Adrafinil

Product Description

History

The French drug manufacturer, Lafon, discovered adrafinil during the late 1970s. It was initially marjeted in France on 1986 a treatment for excessive sleepiness of narcolepsy. During the subsequent years however, Lafon developed modafinil – a metabolite of adrafinil. From then on, modafinil was favored by users as it is more potent and lesser side effects. Currently, adrafanil remains to be uncontrolled by the US FDA. France who had previously licensed its use withdrew the marketing permission of adrafinil (under the brand name Olmifon) last September 2011. It is currently available as a prescription drug in New Zealand [1].

Chemical structure

Adrafinil has similar molecular structure with modafinil. Interestingly, when adrafinil is metabolized by the body, it becomes modafinil, hence, both exhibit nearly identical effects. Both belong to a new class of drugs known as “eugregoric” or good arousal [Milgram]. Many people consider these supplements as nootropic agents.

[msgbox]Chemical name/IUPAC: Benzhydryl sulphinyl-autohydroxamic acid

Chemical formula: C15H15NO3S [2]

Chemical properties: Light pink solid

Usage: alpha adrenergic agonist

Materials (Raw): Bromodiphenylmethane, 2-N-butoxyethylmethacrylate, hydroxylamine hydrochloride[/msgbox]

Adrafinil is a stimulant, however, it is different compared to other conventional stimulants. Known cognitive stimulants such as amphetamine salts, methylphenidate and methamphetamine energize and even increase alertness. However, these are highly addictive chemicals unlike adrafinil and modafinil. The aforementioned stimulants are gentler, thereby producing similar stimulating effects with less agitation, apprehension, excess locomotor activity, insomnia, nervousness and other effects of prolonged stimulant use.

Mechanism(s) of action

Alpha 1 adrenergic receptor mechanism

Adrafinil and modafinil release their effects through stimulating particular adrenergic neuron receptors in the brain stem and hypothalamus. These parts of the brain regulate alertness and normal wakefulness through norepinephrine – a neurotransmitter associated to memory, learning, and attentiveness. Both adrafinil and modafinil stimulates the receptor sites of norepinephrine known as alpha-1 adrenergic. This leads to maintenance of learning, memory and attention. Additionally, it exerts neuroprotective properties without interfering to other brain activities unlike other stimulants [2].

Modification of GABA and glutamate release mechanism

Another reported mechanism of adrafinil and modafinil includes its ability to decrease or inhibit GABA in the posterior hypothalamus, nucleus accumbens, cortex and preoptic area of hypothalamus. Some studies also discovered that adrafinil and modafinil seems to increase glutamate in the lateral and ventromedial thalamus. This paradoxical mechanism indicates wake and alertness promotion [3].

Brain metabolism mechanism

On this particular hypothesis, adrafinil is thought to be indirectly linked to any neurotransmitter system. Instead, it is proposed to increase cerebral metabolism activity on the hippocampus, thalamus and amygdala. This particular activity leads to increase glutamine synthetase which is being synthesized to glutamine. With enhanced glutamate synthesis, there is improved awareness and wakefulness [2],[3].

Benefits

Comparably, there is less literature intended to discuss the benefits of adrafinil than modafinil. As such, the following studies reflect human trials using modafinil to indicate the beneficial effects of adrafinil.

Narcolepsy treatment

Adrafinil was primarily developed by Lafon pharmaceutical company to induce wakefulness. Thus, it is primarily indicated for narcoleptic individuals. In a particular study, the effects of modafinil on narcolepsy were measured. 151 individuals diagnosed with excessive sleepiness were asked to take for 6 weeks. After which, the efficacy of the drug was evaluated by the researchers through the use of checklists and surveys.

Analysis of data gathered revealed that modafinil can significantly enhance the health related quality of life of the participants including energy, physical and social functioning. Moreover, it can help in decreasing fatigue whilst increasing cognitive functioning [4].

In a double-blind research published on the same year as above study, the effect of modafinil on narcolepsy was further deliberated. Participants received modafinil for three weeks. After data gathering, statistical analysis was done revealing increased in vigilance amongst narcoleptic patients. Modafinil is said to have exerted its mechanisms on the left hemisphere of the brain [5].

Primary insomnia treatment

Individuals diagnosed with primary insomnia experiences frank fatigue and daytime sleepiness. Since, modafinil is known to help in increasing alertness; it was hypothesized that it can help in alleviating the effects of insomnia. 30 participants were enlisted in the study in which they were randomly enrolled to three different treatment including a) placebo plus cognitive behavioral therapy, b) modafinil plus cognitive behavior therapy and c) modafinil only.

Results showed that modafinil plus cognitive behavior therapy is most effective in improving sleep profile than modafinil administration alone. Additionally, it was revealed that modafinil can diminish adverse effects of cognitive behavioral therapy. It can enhance sleep latency, decrease daytime sleepiness and improve compliance to prescribed therapy [6].

Fatigue alleviation

Fatigue is one of the most common symptoms experienced by individuals diagnosed with chronic disorders. The following studies revealed how modafinil can alleviate fatigue on patients with lung cancer, multiple sclerosis and Parkinson’s disease.

Parkinson’s disease

42% of individuals diagnosed with Parkinson’s disease (PD) complain about experiencing fatigue. With this overwhelming population, there are still no recognized treatments for PD related exhaustion. As such, the authors of the study recruited patients with idiopathic PD. Fortunately, 13 individuals participated and were randomly given placebo and modafinil for 4 weeks. Results showed that PD patients taking modafinil experienced greater alleviation of fatigue and sleep improvement compared to the placebo group. This study demonstrates that modafinil can help in alleviating PD related fatigue [7].

Multiple sclerosis

In another study aiming to disclose the effects of modafinil in fatigue, multiple sclerosis (MS) patients were enlisted as participants. A total of 50 MS patients joined the study and were given low doses of modafinil for three months. Comparison of baseline data and subsequent evaluation revealed that 91.5% of the respondents had improved clinical conditions. Data showed that there was a significant improvement on sleepiness and fatigue [8].

Lung cancer

One of the most difficult and predominant symptoms experienced by individuals diagnosed with advanced cancer is fatigue. As such, healthcare providers always prescribe central nervous stimulants to relieve cancer-related fatigue. These traditional CNS stimulants however have various adverse effects, and since modafinil is known to act on certain areas of the brain, the researchers attempted to study if this particular alpha adrenergic receptor is better tolerated by cancer patients. 15 individuals diagnosed with “non-small cell lung cancer” were enlisted on a randomized trial. Participants were given doses of modafinil for 2 weeks. After the study period, data were analyzed revealing that modafinil can help overcome fatigue whilst decrease daytime sleepiness and depression symptoms [9].

Attention and behavior enhancement

In an early academic review, adrafinil was thought to have “behavioral-activating effects.” French studies had also shown that it can promote vigilance and enhance moods on the elderly [2]. Similarly, even modafinil, an enantiomer of adrafinil is hypothesized to share the same mechanism. As such, a study was undertaken to assess whether modafinil can improve attention and behavior. Cancer patients were enlisted as participants and they were randomly given doses of modafinil and placebo. After the study period, it was revealed that modafinil can improve depression, sleepiness, attention and psychomotor speed [10].

These human studies only show that modafinil and adrafinil has many potential benefits to everyone without causing any serious side/adverse effects. However, it is critical that users take precautions when taking un-prescribed drugs.

Additional Information

Grams

10, 20, 30, 40