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Re: does selegiline really mitigate DAergic cell l

Posted by linkadge on June 15, 2008, at 18:32:51

In reply to Re: does selegiline really mitigate DAergic cell l undopaminergic, posted by SLS on June 15, 2008, at 5:31:51

The neuroproective effects of selegiline are likely independant of its MAO-B inhibitory effects. There are a several other MAO-B inhibitors which do not share the neuroprotective effects of selegiline. Selegiline has some intrinsic antioxidant regulatory effects which may be more responsible for the neuroprotective effects. The amphetamine metabolites of selegiline may detract from its neurotrotective effects. Along these lines, Rasigiline might be preferable as it is devoid of amphetamine metabolites.

One thing I found interesting was that MAO-B inhbitors like selegiline appear to upregulate the dopamine transporter, perhaps as a compensatory pathway for dopamine metabolism. I don't know how this figures into its ability to protect against the neurotoxin MPTP. I would have thought that increased activity of DAT would enhance the entry toxins like MPTP into cells.

Selegiline is not entirely safe. In Parkinson's there is a risk of cardiovascular complications with higher doses. It can be activating and highly anxiogenic for some. Selegiline can really help some forms of depression (perhaps associated with low PEA), while it can exaserbate other forms of depression. I heard a case report of it exaserbating psychotic depression.

While it is clear that MAO-B metabolizes PEA, there is some dispute of the extend to which MAO-B actually metabolizes dopamine.

I think agents like melatonin are probably a safer way to get similar neuroprotective effects. I.e. I wouldn't use selegline purely as a neuroprotectant.





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