Posted by PeterJ on May 16, 2000, at 18:58:50
In reply to Re: Amineptine substitute? Scott, COMT inhibitor, posted by SLS on May 16, 2000, at 7:22:58
I can't always post as much as I'd like when I'm
feeling fatigued, but here are some further
observations on dopamine that may be helpful.1. It's not too clear what the difference between
releasers and uptake inhibitors is clinically.
Amphetamine does both. Cocaine inhibits DA uptake
but does not cause release. Both have very
similar behavioral effects.
The mechanism of amineptine depend on
which lab you believe. I've seen a studies that
say it increases DA release and others that say
it only inhibits uptake. I'm inclined to think
it is an uptake inhibitor only, based on its
large tricylic structure.
BTW, the dopamine transporter acts like a shuttle
that goes back and forth across the cell membrane.
When it crosses it can take a molecule of
dopamine with it. (Imagine one of those clotheslines
strung btween two buildings with a pulley. The
dopamine transporter is like a basket on the line.)
It can shuttle dopamine into or out of the cell,
depending on the situation.
If you give amphetamine, it binds to the shuttle
on the outside of the cell. The shuttle then
crosses over to the inside face of the membrane,
taking the amphetamine with it. The amphetamine
is released inside. Then some dopamine binds to the
now empty transporter and it is shuttled to the outside
of the cell.
A pure uptake inhibitor will bind to
the tranporter when it is on the outside surface of the
cell and put it in such a conformation that it is stuck
there and cannot cross back over. Thus it cannot shuttle
dopamine into the cell.
2. Mazindol has been studied in a PET study of
human subjects. The study intended to explore
its use as a treatment for cocaine addiction.
Typical doses of mazindol only
bound a very small percent of DA receptors. It
was felt that doses high enough to inhibit
DA receptors would have excessive side effects.
Mazindol seems to be about 20X more potent
at inhibiting NE uptake.
It has been reported to relieve
depression in a few cases, but that may
be due to its NE effects as much as its DA
effects.3.Long term l-deprenyl leads to the accumulation
of some unknown substances which block DA uptake. Thus
it may enhance DA activity both by MAO inhibition and
indirectly by uptake inhibition.4. St. John's Wort may have mild dopaminergic
effects.5. Niacinamide in high doses (500mg-3gms) may help somewhat
in dopamine depletion by stimulants. NADH, which
you can get also get OTC from some pharmacies
may also help.6. COMT inhibitors have theoretical interest, but
limited clinical experience in depression. Details
were discussed in another thread.7. Initial enhancement by many substances of
dopamine activity often results in only short-
lived benefits. Dr. Baron Shopsin, who
studied several dopamine drugs clinically in the
70s and 80s found this to be their achilles heel.8. Amineptine is one of the few antidepressants
to increase REM sleep. Bupropion is another, and
it may also have mild DA effects. It might be
worth trying.9. Direct DA agonists like piribidel, bromocriptine,
pramipexole, etc., may also help.Peter
poster:PeterJ
thread:33419
URL: http://www.dr-bob.org/babble/20000508/msgs/33691.html