QuickView for Phentolamine (compound)

Summary
General Info

PubChem

PubChem Compound 5775

Name:	Phentolamine
PubChem Compound ID:	5775
Description:	A nonselective alpha-adrenergic antagonist. It is used in the treatment of hypertension and hypertensive emergencies, pheochromocytoma, vasospasm of RAYNAUD DISEASE and frostbite, clonidine withdrawal syndrome, impotence, and peripheral vascular disease.
Molecular formula:	C₁₇H₁₉N₃O
Molecular weight:	281.352 g/mol
Synonyms:	Phentolaminum [INN-Latin]; C 7337; BRN 0272944; 2-((N-(m-Hydroxyphenyl)-p-toluidino)methyl)-2-imidazoline; 2-(N'-p-Tolyl-N'-m-hydroxyphenylaminomethyl)-2-imidazoline; Phenol, 3-[[(4,5-dihydro-1H-imidazol-2-yl)methyl](4-methylphenyl)amino]-; Dibasin; KBio2_003045; Spectrum4_000899; KBio2_000477. show more » Phentolaminum [INN-Latin]; C 7337; BRN 0272944; 2-((N-(m-Hydroxyphenyl)-p-toluidino)methyl)-2-imidazoline; 2-(N'-p-Tolyl-N'-m-hydroxyphenylaminomethyl)-2-imidazoline; Phenol, 3-[[(4,5-dihydro-1H-imidazol-2-yl)methyl](4-methylphenyl)amino]-; Dibasin; KBio2_003045; Spectrum4_000899; KBio2_000477; NINDS_000807; Regitine; Phenol, m-(N-(2-imidazolin-2-ylmethyl)-p-toluidino)-; KBioSS_000477; SPBio_002200; SMR000058051; KBio1_000807; Prestwick1_000230; Fentolamin; 2-(m-Hydroxy-N-p-tolylanilinomethyl)-2-imidazoline; EINECS 200-053-1; 2-(N-(m-Hydroxyphenyl)-p-toluidinomethyl)imidazoline; Prestwick0_000230; KBio3_001716; Phenol, 3-(((4,5-dihydro-1H-imidazol-2-yl)methyl)(4-methylphenyl)amino)-; 65-28-1; Spectrum3_000788; Trental; NCGC00016311-01; KBio2_005613; Regitin; Spectrum_000077; HSDB 3382; MLS000040874; 2-Imidazoline, 2-((N-(m-hydroxyphenyl)-p-toluidino)methyl)-; 73-05-2; nchembio705-6; 50-60-2; CAS-73-05-2; DivK1c_000807; Pentoxifyllin; KBioGR_001338; Phentolamine; 5-25-09-00365 (Beilstein Handbook Reference); C 7337 Ciba; Fentolamina [INN-Spanish] show less «

DrugBank

Identification

Name:	Phentolamine
Name (isomeric):	DB00692
Drug Type:	small molecule
Description:	A nonselective alpha-adrenergic antagonist. It is used in the treatment of hypertension and hypertensive emergencies, pheochromocytoma, vasospasm of RAYNAUD DISEASE and frostbite, clonidine withdrawal syndrome, impotence, and peripheral vascular disease.
Brand:	Regitin Methanesulphonate, Phentolamine Mesylate [USAN], Phentolamine Methanesulphonate, Phenotolamine, Regitine Mesylate, Phentolamine Mesilate, Regitine Methanesulfonate, Phentalamine, Regitin, Regitine, Phentolamine Mesylate, Regitipe, Phentolamine Methanesulfonate, Phentolamine, Methyl Sulfonate, Rogitine
Category:	Sympatholytics, Adrenergic alpha-Antagonists, Antihypertensive Agents
CAS number:	50-60-2

