Ncarbamylglutamate

N-carbamylglutamate, also known as NCG or N-carbamyl-L-glutamic acid, is a synthetic structural analog of the natural urea cycle cofactor N-acetylglutamate (NAG). It functions as an allosteric activator of carbamoyl phosphate synthetase I (CPS1), the first enzyme in the urea cycle, thereby promoting the conversion of ammonia to urea.

Because CPS1 activity depends on NAG, NCG can substitute for deficient NAG in certain disorders and help reduce hyperammonemia. It is used to treat hyperammonemia associated with N-acetylglutamate synthase (NAGS) deficiency and may be considered as an adjunct in the management of other urea cycle disorders when ammonia levels remain elevated despite standard therapies. Regulatory approvals and indications vary by country, and the drug is marketed in some regions under brand names such as carglumic acid (Carbaglu).

Administration is oral and treatment is guided by clinical response, ammonia concentrations, and metabolic status. Dosing is individualized by age and weight and requires medical supervision. The pharmacokinetic profile is described in clinical guidelines rather than in universal dosing tables, with monitoring focusing on metabolic control and potential drug interactions.

Common adverse effects are generally mild and may include gastrointestinal symptoms such as nausea, vomiting, or diarrhea; hypersensitivity reactions are possible but rare. Long-term therapy requires regular follow-up to monitor ammonia levels, amino acid balance, liver function, and overall metabolic status.

See also: N-acetylglutamate, urea cycle disorders, CPS1.