N-Acetylcysteine amide: a derivative to fulfill the promises of N-Acetylcysteine

Abstract

In the present human health scenario, implication of oxidative stress in numerous pathologies including neurodegenerative, cardiovascular, liver, renal, pulmonary disorders, and cancer has gained attention. N-Acetylcysteine (NAC), a popular thiol antioxidant, has been clinically used to treat various pathophysiological disorders. However, NAC therapy is routine only in paracetamol intoxication and as a mucolytic agent. Over six decades, numerous studies involving NAC therapy have yielded inconsistent results, and this could be due to low bioavailability. In order to overcome the limitations of NAC, an amide derivative N-Acetylcysteine amide (NACA) has been synthesized to improve the lipophilicity, membrane permeability, and antioxidant property. Recent studies have demonstrated the blood-brain barrier permeability and therapeutic potentials of NACA in neurological disorders including Parkinson's disease, Alzheimer's disease, Multiple sclerosis, Tardive dyskinesia, and HIV-associated neurological disorders. In addition, NACA displays protective effect against pulmonary inflammation and antibiotic-induced apoptosis. Forthcoming research on the possible therapeutic properties of NACA and its generics in the management of pathologies associated with extracellular matrix degradation and oxidative stress-related inflammation is highly exiting. Superior bioavailability of NACA is likely to fulfill the promises of NAC as well as a molecule to improve the endurance and resident time of bioscaffolds and biomaterials. Till date, more than 800 reviews on NAC have been published. However, no comprehensive review is available on the therapeutic applications of NACA. Therefore, the current review would be the first to emphasize the therapeutic potentials of NACA and its derivatives.

Neuronal Glutathione Content and Antioxidant Capacity can be Normalized In Situ by N-acetyl Cysteine Concentrations Attained in Human Cerebrospinal Fluid

“…There is also a growing interest in the use of NAC to treat other neurological and psychiatric disorders in which oxidative stress has been implicated, including adrenoleukodystrophy, Alzheimer disease, schizophrenia, and compulsive disorders [15,16]. However, there has been uncertainty as to the extent that NAC can cross the human blood-brain barrier [17], with resulting uncertainty about doses required for a rational clinical trial.…”

Ursodeoxycholic Acid Attenuates Acute Aortic Dissection Formation in Angiotensin II-Infused Apolipoprotein E-Deficient Mice Associated with Reduced ROS and Increased Nrf2 Levels

“…Obviously, Ang II-induced increase of ROS was pretreatment with NAC, an effective ROS scavenger (Fig. 5A) [23]. Additionally, the ROS production induced by challenge of Ang II was comparable to the result of ROS stimulator H 2 O 2 ( Fig.…”

Neuroprotective effects of N-acetylcysteine amide on experimental focal penetrating brain injury in rats

“…NAC is also a potent free radical scavenger and antioxidant as a result of its nucleophilic reactions with ROS [12]. http Despite the many promising prospects, clinical trials in several diseases have failed [13], possibly attributed to a low (6-10%) bioavailability [14]. Therefore, NAC is in clinical use only for acetaminophen intoxication and as a mucolytic agent.…”