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Modafinil = neuroprotective?


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#1 doug123

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Posted 11 July 2006 - 12:39 AM


Neurosci Lett. 1999 Nov 19;275(3):215-8.

A stereological study on the neuroprotective actions of acute modafinil treatment on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced nigral lesions of the male black mouse.

Aguirre JA, Cintra A, Hillion J, Narvaez JA, Jansson A, Antonelli T, Ferraro L, Rambert FA, Fuxe K.

Department of Physiology, School of Medicine, Malaga, Spain.

The effect of an acute administration of the vigilance-promoting drug modafinil ((+/-)(diphenyl-methyl)-sulfinyl-2 acetamide; Modiodal) on the nigrostriatal dopamine system was studied after damage induced by MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) by means of immunohistochemistry for tyrosine hydroxylase (TH) and a stereological method. MPTP (40 mg/kg) reduced from 24,380 +/- 902 to 13,501 +/- 522 and from 37,868 +/- 3300 to 20,568 +/- 1270, respectively, the number of TH immunoreactive (IR) and non-TH IR nigral neurons. Co-administration of Modafinil restored to normal the number of these neuronal populations. MPTP treatment induced also a reduction in the volume of TH IR neurons, which was counteracted by Modafinil administration. The data provide morphological evidence, based on unbiased stereological analysis, for a potential neuroprotective role of Modafinil, not only in dopaminergic neurons, but also with a similar magnitude in the non-DA nerve cell population of the substantia nigra after MPTP lesion.These results suggest that Modafinil has a neuroprotective role in the substantia nigra via a still undefined mechanism in which a crucial role of DA uptake blockade should be excluded. Modafinil may therefore have a therapeutic potential in neurodegenerative processes such as those occurring in Parkinson's disease.

PMID: 10580713 [PubMed - indexed for MEDLINE]


Expert Opin Pharmacother. 2006 May;7(7):837-48.

Neuroprotective agents in schizophrenia and affective disorders.

Krebs M, Leopold K, Hinzpeter A, Schaefer M.

Department of Psychiatry and Psychotherapy, Charite-Universitatsmedizin Berlin, Campus Charite Mitte, Schumannstr. 20/21, D-10117 Berlin, Germany. Michael.Krebs@charite.de

With the exception of dementia, the use of neuroprotective agents in psychiatric disorders is not yet well established. However, recent data from brain imaging studies and clinical trials support the view that neurodegenerative mechanisms may play a role in the pathophysiology of schizophrenia and affective disorders. Further evidence for the use of neuroprotective agents can be drawn from the findings that second-generation antipsychotics, mood stabilizers and antidepressants have been shown to have neuroprotective effects in vitro and in vivo. Neuroprotective agents as add-on therapies (e.g., modafinil, erythropoietin, glycine, D-serine, memantine and celecoxib) are currently being evaluated in schizophrenia and related disorders. This paper reviews the current options for neuroprotective treatment approaches focusing on schizophrenia and affective disorders.

PMID: 16634707 [PubMed - in process]


Acta Pharmacol Sin. 2004 Mar;25(3):301-5.


Neuroprotective mechanism of modafinil on Parkinson disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.

Xiao YL, Fu JM, Dong Z, Yang JQ, Zeng FX, Zhu LX, He BC.

Department of Pharmacology, Chongqing Medical University, Chongqing 400016, China. fjmin@21cn.com

