrosine kinase

Gene Name:

SLC22A1

Uniprot ID:

O15245

Molecular weight:

61187.4

References

1. Hayer-Zillgen M, Bruss M, Bonisch H: Expression and pharmacological profile of the human organic cation transporters hOCT1, hOCT2 and hOCT3. Br J Pharmacol. 2002 Jul;136(6):829-36. [PubMed:12110607 ]

General function:

Involved in ion transmembrane transporter activity

Specific function:

Mediates tubular uptake of organic compounds from circulation. Mediates the influx of agmatine, dopamine, noradrenaline (norepinephrine), serotonin, choline, famotidine, ranitidine, histamin, creatinine, amantadine, memantine, acriflavine, 4-[4-(dimethylamino)-styryl]-N-methylpyridinium ASP, amiloride, metformin, N-1-methylnicotinamide (NMN), tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, cisplatin and oxaliplatin. Cisplatin may develop a nephrotoxic action. Transport of creatinine is inhibited by fluoroquinolones such as DX-619 and LVFX. This transporter is a major determinant of the anticancer activity of oxaliplatin and may contribute to antitumor specificity

Gene Name:

SLC22A2

Uniprot ID:

O15244

Molecular weight:

62564.0

References

1. Hayer-Zillgen M, Bruss M, Bonisch H: Expression and pharmacological profile of the human organic cation transporters hOCT1, hOCT2 and hOCT3. Br J Pharmacol. 2002 Jul;136(6):829-36. [PubMed:12110607 ]
2. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235 ]

General function:

Involved in transmembrane transport

Specific function:

Mediates potential-dependent transport of a variety of organic cations. May play a significant role in the disposition of cationic neurotoxins and neurotransmitters in the brain

Gene Name:

SLC22A3

Uniprot ID:

O75751

Molecular weight:

61279.5

References

1. Hayer-Zillgen M, Bruss M, Bonisch H: Expression and pharmacological profile of the human organic cation transporters hOCT1, hOCT2 and hOCT3. Br J Pharmacol. 2002 Jul;136(6):829-36. [PubMed:12110607 ]

PMID: 22791293

Last updated on

Reverse transcriptase

View All Posts