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__NOTOC__
{{Drugbox
{{drugbox
| Verifiedfields = changed
| IUPAC_name = 3-[4,5-dihydro-1''H''-imidazol-2-ylmethyl- (4-methylphenyl)-amino]phenol
| verifiedrevid = 464200826
| image = Phentolamine_svg.png
| IUPAC_name = 3-[(4,5-dihydro-1''H''-imidazol-2-ylmethyl)(4-methylphenyl)amino]phenol
| image = Phentolamine Structural Formulae.png
| image2 = Phentolamine-space-filling.png
 
<!--Clinical data-->
| tradename = Regitine
| Drugs.com = {{drugs.com|CONS|phentolamine}}
| pregnancy_category = C <small>([[U.S.]])</small>
| legal_status = 
| routes_of_administration = Usually IV or IM
 
<!--Pharmacokinetic data-->
| bioavailability = 
| protein_bound = 
| metabolism = Hepatic
| elimination_half-life = 19 minutes
 
<!--Identifiers-->
| CASNo_Ref = {{cascite|correct|CAS}}
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 50-60-2
| CAS_number = 50-60-2
| ATC_prefix = C04
| ATC_prefix = C04
| ATC_suffix = AB01
| ATC_suffix = AB01
| ATC_supplemental = {{ATC|G04|BE05}}
| ATC_supplemental = {{ATC|V03|AB36}}
| PubChem = 5775
| PubChem = 5775
| DrugBank = APRD00615
| IUPHAR_ligand = 502
| C = 17 | H = 19 | N = 3 | O = 1
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB00692
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 5571
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = Z468598HBV
| ChEBI_Ref = {{ebicite|changed|EBI}}
| ChEBI = 8081
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D08362
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 597
 
<!--Chemical data-->
| C=17 | H=19 | N=3 | O=1  
| molecular_weight = 281.352 g/mol
| molecular_weight = 281.352 g/mol
| bioavailability =  
| smiles = Oc3cc(N(c1ccc(cc1)C)CC/2=N/CCN\2)ccc3
| protein_bound =  
| InChI = 1/C17H19N3O/c1-13-5-7-14(8-6-13)20(12-17-18-9-10-19-17)15-3-2-4-16(21)11-15/h2-8,11,21H,9-10,12H2,1H3,(H,18,19)
| metabolism = Hepatic
| InChIKey = MRBDMNSDAVCSSF-UHFFFAOYAI
| elimination_half-life = 19 minutes
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| pregnancy_category = C <small>(U.S.)
| StdInChI = 1S/C17H19N3O/c1-13-5-7-14(8-6-13)20(12-17-18-9-10-19-17)15-3-2-4-16(21)11-15/h2-8,11,21H,9-10,12H2,1H3,(H,18,19)
</small>
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| legal_status =  
| StdInChIKey = MRBDMNSDAVCSSF-UHFFFAOYSA-N
| routes_of_administration = Usually IV or IM
}}
}}
{{SI}}
'''Phentolamine''' (Regitine) is a reversible<ref name="isbn0-7817-4266-8">{{cite book |author=Jewell, John R.; Longworth, David L.; Stoller, James K.; Casey, David |title=The Cleveland Clinic internal medicine case reviews |publisher=Lippincott Williams & Wilkins |location=Hagerstown, MD |year=2003 |isbn=0-7817-4266-8 |oclc= |doi= |accessdate= |page=32}}</ref> nonselective alpha-[[adrenergic antagonist]].<ref>{{MeshName|Phentolamine}}</ref>
{{CMG}}
 
==Mechanism==
Its primary action is [[vasodilation]] due to α<sub>1</sub> blockade.<ref>Brock G. Oral phentolamine (Vasomax). ''Drugs Today (Barcelona)''. 2000 Feb-Mar;36(2-3):121-4.</ref>


{{Editor Join}}
It also can lead to reflex [[tachycardia]] because of [[hypotension]] and α<sub>2</sub> inhibition, which increases sympathetic tone.<ref name=pharmnemonics>{{Cite book | author=Shen, Howard | title=Illustrated Pharmacology Memory Cards: PharMnemonics | year=2008 | publisher=Minireview | isbn=1-59541-101-1 | page=14}}</ref>


==Overview==
==Uses==
The primary application for phentolamine is for the control of [[hypertensive emergency|hypertensive emergencies]], most notably due to [[pheochromocytoma]]. <ref>Tuncel M, Ram VC. Hypertensive emergencies. Etiology and management. ''American Journal of Cardiovascular Drugs''. 2003;3(1):21-31.</ref>


