Stereochemistry | ABSOLUTE |
Molecular Formula | C7H16N4O2 |
Molecular Weight | 188.2275 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 1 / 1 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CNC(=N)NCCC[C@H](N)C(O)=O
InChI
InChIKey=NTNWOCRCBQPEKQ-YFKPBYRVSA-N
InChI=1S/C7H16N4O2/c1-10-7(9)11-4-2-3-5(8)6(12)13/h5H,2-4,8H2,1H3,(H,12,13)(H3,9,10,11)/t5-/m0/s1
Molecular Formula | C7H16N4O2 |
Molecular Weight | 188.2275 |
Charge | 0 |
Count |
MOL RATIO
1 MOL RATIO (average) |
Stereochemistry | ABSOLUTE |
Additional Stereochemistry | No |
Defined Stereocenters | 1 / 1 |
E/Z Centers | 0 |
Optical Activity | UNSPECIFIED |
Tilarginine is L-N-monomethyl arginine (L -NMMA), a non-selective inhibitor of nitric oxide synthase (NOS), which has been studied in the treatment of septic shock and cardiogenic shock complicating myocardial infarction. Despite strong evidence that excessive nitric oxide (NO) production plays a pivotal role in the pathogenesis of septic shock and may contribute to the pathogenesis of cardiogenic shock complicating myocardial infarction, outcome studies in these two disorders have proved disappointing. Tilarginine therapy was associated with an excess mortality, particularly at doses > 5 mg/(kg h), in septic shock, whereas the effects of a lower dose (1 mg/(kg h)) in cardiogenic shock complicating myocardial infarction were neutral. The excess mortality in patients with septic shock was almost certainly the result of unfavorable hemodynamic changes induced by Tilarginine (decreased cardiac output, increased pulmonary vascular resistance and reduced tissue oxygen delivery) whereas the lack of benefit in patients with cardiogenic shock complicating myocardial infarction may have been because the dose of Tilarginine was too low.
Originator
Approval Year
Cmax
AUC
T1/2
PubMed
Patents
Sample Use Guides
Tilarginine was given as an intravenous infusion starting with a dose of 2.5 mg/(kg h), which could be subsequently increased in an incremental manner up to a maximum dose of 20 mg/(kg h).
Route of Administration:
Intravenous
L-NMMA (Tilarginine) was assayed for ability to inhibit NO production in human colorectal adenocarcinoma (DLD-1) cells preincubated with a cytokine cocktail. Cells were grown to confluence in 12-well plates. Cytokines or other agents were added to fresh media (1 mL/well). At 18-24-h postinduction, culture supernatants were harvested and stored at -20 C for nitrite analysis. Nitrite was measured spectrophotometrically using the Griess reagent