Didesoxymodafinil

Didesoxymodafinil is a direct analogue of modafinil. While the chemical structure of the latter is 2-[(diphenylmethyl)sulfinyl]acetamide, the former didesoxymodafinil differs in two key ways: it lacks the sulfoxide oxygen atom (it has a sulfur-carbon bond instead of a sulfur-oxygen double bond), and it lacks the terminal acetamide group, replaced by a simple ethylamine chain.

Those changes made it a simpler, potentially more lipophilic (fat-soluble) molecule, to which it owes its superior bioavailability relative to that of modafinil, which it surpasses by impressive 20%. Its, increased lipophilicity leads to faster brain penetration. While this particular property could be expected to shorten its action, animal studies suggest otherwise. In a dog study, it shortened wakefulness latency by 68% time than modafinil and laster longer.

Compared to its “founding compound”, didesoxymodafinil’s selectivity as dopamine reuptake inhibitor (DAT) is greater – as evidenced in studies in cell models, approximately two-fold. Rat studies show that while its administration resulted in a 150% increase in extracellular dopamine concentration in the striatum, effects on other monoamine neurotransmitters were negligible.

Unlike modafinil, didesoxymodafinil exhibits weaker affinity for OX1R and OX2R orexin receptors. Interestingly enough, in studies using transgenic orexin-deficient mice, it maintained approximately 60% efficacy in promoting wakefulness, which suggests an orexin-independent mechanism of action.
Didesoxymodafinil has also been found to possess some effects on adenosine receptors, being a weak antagonist of A1 and A2A receptors, which may contribute to its stimulant effects, albeit to a limited extent relative to modafinil or caffeine. Without the amide, it may have a less pronounced histaminergic effect (which contributes to modafinil’s wakefulness), placing more emphasis on the dopaminergic component.

Moreover, animal studies led to the discovery of other interesting properties of the compound in question. It has been found to improve spatial memory in rats after mere 3 days of administration, allowing the animals to reach the target 40% faster than controls. As it turns out, didesoxymodafinil happens to possess considerable neuroprotective properties, as it has been to proven protect against brain ischemia in rat models, reducing its scope by 35%. The mechanism of action behind this finding might be linked to the activation of the PI3K/Akt pathway and enhanced expression of anti-apoptotic proteins.

As for its subjective effects, their profile seems to resemble those of modafinil and flmodafinil, placing didesoxymodafinil somewhere in the middle ground between those two. Compared to modafinil, it feels less energizing and its effects on mood are rather subtle. On the other hand, its wakefulness and focus might be described as sharper and more hyperfocus-like vs. the effects produced by flmdafinil. As such, it is not very likely to encourage physical activity, but could be a useful study aid as a “non-distracting” stimulant.

It has to be emphasized that didesoxymodafinil was never studied in humans. As such, risks associated with its use remain potentially unknown. It is strongly advised to approach this substance with caution.

Benefits of taking didesoxymodafinil

• reduced fatigue in times of sleep deprivation;
• increased alertness and wakefulness;
• enhanced concentration and focus;
• greater ability to sustain attention for prolonged periods of time;
• improved working and spacial memory;
• increased processing speed;
• slight boost in energy;
• mild lift in mood;
• decreased impulsivity;
• enhanced emotion regulation;
• neuroprotective effects.

Side effects

• headache;
• reduced appetite;
• anxiety;
• insomnia;
• irritability;
• peripheral vasoconstriction;
• elevated liver enzymes (long-term, high-dose use).

Interactions

• CYP2C19 substrates (SSRI) – dose adjustment might be necessary;
• other CNS stimulants – risk of overstimulation and adverse cardiac events.

Dosage

In the absence of human data, dosing strategy for didesoxymodafinil might be extrapolated from its comparison with modafinil.

Based on the assumption that it could potentially be both faster- and longer-acting than its parent compound, and one with superior strength, it is recommended to start as low as 25 mg to assess one’s individual tolerance, then gradually increase the dose as needed.

In case of no significant adverse effects, doses of 100 mg and above should generally be safe, however, it is reasonable to set the limit at around 150 mg.