QUOTE (jdog)
Perhaps my question is irrelevant since the documentation info you provided states that there hasn't been any evidence of an increase in benifit past a dosage of 200mg. I guess I was just wondering about dosages in the higher range.
Yeah, well -- that prescribing information was published back in 2004.
Here is some new evidence that might suggest it's neuroprotective:
QUOTE
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]
QUOTE
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]
QUOTE
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]
QUOTE
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]
I am a modafinil user and would be interested to as to long term affects but I think at the moment it is very hard to tell.
I take a daily dose of 200 mg, everyone is different. The dose at which it works on you is the best dose to take and you will notice it, its not to say that if you need twice as much you are potentially putting yourself at twice a high risk of toxicity, it’s probably due to your body being more efficient at getting rid of it. As for whether this drug is neuroprotective there is no real way of telling from any of the published articles. The ones quoted above are based on a compound called MPTP, well known in heroin addicts of California in 1982 who got sold a duff batch which later showed to contain this nasty chemical which totally destroyed dopamine cells in their striatal cells causing irreversible Parkinson’s like symptoms on all these poor young fellars. Advice firstly, don’t buy dodgy drugs! From the reports above it seems highly likely that modafinil effects the dopaminergic system. I say this because MPTP depleted killed off these guys dopamine cells by being taken up by a specific dopamine transporter (DAT) and wrecking the mitochondria inside (the powerhouse of the cell). This to me suggests that modafinil has had these protective effects by being a similar shaped molecule to this compound competing it out and getting and preventing its affects (this is my guess, I have not had access to the journal so it could be wrong).
So if modafinil is acting in a similar way to dopamine what does this mean in terms of adverse long term affects. As mentioned depletion of dopamine is the cause behind Parkinson’s disease ie rigidity. I notice with myself that I am more active whilst taking it, concurring with the expected opposite to parkinsons like symptoms. On the other hand excess dopamine is thought to be the cause behind schizophrenia, indeed most antipsychotic drugs block dopamine. This does not mean that buy taking it long term you are likely to develop it since it is mainly caused buy genetics. Merely this suggests that some of the reasons why dopamine causes schizophrenia may also affect a modafinil user, enhanced sensory responses and vigllance. Dopamine is a modulator and can enhance any active stimulus going through your brain.
I feel I am willing to take the risk by taking this drug, it improves my life and there may well turn out to be positive benefits long term but equally negative affects can not be rulled out. I trust the FDA, they license it at the moment for long term use in a couple of conditions so they can not be too wooried about it.
[COLOR=blue][COLOR=red]I am a modafinil user and would be interested to as to long term affects but I think at the moment it is very hard to tell.