'''Phentolamine''' (Regitine) is a reversible nonselective alpha-[[adrenergic]] [[antagonist]]. Its primary action is [[vasodilation]]. The primary application for phentolamine is for the control of [[hypertensive emergency|hypertensive emergencies]], most notably due to phaeochromocytoma ([[pheochromocytoma]]). It also has usefulness in  the treatment of [[cocaine]] induced hypertension, where one would generally avoid [[beta blockers]] and where [[calcium channel blockers]] are not effective. In this context it is probably most safely given by infusion since [[Bolus (medicine)|bolus]] doses have a propensity towards causing precipitous falls in blood pressure.
It also has usefulness in  the treatment of [[cocaine]]-induced cardiovascular complications, where one would generally avoid [[Beta-blocker]]s (e.g. [[metoprolol]]), as they can cause unopposed alpha-adrenergic mediated [[Coronary vasospasm|coronary vasoconstriction]], worsening myocardial ischemia and hypertension. It is important to note that phentolamine is not a first-line agent for this indication. Phentolamine should only be given to patients who do not fully respond to [[benzodiazepines]], [[nitroglycerin]], and [[calcium channel blockers]]. <ref>Hollander JE, Henry TD. Evaluation and management of the patient who has cocaine-associated chest pain. ''Cardiology Clinics''. 2006 Feb;24(1):103-14.</ref><ref>Chan GM, Sharma R, Price D, Hoffman RS, Nelson LS. Phentolamine Therapy for Cocaine-Association Acute Coronary Syndrome (CAACS). ''Journal of Medical Toxicology''. 2006 Sep;2(3):108-11.</ref>


When given by injection it causes blood vessels to expand, thereby increasing blood flow. When injected into the penis (intracavernosal), it increases blood flow to the penis, which results in an erection.
When given by injection it causes blood vessels to expand, thereby increasing blood flow. When injected into the penis (intracavernosal), it increases blood flow to the penis, which results in an erection.<ref>Bella AJ, Brock GB. Intracavernous pharmacotherapy for erectile dysfunction. ''Endocrine''. 2004 Mar-Apr;23(2-3):149-55.</ref>


It may be stored in [[crash cart]]s to counteract severe peripheral vasoconstriction secondary to [[extravasation]] of peripherally placed [[vasopressor]] infusions, typically of [[norepinephrine]]. [[Epinephrine]] infusions are less vasoconstrictive than norepinephrine as they primarily stimulate beta receptor more than alpha receptors, but the effect remains dose dependent.
It may be stored in [[crash cart]]s to counteract severe peripheral vasoconstriction secondary to [[extravasation]] of peripherally placed [[vasopressor]] infusions, typically of [[norepinephrine]]. [[Epinephrine]] infusions are less vasoconstrictive than norepinephrine as they primarily stimulate beta receptor more than alpha receptors, but the effect remains dose dependent.


Phentolamine also has diagnostic and therapeutic roles in [[complex regional pain syndrome]] (reflex sympathetic dystrophy).
Phentolamine also has diagnostic and therapeutic roles in [[complex regional pain syndrome]] (reflex sympathetic dystrophy).<ref>Rowbotham MC. Pharmacologic management of complex regional pain syndrome. ''Clinical Journal of Pain''. 2006 Jun;22(5):425-9.</ref>


Phentolamine has recently been introduced in the dental field as a local anesthetic reversal agent.  Distributed by Septodont, [[OraVerse]] is a Phentolamine Mesylate injection designed to reverse the local vasoconstrictor properties used in many local anesthetics to prolong anesthesia.<ref>http://www.novalar.com/oraverse-dental-specialty-pharmaceutical</ref>  OraVerse has been shown to accelerate the reversal of the lingering soft-tissue numbness associated with the widely used anesthetic-vasoconstrictor combinations.<ref>Malamed S. What's new in local anaesthesia? ''Society For The Advancement Of Anaesthesia In Dentistry Digest''. 2009 Jan;25:4-14.</ref>
==Chemistry==
Phentolamine can be synthesized by alkylation of 3-(4-methylanilino)phenol using 2-chloromethylimidazoline:<ref>K. Miescher, A. Marxer, E. Urech, {{US Patent|2503059}} (1950)</ref><ref>E. Urech, A. Marxer, K. Miescher, Helv. Chim. Acta, 33, 1386 (1950)</ref>
:[[File:Phentolamine synthesis.png|400px|left]]{{clear left}}
==References==
{{reflist|2}}


{{Antihypertensives and diuretics}}
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{{Urologicals}}
{{Drugs for erectile dysfunction and PE}}
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{{Alpha blockers}}


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Revision as of 02:02, 25 July 2014

