From: Anders Sandberg (asa@nada.kth.se)
Date: Sat May 22 1999 - 08:48:30 MDT
"James D. Wilson" <netsurf@sersol.com> writes:
> You are talking about Provigil, and I started taking it as an
> alternative to Ritalin two weeks ago. What do you want to know?
A bit of medline on modafinil (the active substance) below. Overall,
it looks fairly safe, does not affect the hormone system too much,
might worsen hypertension and might make you think that you are more
alert and efficient than you are.
Any bet how quickly use of it for purposes other than narcolepsy will
be classed as narcotics? ;-)
Aviat Space Environ Med 1999 May;70(5):493-8
Naps and modafinil as countermeasures for the effects of sleep
deprivation on cognitive performance.
Batejat DM, Lagarde DP
Institut De Medecine Aerospatiale du Service De Sante Des Armees,
Bretigny sur Orge, France.
Disruptions in wake-sleep rhythms, particularly induced by sleep
deprivation are limiting factors for military personnel in operations.
The role of sleep and naps in the recovery of performance is generally
accepted. Pharmacological aids, for example hypnotic or stimulant
substances can also be effective countermeasures. Recently, a new
stimulant compound, modafinil (MODIODAL) has also proven
effective. Considering the excellent results obtained with napping and
modafinil, we have studied the combined effect of these two
countermeasures on psychomotor performance under conditions simulating
an operational situation. Beneficial effects of a few hours' nap on
performance were confirmed. Consequently naps should be encouraged,
even if limited and diurnal. Modafinil, which combines wakening and
stimulating properties without any known side effects, was useful for
longer periods of sleep deprivation and when there was no real
possibility of sleep recovery. Modafinil did not prevent sleep if
sleep opportunities were available. The combination of naps and
modafinil demonstrated the best cognitive performance during sleep
deprivation.
Clin Pharmacol Ther 1999 Mar;65(3):328-35
Does short-term treatment with modafinil affect blood pressure in
patients with obstructive sleep apnea?
Heitmann J, Cassel W, Grote L, Bickel U, Hartlaub U, Penzel T, Peter JH
Department of Medicine, Marburg University,
Germany. heitmanj@mailer.uni-marburg.de
OBJECTIVE: To investigate the effects of modafinil, a central
nonamphetamine awakening substance, on blood pressure and heart rate
in hypersomnolent patients with obstructive sleep apnea. DESIGN: This
double-blind, randomized, placebo-controlled crossover trial was
performed over 2 days and 3 nights in a single-center study of
hospitalized patients from a referred care center. Twenty-six
otherwise healthy men (age range, 30 to 60 years) with mild to
moderate obstructive sleep apnea were recruited by the outpatient
department of the Marburg University Sleep Laboratory. Patients were
given 200 mg oral modafinil in the morning and 100 mg at
midday. Placebo was given in the same manner in a crossover
design. Mean arterial (radial) blood pressure was monitored
continuously during nocturnal sleep and during a series of
standardized daytime physical and psychologic performance tests.
RESULTS: The difference in the main end point between the treatment
with modafinil and placebo was 1.17+/-0.83 (mean +/- SE) mm Hg (95%
confidence interval: -0.56 to 2.91 mm Hg). The maximal differences in
blood pressure values occurred under loaded conditions (systolic blood
pressure, ergometry: 5.62+/-1.13 mm Hg; mental stress test:
6.19+/-1.33 mm Hg). CONCLUSION: Short-term administration of modafinil
did not elicit a significant response with regard to the main end
point. However, cardiovascular effects during mental and physical load
were observed. Longterm studies that include subjects with
hypertension are necessary to investigate the clinical relevance of
the cardiovascular effects of modafinil.
J Clin Pharmacol 1999 Jan;39(1):30-40
A double-blind, placebo-controlled, ascending-dose evaluation of the
pharmacokinetics and tolerability of modafinil tablets in healthy male
volunteers.
Wong YN, Simcoe D, Hartman LN, Laughton WB, King SP, McCormick GC,
Grebow PE
Drug Safety and Disposition, Cephalon, Inc., West Chester,
Pennsylvania, USA.