AIM: To observe the neuroprotective mechanism of modafinil on Parkinson disease (PD) models induced by 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP). METHODS: The model of PD was induced by intraperitoneally injecting MPTP into C57BL/6J mice for 4 d. Modafinil (i.p., 50 or 100 mg/kg(-1)/d(-1)) was administered at 30 min following MPTP for 4 d and for another 10 d continuously. The contents of dopamine (DA), noradrenaline (NA), 5-hydroxytryptamine (5-HT), gamma-aminobutyric acid (GABA), glutamine (Glu) in the striatum, and the contents of GABA, Glu, malondialdehyde (MDA), and glutathione (GSH) in the substantia nigra (SN) of model mice were determined. RESULTS: Modafinil (50 and 100 mg/kg) prevented against the decrease of the contents of DA, 5-HT, and NA in the striatum and GSH, GABA in the SN induced by MPTP, but reduced the increase of MDA in the SN and GABA in the striatum induced by MPTP. Modafinil preferentially inhibited striatal GABA release, but it did not change the increase of nigrostriatal Glu release induced by MPTP. CONCLUSION: The anti-oxidation and the modulation of nigrostriatal GABA and striatal NA and 5-HT release contributed to the neuroprotective effects of modafinil on PD induced by MPTP.

PMID: 15000882 [PubMed - indexed for MEDLINE]



#2 superiorn

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Posted 11 July 2006 - 02:30 AM

This should be moved to the research thread. And maybe you should do more than alittle pubmed cut and paste.

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#3 zoolander

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Posted 11 July 2006 - 09:08 AM

I disagree on both of your points superiorn. If anything is to be critisized it is your childish antagonist reply. Such behaviour will not be tolerated

I've been watching you and I will be watching you

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#4 Shepard

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Posted 11 July 2006 - 11:34 AM

Okay, I'm not sure if I'm seeing what that picture is supposed to suggest. After examination, I suppose that she is pointing to her eyes. That was not my first thought, though.

After checking out the site, nevermind. Pretty awesome stuff, although one of those pieces of art will now haunt my dreams.

#5 xanadu

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Posted 11 July 2006 - 06:06 PM

Actually, it's true that people should do more than just cut and paste. You can find some data to support any position. I saw posts claiming cocaine was almost harmless. It's in the analysis and reasoning that we get closer to the truth.

#6 Ghostrider

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Posted 17 July 2006 - 07:37 AM

Dude, that hotboxdesign site is creepy. Check out www.digitalblasphemy.com for some more uplifting desktop wallpapers.

#7 Centurion

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Posted 17 July 2006 - 09:10 AM

Okay, I'm not sure if I'm seeing what that picture is supposed to suggest. After examination, I suppose that she is pointing to her eyes. That was not my first thought, though.

After checking out the site, nevermind. Pretty awesome stuff, although one of those pieces of art will now haunt my dreams.


I get you shep, either that or im imposing the darker side of Mulders mind onto my personal image of you.
Lack of tongue would seem to suggest she is pointing to her eyes

#8 doug123

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Posted 31 August 2006 - 10:11 PM

Behav Pharmacol. 2006 Sep;17(5-6):453-62.
Neuroprotective effects of modafinil in a marmoset Parkinson model: behavioral and neurochemical aspects.

van Vliet SA, Vanwersch RA, Jongsma MJ, van der Gugten J, Olivier B, Philippens IH.
aDepartment of Diagnosis and Therapy, TNO Defence, Security and Safety, Rijswijk bDepartment of Psychopharmacology, Utrecht Institute of Pharmaceutical Sciences and Rudolf Magnus Institute of Neurosciences, Utrecht University, Utrecht, The Netherlands.

