Posted by temoigneur on June 11, 2007, at 22:20:18
In reply to Re: Modafinil (Provigil, Alertec) a short term mir, posted by Sigismund on June 11, 2007, at 3:24:25
The Good Drug Guide
"...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-induced alertness is partially antagonised by the endogenous cannabinoid neurotransmitter anandamide. 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; methamphetamine ('Ice') abuse; apathy in the elderly; jet-lag; cancer-associated fatigue and opioid-induced sedation; fatigue in Charcot-Marie-Tooth Disease (CMT); and everyday cat-napping. Sceptics cite the broadly comparable therapeutic equivalance of a cup of coffee.
There is tentative evidence that modafinil may be neuroprotective against the "dopamine-deficiency disorder" Parkinson's disease. 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. Modafinil was reportedly used by Allied combat soldiers in both Gulf Wars, though this seems unlikely to feature prominently in its future promotional literature.
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 August 2006 Cephalon unexpectedly received a 'non-approvable' letter from the FDA for modafinil tablets branded as Sparlon. Taken in this guise, modafinil was intended for the treatment of so-called attention-deficit/hyperactivity disorder (ADHD) in children and adolescents. The FDA's rejection of modafinil/Sparlon for ADHD was based on a single adverse incident during clinical trials. One child developed a rash suggestive of Stevens-Johnson syndrome - a serious hypersensitivity complex affecting the skin and mucous membranes. There is no evidence that Stevens-Johnson syndrome is more common in adult modafinil users. The physician who diagnosed SJS in the affected 10 year old later recanted the diagnosis. Meanwhile, millions of lively American school students controversially diagnosed with ADHD continue to be prescribed toxic amphetamine-based products instead.
Modafinil is used experimentally in the treatment of "atypical" depression. Atypical depression is marked by hypersomnia, hyperphagia [over-eating], low energy, and rejection-sensitivity. The syndrome is actually quite common. The results of preliminary studies have been encouraging, but large-scale trials are needed.
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..."
poster:temoigneur
thread:762296
URL: http://www.dr-bob.org/babble/20070604/msgs/762513.html