INHIBITING THE INHIBITORS By Joe Bruman Chapter I of IV
(The Entacapone Story)
Introduction:
I study the science aspects of PD not so much to compete with
doctors as to appreciate the kind and amount of information that
guides their decisions. Modern drug therapy is so complicated
that I compiled this little summary to sort it all out. To
avoid email overload, I'll post one page of this per day. J.R.B.
Amino Acids:
Amino acids comprise a large group of organic compounds that
contain both an amino (NH3) radical and a carboxyl (COOH)
radical. (In the diagrammatic formula, carboxyl doesn't look
like that, but instead: O
//
- C
\
O - H
About 80 amino acids are found in nature, but only 20 are
necessary to humans. Some of those are made by the liver,
but 11 others, called "essential" amino acids, must be supplied
in food or diet supplements.
Dopamine:
Dopamine is made by part of the brain called the substantia
nigra, whose neuron cells project to other brain entities such
as the basal ganglia, where it acts as a neurotransmitter to
regulate posture, balance, and movement in the voluntary muscle
system. It's generally held that Parkinson's Disease results
directly, if not entirely, from progressive failure of the
substantia nigra, and the main objective of drug treatment in
PD is to replace or mimic the missing dopamine. Although dopamine
is made elsewhere in the body, particularly in the adrenal gland
attached to each kidney, even when PD attacks the substantia
nigra, that doesn't help because the blood capillaries in the
brain have a special filter system (the "blood-brain barrier")
that prevents entry of some substances that might be harmful to
the vulnerable brain, and dopamine is one of those excluded. PD
effects certainly extend beyond those controlled by the central
nervous system; for example, constipation is mediated by
autonomic peripheral nerve centers of the gut, and how it can be
a common PD symptom isn't entirely clear.
Levodopa:
The amino acid levodopa, also called dopa or L-dopa, is the
immediate chemical precursor of dopamine. Dopa is the acronym
for DihydrOxyPhenylAlanine, after the characteristic groups
that can be seen in its diagrammatic chemical formula. Levodopa
is converted to dopamine by the enzyme dopa-decarboxylase, which
replaces its carboxyl group with a single hydrogen atom. (The
name of an enzyme ending in -ase is supposed to give a clue about
what the enzyme does.) Although the levodopa molecule is bigger
than dopamine, it does cross the blood-brain barrier, so drug
researchers selected it as a means for getting dopamine into the
brain via the mouth. But in the long path from mouth to brain,
unless protected, most of the levodopa would be converted
prematurely to dopamine and wasted, so a lot of levodopa would
be needed for a little to reach the brain, and levodopa alone is
intolerably nauseous to most people.
--
J. R. Bruman (818) 789-3694
3527 Cody Road
Sherman Oaks, CA 91403-5013
