DT-Web

DB00692 - Phentolamine


Identification
Name Phentolamine
Accession Number DB00692 (APRD00615)
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. [PubChem]
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 281.3523
Groups approved
Monoisotopic Weight 281.152812245
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.
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 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 ?-adrenergic receptors and produces a positive inotropic and chronotropic effect on the heart and increases cardiac output.
Absorption Not Available
Protein binding Not Available
Biotransformation Not Available
Route of elimination 10-13% of the drug is excreted unchanged in urine, and the fate of the remainder of the drug is unknown.
Toxicity Not Available
Affected organisms
  • Humans and other mammals
Interactions
Drug Interactions
Drug Mechanism of interaction
Tadalafil Tadalafil may enhance the hypotensive effect of Phentolamine. Monitor for hypotension during concomitant therapy.
Tamsulosin Concomitant use of alpha1-adrenergic antagonists, Tamsulosin and Phentolamine, may result in additive antihypertensive effects. Combination therapy is not recommended.
Treprostinil Additive hypotensive effect. Monitor antihypertensive therapy during concomitant use.
Vardenafil Additive hypotensive effects of the PDE5 inhibitor, Vardenafil, and alpha1-blocker, Phentolamine, may occur. Monitor for hypotension during concomitant therapy.
Food Interactions Not Available

Targets


Alpha-2A adrenergic receptor
Name Alpha-2A adrenergic receptor
Gene Name ADRA2A
Pharmacological action yes
Actions antagonist
References
  • Polak J, Moro C, Klimcakova E, Hejnova J, Majercik M, Viguerie N, Langin D, Lafontan M, Stich V, Berlan M: Dynamic strength training improves insulin sensitivity and functional balance between adrenergic alpha 2A and beta pathways in subcutaneous adipose tissue of obese subjects. Diabetologia. 2005 Dec;48(12):2631-40. Epub 2005 Nov 5. - Pubmed
  • 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. - Pubmed
  • 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. - Pubmed
  • 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. - Pubmed
  • 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. - Pubmed
  • 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. - Pubmed
  • Bylund DB: Subtypes of alpha 1- and alpha 2-adrenergic receptors. FASEB J. 1992 Feb 1;6(3):832-9. - Pubmed
  • 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. - Pubmed
DTHybrid score 0.3178
Alpha-1A adrenergic receptor
Name Alpha-1A adrenergic receptor
Gene Name ADRA1A
Pharmacological action yes
Actions antagonist
References
  • 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. - Pubmed
  • Bylund DB: Subtypes of alpha 1- and alpha 2-adrenergic receptors. FASEB J. 1992 Feb 1;6(3):832-9. - Pubmed
  • 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. - Pubmed
DTHybrid score 0.3558

