IDRA-21: Review of Nootropic Benefits, Uses, Dosage, & Side Effects

Updated on January 26, 2024
 by — reviewed by Jason Williams, PhD (Contributor: George Collins / Editor: Yoko Hill)
Insights into IDRA-21's nootropic benefits and impact on neural connections.

If you’ve been looking for an edge to boost your cognitive performance, you may have come across IDRA-21.

IDRA-21 is a nootropic compound that is claimed to offer various benefits, including improved cognitive function and increased intelligence. 

But, how does IDRA-21 work?

What does the clinical data provided say about this nootropic drug?

In this article, we will discuss the evidence for these claims, safe dosage, and the potential risks and side effects associated with IDRA-21 use.

What is IDRA-21?

IDRA-21 (chemical structure is C8H9ClN2O2S) is an ampakine drug and is classified as a benzothiadiazine derivative, which acts as a positive allosteric modulator of AMPA receptors in the brain. These receptors play a critical role in stimulating synapses for increased transmission and plasticity, which are foundational for cognitive processes. 

The IDRA-21 nootropic is noted for its current potential to promote cognitive enhancement and improve memory, including visual recognition memory, without the desensitization often associated with other AMPA receptor modulators.(1)

This compound is particularly interesting in neuropharmacological research due to its ability to facilitate excitatory neurotransmission, which could theoretically attenuate cognitive impairments associated with conditions like Alzheimer’s disease.

IDRA-21 has been studied in monkeys, where it worked at improving cognitive performance on tasks requiring focus. (2)

Its potency as a cognitive enhancer is attributed to its mechanism of action, as it works as a partial modulator of glutamate AMPA receptors and boosts glutamate neurotransmission through this modulation.

Research indicates that IDRA-21, derived from the benzothiadiazine chemical, is 30 times more potent than aniracetam, another nootropic and one of the most popular cognition enhancers in the same class. It crosses the blood-brain barrier and works to reverse cognitive deficits induced by certain agents like alprazolam or scopolamine more effectively.(3)

Currently, IDRA-21 is available for laboratory research use and is not approved by the FDA (Food and Drug Administration) for intended therapeutic use in humans.

Pros:

  • Demonstrates a dramatic improvement in cognitive functions, possibly reversing damage in elderly subjects
  • Benefits may last for up to three days from just a single dose​
  • Boosts neurotransmission and mental clarity

Cons:

  • Difficult to find high-quality IDRA-21
  • Most of the benefits have been observed in animal (rat and monkey) studies, with a lack of human studies to determine its long-term pharmacological efficacy

Mechanism of Action

IDRA-21 (scientific name known as 7-chloro-3-methyl-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide) is one of the ampakines, a class of compounds known for their role in enhancing cognitive function, and it contains a benzothiadiazine chemical structure.

IDRA-21 works by stimulating positive allosteric modulation of the glutamate AMPA receptors. This modulation is critical for the drug’s cognitive-enhancing effects, as taking IDRA-21 facilitates the synaptic transmission and plasticity related to learning and memory.(4)

The molecular research purposes for IDRA-21 also include examining its congener relationship with aniracetam, another well-known nootropic. Unlike aniracetam, however, IDRA-21 doesn’t just potentiate AMPA receptor function but also seems to prevent the desensitization of these receptors, which could be beneficial for maintaining cognitive function over longer periods.

This mechanism is also what contributes towards the neuroprotection provided by IDRA-21 against neurodegenerative diseases, such as preventing the cause of dementia.(5)

This molecular activation positions IDRA-21 as a significant compound for research purposes, with a particular interest in its potential to abate pharmacologically induced cognitive impairments.

Nootropic Benefits of IDRA-21

IDRA-21 is one of the most diverse nootropics that offers several cognitive benefits. The technical data provided in various studies, including those involving the water maze tests typically used to measure cognitive function in research animals, support these benefits.

Here is a brief list of the most notable nootropic benefits of IDRA-21.

 1. Improved Learning and Memory

IDRA-21 can significantly enhance learning and memory capabilities, which may also translate to visual recognition improvements. This is due to the positive modulation of AMPA receptors and the stimulation of the glutamate neurotransmitter.(6)

2. Enhanced Focus and Attention

IDRA-21 is known to enhance focus and attention, likely due to its positive allosteric modulation of AMPA receptors. This action increases excitatory synaptic transmission, which is crucial for maintaining alertness and the ability to concentrate on tasks.

3. Mood and Energy Level Improvement

There are indications that IDRA-21 may have a positive impact on mood and energy levels, which can be beneficial in depressive states. This effect may also relate to its potential to address cognitive deficits associated with the cause of dementia.

4. Increased Excitatory Synaptic Strength

IDRA-21 enhances excitatory synaptic strength, which is crucial for efficient neurotransmission and cellular hippocampal health, both of which are vital for cognitive functions and brain health.

IDRA-21 acts as an inhibitor in a unique way, distinct from its known positive modulation of AMPA receptors. In a study, IDRA-21 showed inhibitory effects on synaptic and extrasynaptic NMDA (N-methyl-D-aspartate) receptor-mediated events in cultured cerebellar granule cells.(5)

The compound reduces NMDA receptor whole-cell currents and also shortens the duration of miniature excitatory postsynaptic currents mediated by NMDARs without affecting their peak amplitude. 

The study further revealed that IDRA-21 has partial selectivity for NMDA receptor subunits, being more effective on NR1a-NR2B than NR1a-NR2A receptors to boost neurotransmitters. This suggests that IDRA-21 has a subunit-selective negative modulation effect on NMDA receptors, which could contribute to its nootropic benefits.