Pharmacology

Indication:	Used as an aid for the diagnosis of pheochromocytoma, and may be administered immediately prior to or during pheochromocytomectomy to prevent or control paroxysmal hypertension resulting from anesthesia, stress, or operative manipulation of the tumor. Phentolamine has also been used to treat hypertensive crisis caused by sympathomimetic amines or catecholamine excess by certain foods or drugs in patients taking MAO inhibitors, or by clonidine withdrawal syndrome. Other indications include the prevention of dermal necrosis and sloughing following IV administration or extravasation of norepinephrine, decrease in impedance to left ventricular ejection and the infarct size in patients with MI associated with left ventricular failure, treatment of erectile dysfunction through self-injection of small doses combined with papaverine hydrochloride into the corpus cavernosum, and as an adjunct to the management of cocaine overdose to reverse coronary vasoconstriction following use of oxygen, benzodiazepines,and nitroglycerin.
Pharmacology:	Phentolamine is indicated for the control of episodes of hypertension and sweating that occur with a disease called pheochromocytoma. If tachycardia is excessive, it may be necessary to use a beta-blocking agent concomitantly. Phentolamine is a long-acting, adrenergic, alpha-receptor blocking agent which can produce and maintain "chemical sympathec... show more » Phentolamine is indicated for the control of episodes of hypertension and sweating that occur with a disease called pheochromocytoma. If tachycardia is excessive, it may be necessary to use a beta-blocking agent concomitantly. Phentolamine is a long-acting, adrenergic, alpha-receptor blocking agent which can produce and maintain "chemical sympathectomy" by oral administration. It increases blood flow to the skin, mucosa and abdominal viscera, and lowers both supine and erect blood pressures. It has no effect on the parasympathetic system. Phentolamine works by blocking alpha receptors in certain parts of the body. Alpha receptors are present in the muscle that lines the walls of blood vessels. When the receptors are blocked by Phentolamine, the muscle relaxes and the blood vessels widen. This widening of the blood vessels results in a lowering of blood pressure. show less «
Mechanism of Action:	Phentolamine produces its therapeutic actions by competitively blocking alpha-adrenergic receptors (primarily excitatory responses of smooth muscle and exocrine glands), leading to a muscle relaxation and a widening of the blood vessels. This widening of the blood vessels results in a lowering of blood pressure. The action of phentolamine on the al... show more » Phentolamine produces its therapeutic actions by competitively blocking alpha-adrenergic receptors (primarily excitatory responses of smooth muscle and exocrine glands), leading to a muscle relaxation and a widening of the blood vessels. This widening of the blood vessels results in a lowering of blood pressure. The action of phentolamine on the alpha adrenergic receptors is relatively transient and the blocking effect is incomplete. The drug is more effective in antagonizing responses to circulating epinephrine and/or norepinephrine than in antagonizing responses to mediator released at the adrenergic nerve ending. Phentolamine also stimulates β-adrenergic receptors and produces a positive inotropic and chronotropic effect on the heart and increases cardiac output. show less «
Route of elimination:	10-13% of the drug is excreted unchanged in urine, and the fate of the remainder of the drug is unknown.
Half Life:	19 minutes
Affected organisms:	Humans and other mammals

Interactions

Drug interaction:

Tadalafil	Tadalafil may enhance the hypotensive effect of Phentolamine. Monitor for hypotension during concomitant therapy.
Vardenafil	Additive hypotensive effects of the PDE5 inhibitor, Vardenafil, and alpha1-blocker, Phentolamine, may occur. Monitor for hypotension during concomitant therapy.
Treprostinil	Additive hypotensive effect. Monitor antihypertensive therapy during concomitant use.
Tamsulosin	Concomitant use of alpha1-adrenergic antagonists, Tamsulosin and Phentolamine, may result in additive antihypertensive effects. Combination therapy is not recommended.

Targets

Alpha-2A adrenergic receptor

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

UniProt ID:

P08913

Gene:

ADRA2A

Actions:

antagonist

References:

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Molderings GJ, Bonisch H, Bruss M, Likungu J, Gothert M: Species-specific pharmacological properties of human alpha(2A)-adrenoceptors. Hypertension. 2000 Sep;36(3):405-10.
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Vonend O, Habbel S, Stegbauer J, Roth J, Hein L, Rump LC: Alpha(2A)-adrenoceptors regulate sympathetic transmitter release in mice kidneys. Br J Pharmacol. 2007 Jan;150(1):121-7. Epub 2006 Nov 20.
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Trendelenburg AU, Meyer A, Klebroff W, Guimaraes S, Starke K: Crosstalk between presynaptic angiotensin receptors, bradykinin receptors and alpha 2-autoreceptors in sympathetic neurons: a study in alpha 2-adrenoceptor-deficient mice. Br J Pharmacol. 2003 Apr;138(8):1389-402.
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Blandizzi C, Fornai M, Colucci R, Baschiera F, Barbara G, De Giorgio R, De Ponti F, Breschi MC, Del Tacca M: Altered prejunctional modulation of intestinal cholinergic and noradrenergic pathways by alpha2-adrenoceptors in the presence of experimental colitis. Br J Pharmacol. 2003 May;139(2):309-20.
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Giussani DA, Moore PJ, Bennet L, Spencer JA, Hanson MA: Alpha 1- and alpha 2-adrenoreceptor actions of phentolamine and prazosin on breathing movements in fetal sheep in utero. J Physiol. 1995 Jul 1;486 ( Pt 1):249-55.
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Bylund DB: Subtypes of alpha 1- and alpha 2-adrenergic receptors. FASEB J. 1992 Feb 1;6(3):832-9.
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Saeed M, Sommer O, Holtz J, Bassenge E: Alpha-adrenoceptor blockade by phentolamine causes beta-adrenergic vasodilation by increased catecholamine release due to presynaptic alpha-blockade. J Cardiovasc Pharmacol. 1982 Jan-Feb;4(1):44-52.
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Alpha-1A adrenergic receptor