We showed that adolescents with ADHD, who are found to have germline mutations impacting the GRM network, show clinical improvement using global improvement and severity scales as well as ADHD symptom scales in response to escalating dosages of NFC-1, a non-selective glutamate receptor activator with additional GABAB and cholinergic enhancing effects14. We observed no significant changes in CGI-S scores among any patients between enrollment and placebo week, thus precluding any withdrawal effects on the six subjects who had been treated with stimulants and the one subject treated with atomoxetine (Supplementary Table 4). This indicates that rebound effects, reported in stimulants...
...At baseline most subjects were rated as moderately to severely impaired (mean CGI-S 4.83), indicating that their ADHD symptoms were disruptive enough to be causing functional impairment. After 1 week of fixed placebo followed by 4 weeks of dose escalation from 50 mg BID to 400 mg BID, over 80% of subjects showed clinically significant improvement in ADHD symptoms with mean CGI-S score of 3.86, mildly to moderately impaired. Significant improvement was also observed in CGI-I scores as compared to placebo therapy...
Improvement increased as dose was increased, suggesting dosages starting at 100 mg BID (3–5 mg/kg per day) may be required for clinical response.
Discovering efficacious novel therapeutics for neuropsychiatric disorders has proven to be difficult in part because of a lack of clear understanding of their molecular etiologies65. Our group’s research in ADHD is focused on characterizing genetic variants that disrupt a specific pathway (the glutamatergic pathway) involving neurotransmission in the brain. We have identified a small molecule compound, NFC-1, which previously underwent extensive clinical testing66 and was shown to have stimulatory activity towards mGluR pathways67–69, producing notable psychoactive effects in animal models
NS-105 (10 mg/kg) showed the increase of ACh release from the cerebral cortex and the enhancement of HACU both in the cerebral cortex and hippocampus, but showed no change in activity of ChAT. NS-105 also reversed memory disruption induced by baclofen, a potent GABA(B) receptor agonist, but all of reference drugs did not. These results suggest that antiamnestic action of NS-105 is due to the facilitation of cholinergic neuronal activity and the suppression of GABA(B) receptor-mediated responses.
These findings suggest that the inhibitory action of NS-105 on adenylyl cyclase activity is mediated through group II and group III mGlu receptor subclasses while the facilitatory action is dependent on the group I mGlu receptor subclass.
ADHD is mainly attributed to high levels of cAMP. High levels of cAMP cause prefrontal cortex based symptoms, namely executive control, unable to inhibit emotions, focusing at all related to cAMP.
When Dopamine hits the D4 and D2 Dopamine receptors in the brain. They are supposed to activate and lower cAMP. In some people's genes, this doesn't decrease cAMP sufficiently. The result is overwhelming signal-noise. Like way too much static.
Fasoracetam may work by normalizing cAMP-levels and produce better focus, and it does it without the side effects of rapidly increasing Dopamine and it's associated side effects of which addiction is only one of many. e.g. Adderall.
Fasoracetam, also known as NS-105, NFC-1 and LAM-105 is a chemical that belongs to a class of drugs called racetams. Like the popular Piracetam, Fasoracetam is a nootropic, meaning it lies in in-between land between the land of supplements and drugs.
Originally developed in Japan by a company called Nippon Shinyaku for dementia. Fasoracetam failed at phase 3 clinical trials for dementia. The company had spent 200 million USD in development.
Recently, interest in Fasoracetam has come back by a company called Neurofix , now Aevi Genomic Medicine, which began clinical trials in 2016 in adolescents with ADHD, Autism or Anxiety.
Anyone who have mutations in the glutamate receptor gene.