Modafinil? interesting..
"...modafinil ('Provigil', 'Alertec', 'Vigicer', 'Modalert', etc) is a memory-improving and mood-brightening psychostimulant. It enhances wakefulness and vigilance, but its pharmacological profile is notably different from the amphetamines, methylphenidate (Ritalin) or cocaine. Modafinil is less likely to cause jitteriness, anxiety, or excess locomotor activity - or lead to a hypersomnolent 'rebound effect' - than traditional stimulants. Subjectively, it feels smoother and cleaner than the amphetamines too. It may even be anxiolytic. The normal elimination half-life of modafinil in humans is between 12 - 15 hours. So it's worth fine-tuning one's dosage schedule accordingly.
Current research suggests modafinil, like its older and better-tested analogue adrafinil, is a safe, effective and well-tolerated agent. It is long-acting and doesn't tend to cause peripheral sympathetic stimulation. Yet its CNS action isn't fully understood. Modafinil induces wakefulness in part by its action in the anterior hypothalamus. Its dopamine-releasing action in the nucleus accumbens is weak and dose-dependent; the likelihood of a euphoric response ('abuse potential'), dose-escalation and tolerance is thus apparently small. Modafinil has central alpha 1-adrenergic agonist effects i.e. it directly stimulates the receptors. Modafinil inhibits the reuptake of noradrenaline by the noradrenergic terminals on sleep-promoting neurons of ventrolateral preoptic nucleus (VLPO). More significant, perhaps, is its ability to increase excitatory glutamatergic transmission. This reduces local GABAergic transmission, thereby diminishing GABA(A) receptor signalling on the mesolimbic dopamine terminals.
Modafinil is proving clinically useful in the treatment of narcolepsy, a neurological disorder marked by uncontrollable attacks of daytime sleepiness. Narcolepsy is caused by dysfunction of a family of wakefulness-promoting and sleep-suppressing peptides, the orexins. Orexin neurons are activated by modafinil. Orexinergic neurons are found exclusively in the lateral hypothalamic area. Their activation is associated with enhanced pleasure-seeking and motivation as well as arousal. Orexinergic fibers project to the entire central nervous system. Genetically modified orexin-knockout animals offer a model of human narcolepsy. Narcoleptics suffer profound disturbances in normal sleeping patterns and variable degrees of depression. These symptoms can be reversed with modafinil. Selective orexin receptor agonists of the future may prove useful both to narcoleptics and the population at large.
Experimentally, modafinil is also used in the treatment of Alzheimer's disease, depression, attention-deficit disorder (ADHD), myotonic dystrophy, multiple sclerosis-induced fatigue, post-anaesthesia grogginess, cognitive impairment in schizophrenia, spasticity associated with cerebral palsy, age-related memory decline, idiopathic hypersomnia, jet-lag, and everyday cat-napping. Depressives who feel sleepy and fatigued on SSRIs can augment their regimen with modafinil. In September 2003, an advisory panel to the FDA endorsed its use for treating shift work sleep disorder and obstructive sleep apnea.
The US military are interested in modafinil too.
Modafanil is marketed as 'Alertec" in Canada - and over the Net. 'Alertec' is less expensive than 'Provigil'. Cheap generic modafinil has been available since 2006. But Cephalon is vigorously litigating to defend its patents.
In March 2005, Cephalon filed a New Drug Application (NDA) with the FDA for 'Nuvigil' (r-modafinil, armodafinil) - a single isomer formulation of modafinil. Nuvigil will be marketed aggressively to offset the anticipated loss of revenue from Provigil.
Modafinil is increasingly used as a 'lifestyle drug' - a lucrative 'off-label' market its makers have not been unduly keen to discourage. Some prescribing physicians have reportedly been surprised at a previously hidden epidemic of narcolepsy among hard-working young professionals attending their surgeries.
Prudence, however, should be exercised in drastically curtailing one's sleep. Prolonged sleeplessness weakens immune function. Animals tortured in sleep-deprivation experiments eventually die from massive bacterial infections of the blood..."
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