A randomized, double-blind, placebo-controlled, ascending-dose study
was conducted to evaluate the pharmacokinetic and safety profiles of
increasing modafinil doses (200 mg, 400 mg, 600 mg, 800 mg)
administered orally over a 7-day period in normal healthy male
volunteers. Eight subjects (six modafinil; two placebo) were
randomized to each of the four dose groups. Modafinil or a placebo was
administered once daily for 7 days. Serial blood samples were obtained
following administration of the day 1 and day 7 doses for
characterization of pharmacokinetics, and trough samples were obtained
prior to dosing on days 2 through 6 to assess the time to reach the
steady state. Pharmacokinetic parameters were calculated using
noncompartmental methods. Modafinil steady state was reached after
three daily doses. Modafinil pharmacokinetics were dose and time
independent over the range of 200 mg to 800 mg. Steady-state
pharmacokinetics of modafinil were characterized by a rapid oral
absorption rate, a low plasma clearance of approximately 50 mL/min, a
volume of distribution of approximately 0.8 L/kg, and a long half-life
of approximately 15 hr. Modafinil was primarily eliminated by
metabolism. Modafinil acid was the major urinary
metabolite. Stereospecific pharmacokinetics of modafinil were
demonstrated. The d-modafinil enantiomer was eliminated at a threefold
faster rate than 1-modafinil. Modafinil 200 mg, 400 mg, and 600 mg
doses were generally well tolerated. The modafinil 800 mg dose panel
was discontinued after 3 days of treatment due to the observation of
increased blood pressure and pulse rate. The safety data from this
study suggest that the maximum tolerable single daily oral modafinil
dose, without titration, may be 600 mg.
J Sleep Res 1998 Jun;7(2):105-14
Effect of modafinil on plasma melatonin, cortisol and growth hormone
rhythms, rectal temperature and performance in healthy subjects during
a 36 h sleep deprivation.
Brun J, Chamba G, Khalfallah Y, Girard P, Boissy I, Bastuji H,
Sassolas G, Claustrat B
Service de Radiopharmacie et Radioanalyse, Centre de Medecine
Nucleaire, Hopital NeuroCardiologique, Lyon, France.
Modafinil is an alerting substance which has been used successfully to
treat narcolepsy. Nothing is known about its effect on hormone
secretions. For this purpose, eight healthy young men were enrolled in
a double blind trial to test the effects of modafinil on daily plasma
melatonin, cortisol and growth hormone (GH) rhythms. Blood was sampled
for hormone assays, every hour during the daytime and every 30 min
during the nighttime. In addition, rectal temperature and mental
performances were determined during the study which comprised 3
sessions, two weeks apart: a 24 h control session including a night
with sleep (S1) and two 48 h sessions S2 and S3 with a sleep-deprived
night (N1) followed by a recovery night (N2). Modafinil (300 mg x 2)
or placebo were randomly attributed during N1 at 22 h and 8 h. As
expected, performance was improved after modafinil administration and
body temperature was maintained or increased. Plasma melatonin and
cortisol profiles were similar after modafinil and placebo
administration. The levels observed during the recovery and the
control nights (N2) displayed no difference. For GH, during both sleep
deprived nights, secretion was dramatically reduced compared with the
control one, although the number of secretory episodes was unchanged.
These data show that the alerting property of modafinil is not related
to an alteration of hormone profiles and suggest that the acute
modafinil administration is devoid of short-term side-effects.
J Sleep Res 1997 Jun;6(2):84-91
Self-monitoring cognitive performance during sleep deprivation: effects of
modafinil, d-amphetamine and placebo.
Baranski JV, Pigeau RA
Information Processing Sector, Defence and Civil Institute of Environmental Medicine, North York, Ontario, Canada.
joe.baranski@dciem.dnd.ca
Self-monitoring refers to the ability to assess accurately one's own
performance in a specific environment. The present study investigated
the effects of the stimulating drugs modafinil (300 mg) and
d-amphetamine (20 mg) on the ability to self-monitor cognitive
performance during 64 h of sleep deprivation (SD) and sustained mental
work. Two cognitive tasks were investigated: a visual (perceptual)
judgement task and a complex mental addition task. Subjects in the
placebo condition displayed marked circadian and SD effects on
cognitive task performance but their self-monitoring was substantively
undisturbed by SD. Subjects performing under the influence of
d-amphetamine likewise displayed highly proficient self-monitoring
throughout the SD period. In contrast, modafinil had a disruptive
effect on self-monitoring, inducing a reliable 'overconfidence' effect
(i.e. an overestimation of actual cognitive performance), which was
particularly marked 2-4 h post-dose. Although modafinil has proven to
be a safe and effective countermeasure to the effects of extensive SD
on cognitive task performance, we encourage a more comprehensive
understanding of the relation between its subjective and performance
enhancing effects before the drug is recommended as a viable fatigue
countermeasure.
-----------------------------------------------------------------------
Anders Sandberg Towards Ascension!
asa@nada.kth.se http://www.nada.kth.se/~asa/
GCS/M/S/O d++ -p+ c++++ !l u+ e++ m++ s+/+ n--- h+/* f+ g+ w++ t+ r+ !y
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