Fenoldopam

Fenoldopam (76) is an antihypertensive renal vasodilator apparently operating through the dopamine system. It is conceptually similar to trepipam. Fenoldopam is superior to dopamine itself because of its oral activity and selectivity for dopamine D-1 receptors (D-2 receptors are as.sociated with emesis). It is synthesized by reduction of 3,4-dimethoxyphenylacetonitrile (70) to dimethoxyphenethylamine (71). Attack of diis last on 4-methoxystyrene oxide (72) leads to the product of attack on the epoxide on the less hindered side (73). Ring closure with strong acid leads to substituted benzazepine 74. O-Dealkylation is accomplished with boron tribromide and the catechol moiety is oxidized to the ortho-quinone 75. Treatment with 9NHC1 results in conjugate (1,6) chloride addition and the formation of fenoldopam (76) [20,21]. 

Activation of dopamine 1 receptors (fenoldopam) or inhibition of A1 adenosine receptors (CVT 124, KW-3902) are additional approaches that cause increased NaCl excretion at least in part by inhibition of proximal reabsoiption. 

C Hj 02 123-11-5) see Anisindione Diltiazem Fenoldopam mesilate Mepyramine Raloxifene hydrochloride m-anisidine... 

Acute renal failure/microangiopathic hemolytic anemia o Drugs of choice—nicardipine, fenoldopam... 

Fenoldopam mesylate 0.1-0.3 mcg/kg/minute as IV infusion11 Less than 5 minutes 30 minutes Tachycardia, headache, nausea, flushing Most hypertensive emergencies use with caution with glaucoma... 

Therapeutic measures that have been used to decrease the incidence of contrast-induced nephropathy include extracellular volume expansion, minimization of the amount of contrast administered, and treatment with oral acetylcysteine. Theophylline, fenoldopam, loop diuretics, mannitol, dopamine, and calcium antagonists have no effect or may worsen ARF. 

Fenoldopam does not decrease the incidence of contrast nephropathy.40 Due to its hypotensive effect, it may worsen kidney function. 

V-Ethyl carbamate esters of fenoldopam, used for treatment of acute circulatory failure, provide another example of a carbamate ester prodrug. The intrinsically short half-life and extensive first-pass metabolism of fenoldopam limit its oral administration. /V-Ethyl carbamate esters of fenoldopam provide elevated plasma fenoldopam levels and increases in the renal blood flow of significantly greater duration than when the parent compound is administered orally [30],... 

Fenoldopam ter of terbutaline bis-A,A-dimcthyl carbamate Carbamate ester, e.g., A-ethyl carbamate ester 18... 

D Brooks, PD Depalma, MJ Cyronak, MA Bryant, K Karpinski, B Mico, D Gaita-nopoulos, PA Chambers, KF Erhard, J Weinstock. The identification of fenoldopam prodrugs with prolonged renal vasodilator. J Pharmacol Exper Ther 254(3) 1084— 1089, 1990. 

Ophthalmic corticosteroids (high risk) Systemic corticosteroids Nasal/inhaled corticosteroids Fenoldopam... 

Many other strategies are popular but lack supportive evidence, including mannitol, loop diuretics, dopamine, and fenoldopam. 

Felodipine (Plendil) Fenofibrate (Tricor) Fenoldopam (Corlopam) Fenoterol (Berotec) Fentanyl (Duragesic)... 

Di-receptors (comprising subtypes Di and D5) and D2-receptors (comprising subtypes D2, D3, and D4). The aforementioned actions are mediated mainly by D2 receptors. When given by infusion, dopamine causes dilation of renal and splanchnic arteries. This effect is mediated by Di receptors and is utilized in the treatment of cardiovascular shock and hypertensive emergencies by infusion of dopamine and fenoldopam, respectively. At higher doses, Pi-adrenoceptors and, finally, a-receptors are activated, as evidenced by cardiac stimulation and vasoconstriction, respectively. 

Drugs for the control of hypertensive crises include nifedipine (capsule, to be chewed and swallowed), nitroglycerin (sublingually), clonidine (p.o. or i.v., p. 96), dihydralazine (i.v.), diazoxide (i.v.), fenoldopam (by infusion, p. 114) and sodium nitroprusside (p. 120, by infusion). The nonselective a-blocker phentolamine (p. 90) is indicated only in pheochromocytoma... 

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