Predictions


Id Partner name Gene Name Score
632 Alpha-1B adrenergic receptor ADRA1B 0.1048
629 Alpha-2B adrenergic receptor ADRA2B 0.079
378 Alpha-2C adrenergic receptor ADRA2C 0.0777
502 5-hydroxytryptamine 2A receptor HTR2A 0.0687
23 D(1A) dopamine receptor DRD1 0.0667
4119 Cytochrome P450 2D6 CYP2D6 0.0654
789 Alpha-1D adrenergic receptor ADRA1D 0.0632
831 D(2) dopamine receptor DRD2 0.0602
4512 Cytochrome P450 3A4 CYP3A4 0.0584
540 Sodium-dependent noradrenaline transporter SLC6A2 0.0519
320 5-hydroxytryptamine 1A receptor HTR1A 0.0484
4200 Cytochrome P450 1A2 CYP1A2 0.0451
492 Histamine H1 receptor HRH1 0.0448
590 5-hydroxytryptamine 2C receptor HTR2C 0.0407
766 Beta-2 adrenergic receptor ADRB2 0.038
131 Synaptic vesicular amine transporter SLC18A2 0.0361
1588 Multidrug resistance protein 1 ABCB1 0.0355
193 Beta-1 adrenergic receptor ADRB1 0.0336
824 Sodium-dependent serotonin transporter SLC6A4 0.0315
725 5-hydroxytryptamine 1D receptor HTR1D 0.031
163 D(1B) dopamine receptor DRD5 0.0308
432 D(4) dopamine receptor DRD4 0.0295
638 D(3) dopamine receptor DRD3 0.0281
713 Sodium-dependent dopamine transporter SLC6A3 0.0278
885 5-hydroxytryptamine 1B receptor HTR1B 0.0277
103 Muscarinic acetylcholine receptor M1 CHRM1 0.023
3941 Amine oxidase [flavin-containing] A MAOA 0.0226
716 5-hydroxytryptamine 7 receptor HTR7 0.0224
436 5-hydroxytryptamine 2B receptor HTR2B 0.0194
1181 Alpha-1-acid glycoprotein 1 ORM1 0.0189
274 Muscarinic acetylcholine receptor M5 CHRM5 0.0183
450 Muscarinic acetylcholine receptor M4 CHRM4 0.0178
6145 Solute carrier family 22 member 1 SLC22A1 0.0165
51 Muscarinic acetylcholine receptor M3 CHRM3 0.0159
617 Muscarinic acetylcholine receptor M2 CHRM2 0.0155
6016 Cytochrome P450 2C19 CYP2C19 0.0152
4757 Cytochrome P450 2C9 CYP2C9 0.0141
1256 5-hydroxytryptamine 6 receptor HTR6 0.0136
4118 Cytochrome P450 3A5 CYP3A5 0.0134
6030 Cytochrome P450 2B6 CYP2B6 0.013
6013 Cytochrome P450 2E1 CYP2E1 0.0126
3923 Cholinesterase BCHE 0.0122
101 Potassium voltage-gated channel subfamily H member 2 KCNH2 0.0122
6147 Solute carrier family 22 member 3 SLC22A3 0.012
6144 Solute carrier family 22 member 2 SLC22A2 0.011
828 Phenylalanine-4-hydroxylase PAH 0.0104
3109 Phenylalanine-4-hydroxylase phhA 0.0104
1539 Oligopeptide transporter, small intestine isoform SLC15A1 0.0101
6107 Cytochrome P450 3A7 CYP3A7 0.0097
1517 Beta-3 adrenergic receptor ADRB3 0.0095
341 5-hydroxytryptamine 3 receptor HTR3A 0.0087
872 Gamma-aminobutyric-acid receptor subunit alpha-1 GABRA1 0.0086
3426 Glutamine synthetase glnA 0.0084
3987 Glutamine synthetase GLUL 0.0084
3810 Catechol O-methyltransferase COMT 0.0083
124 Histamine H2 receptor HRH2 0.0083
528 5-hydroxytryptamine 1E receptor HTR1E 0.0083
3939 Amine oxidase [flavin-containing] B MAOB 0.0083
465 Calmodulin CALM1 0.0081
118 Organic cation/carnitine transporter 2 SLC22A5 0.0079
514 Potassium voltage-gated channel subfamily H member 6 KCNH6 0.0078
772 Potassium voltage-gated channel subfamily H member 7 KCNH7 0.0078
587 Serum albumin ALB 0.0076
1632 Solute carrier organic anion transporter family member 2B1 SLCO2B1 0.0076
6070 Nischarin NISCH 0.0075
6024 Cytochrome P450 1A1 CYP1A1 0.0074
3876 Aromatic-L-amino-acid decarboxylase DDC 0.0071
709 ATP-sensitive inward rectifier potassium channel 1 KCNJ1 0.0068
734 D1 dopamine receptor-interacting protein calcyon CALY 0.0067
4120 NADPH--cytochrome P450 reductase POR 0.0067
1636 Trace amine-associated receptor 1 TAAR1 0.0066
6020 Aldehyde oxidase AOX1 0.0062
6025 UDP-glucuronosyltransferase 1-4 UGT1A4 0.0055
4924 Cytochrome P450 2C8 CYP2C8 0.0044
6138 Multidrug resistance protein 3 ABCB4 0.0043
6164 POU domain, class 5, transcription factor 1 POU5F1 0.0042
1656 CYP2B protein CYP2B 0.0038
6859 Protein S100-A4 S100A4 0.0035
474 Acetylcholinesterase ACHE 0.0032
696 Kappa-type opioid receptor OPRK1 0.0031
233 Potassium channel subfamily K member 2 KCNK2 0.0031
4110 Voltage-dependent L-type calcium channel subunit beta-2 CACNB2 0.0029
4115 Voltage-dependent L-type calcium channel subunit alpha-1D CACNA1D 0.0029
833 Organic cation/carnitine transporter 1 SLC22A4 0.0029
6151 Monocarboxylate transporter 10 SLC16A10 0.0028
478 Voltage-dependent L-type calcium channel subunit alpha-1C CACNA1C 0.0028
3947 Xanthine dehydrogenase/oxidase XDH 0.0028
6098 Potassium voltage-gated channel subfamily D member 2 KCND2 0.0027
6099 Potassium voltage-gated channel subfamily D member 3 KCND3 0.0027
6101 Dimethylaniline monooxygenase [N-oxide-forming] 3 FMO3 0.0027
4112 Voltage-dependent L-type calcium channel subunit beta-4 CACNB4 0.0026
4114 Voltage-dependent L-type calcium channel subunit beta-3 CACNB3 0.0026
6178 UDP-glucuronosyltransferase 2B7 UGT2B7 0.0024
4113 Voltage-dependent L-type calcium channel subunit alpha-1F CACNA1F 0.0024
333 Voltage-dependent L-type calcium channel subunit beta-1 CACNB1 0.0024
1561 Troponin C, slow skeletal and cardiac muscles TNNC1 0.0024
6100 BDNF/NT-3 growth factors receptor NTRK2 0.0024
158 Sodium channel protein type 1 subunit alpha SCN1A 0.0023
4111 Voltage-dependent L-type calcium channel subunit alpha-1S CACNA1S 0.002
1374 Natriuretic peptides B NPPB 0.0019
1827 Gap junction alpha-1 protein GJA1 0.0019
1908 Vascular cell adhesion protein 1 VCAM1 0.0019
1618 High affinity nerve growth factor receptor NTRK1 0.0019
1086 Potassium voltage-gated channel subfamily KQT member 2 KCNQ2 0.0018
6432 Transporter snf 0.0018
164 Histamine H4 receptor HRH4 0.0017
194 NADH dehydrogenase [ubiquinone] 1 subunit C2 NDUFC2 0.0016
858 Potassium voltage-gated channel subfamily A member 1 KCNA1 0.0014
183 Vascular endothelial growth factor A VEGFA 0.0014
20 Prostaglandin G/H synthase 1 PTGS1 0.0014
5718 Cytochrome P450 2A6 CYP2A6 0.0013
6106 Cytochrome P450 2C18 CYP2C18 0.0012
1360 Sphingomyelin phosphodiesterase SMPD1 0.0012
467 Delta-type opioid receptor OPRD1 0.0012
6047 Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1A PDE1A 0.0011
1732 ATP-binding cassette sub-family G member 2 ABCG2 0.0011
5692 Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1B PDE1B 0.0011
776 Bile salt export pump ABCB11 0.001
1898 Cytochrome P450 1B1 CYP1B1 0.001
762 Voltage-dependent calcium channel subunit alpha-2/delta-1 CACNA2D1 0.0008
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