Uses of IDRA-2

IDRA-21 is used for the following purposes:

  • Enhances learning and memory, especially in elderly subjects with age-related cognitive decline.
  • Reduces cognitive impairment induced by substances like scopolamine or alprazolam.
  • Improves performance on tasks measuring visual recognition memory.
  • Used off-label as a nootropic supplement to improve cognitive function, memory, and learning.

IDRA-21 is seen as a promising solution for cognitive enhancement and receives attention for its material benefits.

Where To Buy IDRA-21

Your search for IDRA-21 stops here!

We recommend buying IDRA-21 from Science.bio. They are a reputable nootropic vendor that offers high-quality products at competitive prices.

Science.bio offers 1st and 3rd party lab-tested products with a Certificate of Analysis (CoA). This ensures that their products are high quality and free of impurities. They include natural products and chemical products and will ship your order anywhere in the world, with free delivery for orders over $100. 

IDRA-21 comes in powder form in different sizes – 500 mg, 1000 mg, and 5000 mg. Studies done on animals have used the dose range of 0.15-10 mg/kg. Oral administration of IDRA-21 significantly improved performance on a computer-automated delayed matching-to-sample task.

The daily recommended IDRA-21 dosage for humans is roughly 10 mg to 20 mg.

IDRA-21 Side Effects and Safety

Common side effects of IDRA-21 include:

  • Headache
  • Dizziness
  • Nausea
  • Fatigue
  • Anxiety
  • Irritability

Each side effect listed is typically mild and doesn’t last long. However, if a side effect lasts, then lower your IDRA-21 dose or try using it with choline supplements in a nootropic stack.

Note: Although IDRA-21 doesn’t seem to increase neurotoxicity under normal conditions, a study from 2004 published in Annals of Neurology showed that neuronal damage following global ischemia after stroke or seizures could get worse from IDRA-21 use.(7)

Summary

So what do we know about IDRA-21?

IDRA-21 is a potent nootropic in the world of smart drugs that’s known for its cognitive-enhancing effects. It’s often used to improve memory, focus, and learning. IDRA-21 is considered to be safe if used as directed, although it has not been FDA-approved for therapeutic use by humans. 

If you’re looking for a nootropic to improve your cognitive function and prevent cognitive decline, taking IDRA-21 is a great choice! Additionally, it’s available for laboratory research use for those seeking to investigate its effects as one of the most effective cognition enhancers.

Remember to speak to your healthcare provider before you make the decision to add IDRA-21 to your wellness routine. A doctor can help you understand the correct terms of IDRA-21 use for your particular situation, giving you the information you need to avoid misuse.

How long does IDRA-21 take to work?

IDRA-21 typically begins working within an hour of ingestion. However, it may take a few days of consistent use to notice significant cognitive improvements. 

What is the elimination half-life of IDRA-21?

The elimination half-life of IDRA-21 is approximately 12-14 hours. This means that the substance takes about 12-14 hours to decrease to half its initial concentration in the body. Some users report the overall effects of IDRA-21 lasting up to 48 hours.

Should you cycle IDRA-21?

Yes, it is recommended to cycle IDRA-21 to prevent tolerance build-up. A common cycle might involve taking it for four weeks followed by two weeks off.

Can I stack IDRA-21 with other compounds?

Yes, IDRA-21 can be safely stacked with other nootropics. However, due to its potency, it’s advisable to consult a healthcare provider before combining it with other substances.

How should I store IDRA-21?

IDRA-21 should be stored in a cool, dry place away from direct sunlight. It’s also best to keep it in an airtight container to continue to receive its full potency over time.


Sources, Studies, and Scientific Research
  1. Malkova, Ludise et al. “The effects of huperzine A and IDRA 21 on visual recognition memory in young macaques.” Neuropharmacology vol. 60,7-8 (2011): 1262-8. doi:10.1016/j.neuropharm.2010.12.018 
  2. Buccafusco, Jerry J et al. “The effects of IDRA 21, a positive modulator of the AMPA receptor, on delayed matching performance by young and aged rhesus monkeys.” Neuropharmacology vol. 46,1 (2004): 10-22. doi:10.1016/j.neuropharm.2003.07.002 
  3. Thompson, D M et al. “7-Chloro-3-methyl-3,4-dihydro-2H-1,2,4-benzothiadiazine S,S-dioxide (IDRA 21), a congener of aniracetam, potently abates pharmacologically induced cognitive impairments in patas monkeys.” Proceedings of the National Academy of Sciences of the United States of America vol. 92,17 (1995): 7667-71. doi:10.1073/pnas.92.17.7667 
  4. Vandesquille, M et al. “Effects of positive modulators of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors in a benzodiazepine-induced deficit of spatial discrimination in mice.” Journal of psychopharmacology (Oxford, England) vol. 26,6 (2012): 845-56. doi:10.1177/0269881111416692 
  5. Losi, Gabriele et al. “IDRA-21, a positive AMPA receptor modulator, inhibits synaptic and extrasynaptic NMDA receptor mediated events in cultured cerebellar granule cells.” Neuropharmacology vol. 46,8 (2004): 1105-13. doi:10.1016/j.neuropharm.2004.02.011  
  6. McEntee, W J, and T H Crook. “Glutamate: its role in learning, memory, and the aging brain.” Psychopharmacology vol. 111,4 (1993): 391-401. doi:10.1007/BF02253527 
  7. Yamada, K A et al. “The diazoxide derivative IDRA 21 enhances ischemic hippocampal neuron injury.” Annals of neurology vol. 43,5 (1998): 664-9. doi:10.1002/ana.410430517 
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