12.6: Cognitive Enhancers: Cholinesterase Inhibitors and NMDA Receptor Antagonists

Cognitive enhancers, also known as "smart drugs," are substances used to enhance memory, mental alertness, and concentration. These can be natural or synthetic and improve cognition in conditions like Alzheimer's disease (AD) and other neurodegenerative diseases. Some common examples include caffeine, amphetamines, methylphenidate, modafinil, arecoline, donepezil, vortioxetine, and piracetam. These enhancers work on the principle of synaptic plasticity and altered circuit function. They stimulate the brain's neurotransmitters, enhancing neuron communications and improving cognition and memory. This is particularly beneficial for treating neurodegenerative diseases where cognitive functions are compromised. However, the increasing popularity of these cognitive enhancers has led to misuse and abuse. While they are intended for medical treatments, some misuse them to boost cognitive performance, leading to potential health risks. Overuse can lead to tolerance, where higher doses are required to achieve the same effects, and in severe cases, addiction.

CANTAB tests, a series of computer-based cognitive assessments, are often used to evaluate the effectiveness of these cognitive enhancers. They measure various aspects of cognition, including attention, episodic memory, working memory, decision-making, and response control. While cognitive enhancers have shown promise in improving these aspects, their misuse can have the opposite effect, causing cognitive impairment and other health issues. In conclusion, while cognitive enhancers hold the potential to treat neurodegenerative diseases and improve cognition, their misuse can lead to significant health risks. These substances must be used responsibly and under the supervision of a healthcare professional to minimize the risk of abuse and addiction.

'Cognition' encompasses various aspects of mental function, assessed using tests like the Cambridge Neuropsychological Test Automated Battery.

Cognitive enhancers, or nootropic drugs,  boost mental function and are used as performance enhancers.

Acetylcholinesterase inhibitors improve memory and cognition in mild to moderate cases of Alzheimer's disease. However, they can induce unwanted cholinergic effects such as salivation, lacrimation, drowsiness, urinary retention, and bowel disorders.

NMDA antagonists alter synaptic plasticity and the brain's circuit function.

Synaptic plasticity involves long-term potentiation and depression, induced by glutamate receptor activation and modulated by dopamine.

Memantine inhibits NMDA receptor-mediated excitotoxicity. It also limits neuronal Ca²⁺ influx, preventing intracellular toxic levels. It is used in moderate to severe cases of Alzheimer's disease.

Other drugs include modafinil, which increases extracellular dopamine levels and glutamate release while inhibiting the release of GABA. It is used in ADHD treatment.

Piracetam, a positive allosteric AMPA receptor modulator, helps improve memory and cognition.