What is Nebracetam?
Nebracetam (3-benzylaminomethyl-2-pyrrolidone, or WEB1881FU) is a lesser-studied member of the racetam family of nootropics. Like other racetams, it is an aminomethyl pyrrolidinone derivative of piracetam (the original nootropic). It was first synthesized in Germany in the late 1980s, where it was manufactured by Boehringer Ingelheim. It is licensed for use in Japan, but is no longer under development in Germany. Its proprietary name is Memolog. Applications for licensing have been filed in other countries. It is not currently available for purchase as a nutritional supplement.
How does it work?
It has direct cholinomimetic properties, which means that it mimics the actions of acetylcholine on presynaptic muscarinic receptors throughout the central nervous system, including the brain. Nebracetam also decreases dopamine and serotonin uptake from the synapse, meaning that these neurotransmitters are able to exert their effects for longer periods of time before they are recycled. This is similar to how many antidepressants work. This compound also modulates neuronal calcium. Nebracetam has also been demonstrated to increase neuronal firing in the hippocampus as well as cerebral blood flow.
Nebracetam has been investigated as a cognition-enhancing drug, but most of the studies have taken place in animal models. It has been shown to protect neurons in animals exposed to low levels of oxygen and low blood sugar. Nebracetam is also protective against glutamate toxicity, presumably via its modulation of calcium entry. In animal models of Alzheimer’s disease, nebracetam improved memory in a dose-dependent manner. It also protected against ischemia- (lack of oxygen) induced neuronal death in a rat model of stroke. The compound has also been tested as a possible antidepressant, presumably because its mechanism of action (reducing dopaminergic and serotonergic uptake) is similar to other commonly used antidepressants.
Some studies have taken place in humans. A single dose was shown to alter brain waves in healthy volunteers, who showed increased alpha activity and an associated decrease of slow activity and of fast activity in the frontal cortex. These results imply that nebracetam might improve linguistic learning and memory processing. A trial in dementia patients reported that significant clinical improvement occurred after 8 weeks. However, other studies did not replicate this finding.
Nebracetam Side Effects
Nebracetam seems to be quite safe, but large-scale clinical trials have not taken place. The clinical study in Alzheimer’s patients reported that one subject had minor skin eruptions during the trial. The effective dose in rodents (10 mg/kg) is considerably lower than the LD50 dose (257 mg/kg) that is lethal in 50% of tested subjects.
It is estimated that 20% of the plasma (blood) concentration ultimately crosses the blood-brain barrier to reach the central nervous system. Most studies have been done in animal models and employed dosages of 10 mg/kg/day. This is equivalent to approximately 700 mg/day in an average sized adult (70 kg or 154 lbs.). A study in health adult males was performed to assess the effect of 2 doses (200 and 600 mg) on visual spatial attention, but it did not find any significant improvements with either dose. A clinical trial in human subjects with dementia administered 800 mg/day (2 doses of 400 mg each) and did find improvement on a clinical dementia rating after 8 weeks.
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