Phenoxybenzamine-d5 (hydrochloride)

Phenoxybenzamine-d5 is intended for use as an internal standard for the quantification of phenoxybenzamine (Item No. 16211) by GC- or LC-MS. Phenoxybenzamine is an antagonist of ?-adrenergic receptors (?-ARs).{53203,26625} It inhibits norepinephrine-induced inositol phosphate formation in HEK293 cells expressing ?1-ARs (EC50s = 125.9-316.2 nM), as well as radioligand binding to ?2A-, ?2B-, and ?2C-ARs in CHO cell membranes (Kis = 60, 10, and 60 nM, respectively). Phenoxybenzamine (0.5-5 µM) decreases norepinephrine-, histamine-, and calcium-induced contractions in isolated rabbit aortic strips.{53204} It also inhibits proliferation of nine cancer cell lines, including lymphoma, breast, and lung cancer cells, with IC50 values ranging from 29.5 to 99.8 µM.{53205} Phenoxybenzamine (3-1,000 µg/kg) reduces increases in diastolic blood pressure induced by the ?-AR agonists cirazoline (Item No. 21791), St-587, Sgd 101/75, and B-HT 920 (Item No. 14177) in pithed rats.{53206} 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).{53207} Formulations containing phenoxybenzamine have been used in the treatment of hypertension and hyperhidrosis associated with pheochromocytomas, an adrenal medullary neuroendocrine tumor.