Disease relevance of docarpamine

• After 8 wk of docarpamine treatment, ascites disappeared completely in three of the five patients and decreased in the remainder [1].
• Cardiorenal effects of an orally active dopamine prodrug (TA-870) in patients with congestive heart failure [2].
• METHODS: We reviewed the records of 26 patients who had developed low cardiac output syndrome (LOS) after cardiac surgery and received docarpamine during the early postoperative course [3].
• Five patients discontinued docarpamine within 2 days due to arrhythmia [3].
• This study examined the effects of docarpamine on hemodynamics and evaluated its safety in 11 children undergoing open heart surgery for congenital heart disease [4].

High impact information on docarpamine

• To determine whether the GRK4 genotype is associated with impaired D1R function, we tested the natriuretic effect of docarpamine, a dopamine prodrug, in normotensive individuals with or without GRK4 polymorphisms (n = 18) [5].
• Dopamine (DA) levels in human plasma after oral administration of TA-870 and iv infusion of DA were measured by HPLC [6].
• The level of the total urinary metabolites (free and conjugated) after oral administration of TA-870 decreased as follows: DA greater than HVA greater than DOPAC greater than DEC-TA-870 [6].
• The pharmacokinetics of a dopamine derivative, TA-870, and dopamine (DA) after oral administration are compared in rats and dogs [7].
• The AUC values of free DA in plasma after oral administration of TA-870 (30 or 33.5 mg/kg) were 4-6 times higher than those after DA in both animal species [7].

Biological context of docarpamine

• Since sulfoconjugated dopamine is thought to be a possible precursor of active free dopamine in plasma, orally administered docarpamine might be stored as a reserve pool for free dopamine in patients who undergo cardiac surgery [8].
• Furthermore, at a lower dose of TA-870 (2 mg/kg), renal vascular resistance (RVR) decreased and renal blood flow (RBF) increased [9].
• When TA-870 (1 mg/kg) was injected in anesthetized dogs, renal vascular resistance was decreased and renal blood flow was increased [10].
• Hydrolysis of TA-870 with this immobilized carboxylesterase was a maximum at pH 7-8 and 50 degrees C, and the activity decreased in the presence of organic solvent such as acetonitrile [11].
• In conclusion, TA-870 increased myocardial contractility and output by the enteral route, and the latter effect was produced at lower doses with the help of peripheral vasodilation due to the activation of dopamine receptors [9].

Anatomical context of docarpamine

• Conversion rates from docarpamine to DA in various rat tissue homogenates were in the order of the liver > small intestine > blood [12].

Associations of docarpamine with other chemical compounds

• The main first pass metabolism after oral administration of docarpamine are catechol ester hydrolysis in the small intestine, and amide hydrolysis and conjugation in the liver [12].
• We concluded that TA-870 and DEC-TA-870 exert weak vasodilatory effects that are different from that of DA in vitro, and that TA-870 exerts its vasodilatory effect after its conversion to free DA in vivo [10].
• The docarpamine-induced changes in MAP and HR in both rat strains (n=5/strain) were blocked by the D1-like antagonist, SCH23390. alpha-Adrenergic (n=4) and vasopressin V1 (n=3) receptor blockade also abrogated the effects of docarpamine in WKY rats [13].
• The two drugs also produced similar decreases in renal vascular resistance (21.2 +/- 2.2 and 13.6 +/- 3.4%, respectively) and increases in renal blood flow (27.9 +/- 3.2 and 17.9 +/- 5.2%, respectively), however, the duration of renal vasodilation after docarpamine was longer than that of levodopa [14].

Gene context of docarpamine

• In conclusion, TA-870, when administered enterally to rats, produced the natriuretic effect via the DA1 dopamine receptor and positive inotropic effects via the beta 1 adrenergic receptor stimulation, and these effects were not attenuated by chronic treatment with TA-870 [15].

Analytical, diagnostic and therapeutic context of docarpamine

• We treated 10 cirrhotic patients with refractory ascites with docarpamine or placebo and the same dose of diuretics used before hospitalization [1].
• The plasma level of free deethoxycarbonylated TA-870 (DEC-TA-870) after oral administration of TA-870 was higher than that of DA [6].
• A new method for the high performance liquid chromatographic (HPLC) determination of N-(N-acetyl-L-methionyl)-O,O-bis(ethoxycarbonyl)dopamine (TA-870), a dopamine prodrug, in biological fluid has been developed [11].
• A single oral dose of TA-870 (1,200 mg) improved left ventricular fractional shortening and mean circumferential velocity on M-mode echocardiography (p less than 0.01 for both) [2].
• We studied the effects of bolus intravenous injection of the dopamine prodrug, docarpamine (200 microg/kg), on mean arterial pressure (MAP) and heart rate (HR) in Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHRs) [13].

References