The vigilance-enhancing agent modafinil has neuroprotective properties: it prevents striatal ischemic injury, nigrostriatal pathway deterioration after partial transsection and intoxication with 1-methyl-1,2,3,6-tetrahydropyridine. The present study determines the protective effects of modafinil in the marmoset 1-methyl-1,2,3,6-tetrahydropyridine Parkinson model on behavior and on monoamine levels. Twelve marmoset monkeys were treated with a total dose of 6 mg/kg 1-methyl-1,2,3,6-tetrahydropyridine. Simultaneously, six animals received a daily oral dose of modafinil (100 mg/kg) and six animals received vehicle for 27 days. Behavior was observed daily and the locomotor activity, hand-eye coordination, small fast movements, anxiety-related behavior and startle response of the animals were tested twice a week for 3 weeks. Modafinil largely prevented the 1-methyl-1,2,3,6-tetrahydropyridine-induced change in observed behavior, locomotor activity, hand-eye coordination and small fast movements, whereas the vehicle could not prevent the devastating effects of 1-methyl-1,2,3,6-tetrahydropyridine. Dopamine levels in the striatum of the vehicle+1-methyl-1,2,3,6-tetrahydropyridine-treated animals were reduced to 5% of control levels, whereas the dopamine levels of the modafinil+1-methyl-1,2,3,6-tetrahydropyridine-treated animals were reduced to 41% of control levels. The present data suggest that modafinil prevents decrease of movement-related behavior and dopamine levels after 1-methyl-1,2,3,6-tetrahydropyridine intoxication and can be an efficaceous pharmacological intervention in the treatment of Parkinson's disease.

PMID: 16940766 [PubMed - in process]



#9 pedr0vsky

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Posted 04 June 2010 - 11:04 AM

"There is tentative evidence that modafinil may be neuroprotective against the "dopamine-deficiency disorder" Parkinson's disease. "

http://www.modafinil.com/

#10 noos

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Posted 08 January 2012 - 11:30 PM

More cut & paste:

Any mechanism involving improved mitochondrial function or free-radical scavenging could, therefore, explain how modafinil enhances neurocognitive function and bolsters serotonin release without stimulating serotonin release on its own (Ferraro et al 2000, 2001, 2005). While no antioxidant or mitochondrial effects of modafinil have been reported in the context of its ability to promote wakefulness or enhance neurotransmitter release, it has been shown that modafinil does have an antioxidant effect that appears to mediate its neuroprotective actions in MPTP-induced neurodegeneration (Xiao et al 2004). The site of action mediating this effect has not yet been elucidated, and there are a number of plausible intracellular targets which we explore here that would explain both modafinil’s stimulant effects, neuroprotective effects, and perhaps its effects as a therapeutic tool in addiction.

In summary, the bulk of research into modafinil’s wake-promoting mechanism has focused mostly on possible extracellular activities of modafinil. We propose that more work be done on examining potential intracellular mechanisms of modafinil and finding a point of convergence of modafinil’s stimulant and neuroprotective effects. It is likely that modafinil both enhances cellular metabolism and reduces free-radicals in neurons (Pierard et al 1995; Xiao et al 2004). Reduction in brain oxidation or an increase in cortical creatine could promote vigilance (Ikeda et al 2005; McMorris et al 2006), and each effect can increase neurotransmitter release by reducing inhibitory KATP-channel activity. Thus, through any disruption in the positive feedback loop of increased free-radical production and reduced ATP production modafinil could potentially exert its neuroprotective and wake-promoting effects.

http://www.ncbi.nlm....les/PMC2654794/

#11 Sovr'gnChancellor£

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Posted 08 January 2012 - 11:52 PM

But....

We need sleep.

#12 noos

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Posted 09 January 2012 - 01:07 AM

But....

We need sleep.


:|?
Have you read the articles? They are not about not sleeping.

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#13 Raptor87

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Posted 09 January 2012 - 01:10 AM

Okay, I'm not sure if I'm seeing what that picture is supposed to suggest. After examination, I suppose that she is pointing to her eyes. That was not my first thought, though.

After checking out the site, nevermind. Pretty awesome stuff, although one of those pieces of art will now haunt my dreams.


I get you shep, either that or im imposing the darker side of Mulders mind onto my personal image of you.
Lack of tongue would seem to suggest she is pointing to her eyes


What the hell are you guys talking about!?

Back to the topic.

What happens to the brains neuroprotective ability when you go off of Modafinil? Hasn't anyone here felt like shit after getting off the drug besides me? I can vouch for that the crash is horrible, not to mention the heightened sense of reflexes that bugs you week and months after going off the drug! These studies would be interesting if you could be on the damn drug constantly, but you cant! Two or even one day is enough for me.




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