© 1991-2014 Jerry Emanuelson
DEPRENYL
Deprenyl was developed by
Dr. Joseph Knoll
of Semmelweis University in Budapest, Hungary during the early 1960's
for possible use as an anti-depressant. The medicine initially showed
limited usefulness as a treatment for depression; but more than a decade
after its initial development, deprenyl was found to be an effective
treatment for Parkinson's Disease
.
Deprenyl acts on an important chemical in the brain called dopamine. Dopamine is manufactured in the brain from two amino
acids that occur naturally in foods: phenylalanine and tyrosine.
To function properly, the human body requires a multitude of
chemicals in well-regulated quantities. For most of these necessary
chemicals, the human body has one biological process to manufacture the
chemical and another process to break it down. Dopamine is broken down
in the brain by a chemical called MAO-B. It is important for good
health that the manufacture of dopamine from amino acids and the
destruction of dopamine by MAO-B is kept in balance.
If the
destruction of dopamine by MAO-B occurs at a faster rate than its
production from the amino acids, the brain cells that use dopamine will
die. The loss of dopamine and the resulting brain damage can cause
tremors, rigid muscles, loss of
coordination, weakness and death.
Beginning at about age 45, the destruction of dopamine in the
brain by MAO-B begins increasing. The amount of dopamine in the
typical about human brain begins decreasing by 13 percent every decade.
In about 0.5 percent of the population, the decrease in dopamine
takes place much more rapidly than the usual 13 percent every ten
years. When the dopamine content drops to about 30 percent of normal,
these individuals develop the tremors and rigid muscles that are typical
of Parkinson's Disease. Parkinson's patients typically experience a
decrease in dopamine levels of 30 percent to 90 percent every ten
years. Death usually occurs in Parkinson's patients about the time
their brain dopamine content falls to 10 percent of normal.
In the past, the most popular treatment for Parkinson's Disease
has been L-Dopa. L-Dopa is an amino acid that is not present in the
ordinary human diet. The brain can make dopamine much more easily from
L-Dopa than from the tyrosine and phenylalanine usually
obtained from the human diet.
Deprenyl attacks the other end of the dopamine-preservation process by inhibiting the action of the MAO-B.
During the 1980's, deprenyl, either alone or in combination with
L-Dopa, was the most effective known drug treatment for Parkinson's
Disease.
Some of the enthusiasm for using deprenyl in Parkinson's Disease
has been dampened after it was discovered that the dosage levels used
were often too large, and that determining and maintaining the proper
dosage in a clinical setting was more difficult that was first thought.
Dr. Knoll claims that deprenyl is also effective in
preventing Parkinson's Disease.
According to Dr. Knoll, deprenyl has "proved to be a safe drug in
man. Neither hypertensive reactions nor the need for special
dietary care were ever encountered during long-term (2-8 years) daily
administration of the drug." Knoll said that the lethal dose
of the drug is more than 1000 times its effective daily dose. Knoll
called this safety margin "remarkable."
Dr. Knoll also said that deprenyl is an effective treatment for
aging.
The average life span of the deprenyl-treated rats was 192
weeks. The researchers considered this to be particularly remarkable
since
the maximum life span of that strain of laboratory rats is considered to
be 182 weeks.
According to Dr. Knoll, similar life-extending results could be
expected in humans. The biological processes deprenyl acts upon to
cause its life span extending effects in rats are well-known; and there
is general agreement among scientists that deprenyl acts on
the same processes in humans.
Dr. Knoll points to the normal decrease in dopamine in the aging
brain as an indication of how deprenyl works to increase life span.
He said that it is no coincidence that even the healthiest humans die at
about the time the dopamine content of their brain drops below the
critical 30 percent level. According to our present knowledge, the
neurons (brain cells) that use dopamine are the most rapidly aging
neurons in the human brain.
| AGE
45
55
65
75
85
95
105
115
125 |
DOPAMINE CONTENT
100 percent
87 percent
74 percent
61 percent
48 percent
35 percent
22 percent
11 percent
0
|
Deprenyl is
broken down in the body to amphetamine and methamphetamine. London
researcher G. P. Reynolds and his associates reported in a British
medical journal that even in the larger doses used in Parkinson's
Disease, deprenyl is "unlikely to produce any marked degree of central
amphetamine-like action."
The amphetamine and the methamphetamine breakdown products of
deprenyl can show up in urine, though.
In 1987, Dr. Shulman was 62 years-old and so severely afflicted with
Parkinson's Disease that he was hardly able to move without help. He
obtained some deprenyl from Europe after hearing about the drug from a
neurologist.
In Longevity magazine, Dr. Shulman is quoted as saying that
"within 24 hours of taking the drug, I stopped shaking and shuffling,
returned to normal, and went back to work."
Dangers of Deprenyl
One of several causes of impaired mental development in Down's
syndrome is the excess production of SOD. The excess SOD destroys some
types of free radicals but, in the process, SOD produces more of the
dangerous hydroxyl radical than the other antioxidant systems can
handle. There is a possibility that deprenyl, even at low doses, could
produce some of the same kind of damage.
Obviously, if we could re-balance the antioxidant systems, the
excess SOD activity could be turned from a problem to an advantage. It
will be years before we know the effect of long-term low-dose deprenyl
in humans. In the meantime, here are some things for anyone
contemplating low-dose deprenyl for life extension to consider:
- The three major natural antioxidant systems in the body are SOD,
catalase, and glutathione peroxidase. Deprenyl raises SOD activity
markedly, catalase activity slightly, and glutathione peroxidase
activity none at all. The nutritional supplement N-Acetyl-Cysteine
(NAC) raises glutathione peroxidase levels and should help to re-balance
the body's natural antioxidant system in those using deprenyl.
- It is probably unwise for anyone to use deprenyl without
rather large doses of supplementary antioxidant vitamins, especially
vitamins C and E.
- The increased SOD activity induced by deprenyl is
greater in females than males. The lifespan studies with deprenyl that
produced positive results in animals were always done with male
animals. Female animals did not have positive results in lifespan
studies. The ideal dose of deprenyl in women appears to be less than
the ideal dose for men. The use of supplementary antioxidants in women
taking deprenyl is correspondingly more important than for men taking
deprenyl.
Dosage for Life Extension.
The optimum dose of deprenyl for life extension purposes is
unknown. Extrapolation from animal experiments would indicate that it
is about 5 mg. every other day. Some scientists, though, have
suggested that people in their forties begin with 5 mg. per week and
gradually increase to about 5 mg. per day by the time they reach their
seventies. Another complicating factor is that the early deprenyl
experiments were done only with male animals. A recent study using
male and female rats indicated that the optimal dose for females is much
smaller than the optimal dose for males. Until more research is done,
it may be prudent for healthy women under 70 to limit their dosage to 5
mg. per week.
The half-life of deprenyl in the body is only a few hours; but once it enters the brain, its effects are very long-lasting.
The half-life of MAO-B inhibition in humans has been measured to be about 40 days, therefore, deprenyl probably need not be taken daily by persons who do not have a neurological disease.
The successful life extension experiments with deprenyl have
been done in rodents, where the half-life of MAO-B inhibition due to
deprenyl is 8 to 11 days, as opposed to 40 days in humans. This
indicates that life extension doses extrapolated from rat studies may be
4 to 5 times too high for humans.
(In the study where the half-life of MAO-B inhibition was
measured in humans, it was about 38 days in the normal subjects and 43
days for patients with early Parkinson's disease. The normal subjects
were four non-smoking males ages 62 to 69. The Parkinson's patients
were 2 males and 2 females ages 62-70.)
