Potential Novel Therapies for Neurodevelopmental Diseases Targeting Oxidative Stress

Table 1

Antioxidant properties of N-acetylcysteine in neurodevelopmental disorders.

Authors	Model	Number of participants	Doses	Results
[86] (substance abuse)	Monkeys (Macaca mulatta)	5 young males	(i) 150 mg/kg/h, i.v. over 30 min and 12 mg/kg/h, i.v. over 9 hours	(i) May attenuate the decrease in dopamine transporters after methamphetamine adm.
[87] (propionic acid- (PPA-) induced biochemical autistic features)	Rats (western albino)	28 young males divided into 4 groups (control, PPA treated, NAC → PPA (protective), PPA → NAC (therapeutic))	2–250 mg/kg/day PPA 3 d; 3–50 mg/kg/day NAC 1 w → PPA 3 d; 4—toxic dose PPA → same dose NAC	(i) NAC successfully defied the oxidative stress induced by propionic acid administration
[88] (double-blind placebo-controlled schizophrenia patients (<60% medicated with clozapine)	Human	150	1000 mg bidaily (6 months)	(i) Improved negative symptoms, but the improvements were lost 1 month after the end of the trial; (ii) Side effect: gastrointestinal
[89] Double-blind (schizophrenia)	Human	11	2000 mg/day (oral) (8 weeks)	(i) Significant improvements regarding mismatch negativity and plasma glutathione concentration
[90] (treatment-resistant schizophrenia)	Human	1 female	600 mg/day (oral)+usual medication	↓ Positive and Negative Syndrome Scale (PANSS); ↓ Clinical Global Impression
[91] (randomized control trial, early psychosis)	Human	63 (32 NAC, 31 placebo)	2700 mg/day effervescent NAC (1800 mg in the morning, 900 evening, 6 months)	↑ by 23% brain GSH levels in the medial prefrontal cortex; (i) Improvement in positive symptoms, cognition, level auditory processing, and white matter diffusion
[92] (double-blind randomized controlled pilot trial, autism)	Human	33 (31 males, 2 females, ages 3.2-10.7 years)	900 mg/day (4 weeks) → 900 mg/twice per day (4 weeks) → 900 mg/thrice per day (4 weeks) (oral)	(i) NAC groups presented significant improvements on ABC-irritability subscale; (ii) Side effect: gastrointestinal
[93] (randomized placebo-controlled trial, autism)	Human	31 in the beginning (NAC 16, placebo 15—3 lost to follow-up, 3 left the trial) (4-12 years)	(i) Doses ranging from 33.6 to 64.3 mg/kg (12 weeks)	(i) GSH level significantly higher in the NAC group (), increased glutathione disulfide (); (ii) No significant impact on social impairment