Phentolamine
Clinical data
Trade namesRegitine
AHFS/Drugs.comMicromedex Detailed Consumer Information
Pregnancy
category
Routes of
administration		Usually IV or IM
ATC code
Pharmacokinetic data
MetabolismHepatic
Elimination half-life19 minutes
Identifiers
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
E number{{#property:P628}}
ECHA InfoCard{{#property:P2566}}Lua error in Module:EditAtWikidata at line 36: attempt to index field 'wikibase' (a nil value).
Chemical and physical data
FormulaC17H19N3O
Molar mass281.352 g/mol
3D model (JSmol)
 ☒N☑Y (what is this?)  (verify)

Phentolamine (Regitine) is a reversible[1] nonselective alpha-adrenergic antagonist.[2]

Mechanism

Its primary action is vasodilation due to α1 blockade.[3]

It also can lead to reflex tachycardia because of hypotension and α2 inhibition, which increases sympathetic tone.[4]

Uses

The primary application for phentolamine is for the control of hypertensive emergencies, most notably due to pheochromocytoma. [5]

It also has usefulness in the treatment of cocaine-induced cardiovascular complications, where one would generally avoid Beta-blockers (e.g. metoprolol), as they can cause unopposed alpha-adrenergic mediated coronary vasoconstriction, worsening myocardial ischemia and hypertension. It is important to note that phentolamine is not a first-line agent for this indication. Phentolamine should only be given to patients who do not fully respond to benzodiazepines, nitroglycerin, and calcium channel blockers. [6][7]

When given by injection it causes blood vessels to expand, thereby increasing blood flow. When injected into the penis (intracavernosal), it increases blood flow to the penis, which results in an erection.[8]

It may be stored in crash carts to counteract severe peripheral vasoconstriction secondary to extravasation of peripherally placed vasopressor infusions, typically of norepinephrine. Epinephrine infusions are less vasoconstrictive than norepinephrine as they primarily stimulate beta receptor more than alpha receptors, but the effect remains dose dependent.

Phentolamine also has diagnostic and therapeutic roles in complex regional pain syndrome (reflex sympathetic dystrophy).[9]

Phentolamine has recently been introduced in the dental field as a local anesthetic reversal agent. Distributed by Septodont, OraVerse is a Phentolamine Mesylate injection designed to reverse the local vasoconstrictor properties used in many local anesthetics to prolong anesthesia.[10] OraVerse has been shown to accelerate the reversal of the lingering soft-tissue numbness associated with the widely used anesthetic-vasoconstrictor combinations.[11]

Chemistry

Phentolamine can be synthesized by alkylation of 3-(4-methylanilino)phenol using 2-chloromethylimidazoline:[12][13]

File:Phentolamine synthesis.png

References

  1. ↑ Jewell, John R.; Longworth, David L.; Stoller, James K.; Casey, David (2003). The Cleveland Clinic internal medicine case reviews. Hagerstown, MD: Lippincott Williams & Wilkins. p. 32. ISBN 0-7817-4266-8.
  2. ↑ Phentolamine at the US National Library of Medicine Medical Subject Headings (MeSH)
  3. ↑ Brock G. Oral phentolamine (Vasomax). Drugs Today (Barcelona). 2000 Feb-Mar;36(2-3):121-4.
  4. ↑ Shen, Howard (2008). Illustrated Pharmacology Memory Cards: PharMnemonics. Minireview. p. 14. ISBN 1-59541-101-1.
  5. ↑ Tuncel M, Ram VC. Hypertensive emergencies. Etiology and management. American Journal of Cardiovascular Drugs. 2003;3(1):21-31.
  6. ↑ Hollander JE, Henry TD. Evaluation and management of the patient who has cocaine-associated chest pain. Cardiology Clinics. 2006 Feb;24(1):103-14.
  7. ↑ Chan GM, Sharma R, Price D, Hoffman RS, Nelson LS. Phentolamine Therapy for Cocaine-Association Acute Coronary Syndrome (CAACS). Journal of Medical Toxicology. 2006 Sep;2(3):108-11.
  8. ↑ Bella AJ, Brock GB. Intracavernous pharmacotherapy for erectile dysfunction. Endocrine. 2004 Mar-Apr;23(2-3):149-55.
  9. ↑ Rowbotham MC. Pharmacologic management of complex regional pain syndrome. Clinical Journal of Pain. 2006 Jun;22(5):425-9.
  10. ↑ http://www.novalar.com/oraverse-dental-specialty-pharmaceutical
  11. ↑ Malamed S. What's new in local anaesthesia? Society For The Advancement Of Anaesthesia In Dentistry Digest. 2009 Jan;25:4-14.
  12. ↑ K. Miescher, A. Marxer, E. Urech, Template:US Patent (1950)
  13. ↑ E. Urech, A. Marxer, K. Miescher, Helv. Chim. Acta, 33, 1386 (1950)

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