Description
Phenoxybenzamine-d
5 is intended for use as an internal standard for the quantification of phenoxybenzamine by GC- or LC-MS. Phenoxybenzamine is an antagonist of α-adrenergic receptors (α-ARs). It inhibits norepinephrine-induced inositol phosphate formation in HEK293 cells expressing α
1-ARs (EC
50s = 125.9-316.2 nM), as well as radioligand binding to α
2A-, α
2B-, and α
2C-ARs in CHO cell membranes (K
is = 60, 10, and 60 nM, respectively). Phenoxybenzamine (0.5-5 μM) decreases norepinephrine-, histamine-, and calcium-induced contractions in isolated rabbit aortic strips. It also inhibits proliferation of nine cancer cell lines, including lymphoma, breast, and lung cancer cells, with IC
50 values ranging from 29.5 to 99.8 μM. Phenoxybenzamine (3-1,000 μg/kg) reduces increases in diastolic blood pressure induced by the α-AR agonists cirazoline , St-587, Sgd 101/75, and B-HT 920 in pithed rats. It also decreases the time to find the platform in the Morris water maze, indicating restored spatial memory, in a rat model of fluid percussion-induced traumatic brain injury (TBI). Formulations containing phenoxybenzamine have been used in the treatment of hypertension and hyperhidrosis associated with pheochromocytomas, an adrenal medullary neuroendocrine tumor.
References
[1] K P MINNEMAN. Selectivity of agonists for cloned alpha 1-adrenergic receptor subtypes.[J]. Molecular Pharmacology, 1994, 46 5: 929-936.
[2] H. FRANG. Phenoxybenzamine Binding Reveals the Helical Orientation of the Third Transmembrane Domain of Adrenergic Receptors*[J]. The Journal of Biological Chemistry, 2001, 29 1: 31279-31284. DOI:
10.1074/jbc.m104167200[3] GRANT A. MCPHERSON Errol M Elena Krstew. EFFECTS OF PHENOXYBENZAMINE ON RESPONSES TO SOME RECEPTOR AGONISTS AND CALCIUM IN VITRO[J]. Clinical and Experimental Pharmacology and Physiology, 1985, 12 5: 455-464. DOI:
10.1111/j.1440-1681.1985.tb00895.x[4] INCHIOSA M A. Anti-tumor activity of phenoxybenzamine and its inhibition of histone deacetylases.[J]. ACS Applied Bio Materials, 2018: e0198514. DOI:
10.1371/journal.pone.0198514[5] P B TIMMERMANS. Effects of the irreversible alpha-adrenoceptor antagonists phenoxybenzamine and benextramine on the effectiveness of nifedipine in inhibiting alpha 1- and alpha 2-adrenoceptor mediated vasoconstriction in pithed rats.[J]. Naunyn-Schmiedeberg’s archives of pharmacology, 1985, 329 4: 404-413. DOI:
10.1007/bf00496376[6] THOMAS F RAU. Phenoxybenzamine is neuroprotective in a rat model of severe traumatic brain injury.[J]. International Journal of Molecular Sciences, 2014, 15 1: 1402-1417. DOI:
10.3390/ijms15011402
