GEROVITAL (GH3) Articles (III)
Antidepressive Effect and Action of Gerovital-H3®
(The Treatment Of Cognitive Impairment)
by Mircea Dumitru M.D., Ph.D.
states and cognitive impairment in old people represent some of the
most important issues in our contemporary life. According to DSM-III-R,
even young people are suffering various forms of depression, their
frequency being from 3% to 6%, but in old people the incidence is
even greater occurring in 15% in men and 21% to 23% of women.
almost all other human cells divide in a continuing chain, nerve cells
do not multiply. Every day approximately 150,000 brain cells die and
as we grow older, even more die daily. Brain cells are intricately
connected in a very complicated network. While we lose many cells
every day, we have an enormous reserve of cells in our brain that
store information, facts and experiences. The impairment of the cognitive
function is the expression of the functional and structural events
that are changing with age: alterations of the neurotransmitter levels;
the decrease of proteins and DNA synthesis and the decrease of membrane
are involved in facilitating the acquisition of information and memorizing
facts. Among them, the cholinergic system plays a key role. The age
related cholinergic impairment goes through other neurotransmitters
producing additional effects on cognitive function (1).
have revealed that long-term memory is connected to the cortical protein
synthesis and short term-memory to the hippocampus protein synthesis
possible targets of aging metabolic change occur in the nervous system,
processes such as modifications of DNA, RNA and proteins, which in
turn affect learning and memory (4).
and Brain Cell Alterations
and its hydrolysis products PABA and DEAE follow the neurotransmitters
pathway. PABA represents the background of folic acid formation, through
which its co-enzymatic structure, [tetrahydrofolic acid], has an essential
roll in the pureness of pirimidine-tymine biosynthesis. Due to procaine's
interaction with the membrane phospholipids, Gerovital-H3® is
involved in the improvement of degenerative processes in old age.
indicates that Ca2+ regulation changes are constantly associated with
brain aging and malfunctioning cells that could be due to the structural
and functional capacity of the cellular membrane, Ca2+ connecting
proteins, or energy-dependant systems that regulate Ca2+.
various molecular systems that are regulating and maintaining the
calcic homeostasis represent the final mutual path for the age-related
brain changes (5). Gerovital-H3® interacts with various ionic
channels by modu1ating the inter-cellu1ar processes of Na+, K + and
Ca2+. By modu1ating the Ca2+ conductivity within the excitable biological
structures, Gerovital-H3® maintains the intracellular calcium
homeostasis. This is the pathway through which Gerovital-H3® restores
the hypocampic neurons normal excitability, counteracting their increasing
phenomena of the hyper polarization. The resu1ted ethanol amine of
the second stage of procaine hydrolysis is the forerunner of the phosphodiethylethanolamine
synthesis. Phosphodiethylethanolamine along with phosphatidylserine
and phosphatidylcholine represent the ce1lu1ar membrane's structural
phospholipids. As a resu1t of the consequent methylization, phosphotidilethanolamine
is converted into phosphatidylcholine and through a reversible reaction
with L-Serine creates phosphatidylserine (6).
the aging process, we see a decrease of the membrane phospholipids
synthesis with deep physiological consequences. Ethanol-amine from
Gerovital-H3®- plays a role in restoring the structure and the
physiological processes of the cell membrane.
data shows that under Gerovital-H3® treatment the level of the
learning rate is higher, with a better emotional adjustment and orientation
has been shown that the best performances of monastic retention are
of those groups treated with Gerovital-H3®, DEAE and PABA+EA (7)."
and Clinical Studies
and antidepressive drugs, (especially the tricyclic substances) in
elderly people is counter-indicated due to the common acetylcholinic
the group of MAO-I's medication (mono-amine oxidase inhibitors) a
new treatment appeared with better general tolerance and without side
effects- it was Gerovital-H3® (8, 9, 10, 11).
did the first double-blind study comparing the effects of Gerovital-H3®
administered i.m., versus Imipramine administered p.o. and versus
studied outpatients 60 years and older, who had mild depressive disorders
of global severity. This was determined by using a Clinical Global
Impression. The dosage of Imiprarnine treated patients during the
4-week treatment period showed a mean total dosage of 74,8 mg/day.
The dosage of patients on Gerovital-H3® during the 4-week period
of treatment showed a mean tota1 dosage of 2,022 mg.
Day 0 with Day 28 of all the variable measures in the Gerovita1 H3
treated group, the results indicated that the patients improved significantly
on Clinical Globa1 Impression, and on the Anxiety Status Inventory
and on the Self-rating Depression Scale (8). The results of this study
show that using Clinical Global Impression and the Zung Self Depression
Sca1e, the change scores obtained from ca1culating pre-treatment to
post-treatment differences prove Gerovital-H3® to be superior
to imipramine since the Gerovital-H3®/ placebo differences were
significantly different, while the imipramine/ placebo differences
and Gershon using a maximum tota1 dosage of 1,350 mg of Gerovita1-H3
reported improvement in depressive symptomatology of their senile-arteriosclerotic
patients studied (12). Ba1aceanu and al (13) in 1996 did a double-blind
study in order to point out the antidepressive effect of Gerovital-H3®,
to assess the clinical tolerance of the drug and the possible side
effects. After a geronto-psychological screening from 1443 old people,
and using DSM-III-R criteria, the authors selected 286 patients suffering
from various forms of depression. They excluded patients with a marked
decrease of visua1 and auditive acuity, severe pathology and depressive
patients who already took antidepressive treatments.
1 received Physiologica1 serum and Group 2 received Gerovital-H3®
as follows; for 10 days 1 i.m. via1 in the morning, and for 11 more
days 2 i.m. vials, one in the morning and one at noon. During the
treatment one patient with organic depressive syndrome and a1cohol-dependent
personality disorders presented psychiatric side effects, virulence,
irritability and harm pretending tendencies.
conclusion, the authors noted that the clinical tolerance was good.
The assessment of the depressive state intensity using psychological
methods proved statistically significant ameliorations after the treatment
with Gerovital-H3®. The cognitive performances were better at
the second examination in the group receiving Gerovital-H3® comparing
with the group receiving physiological serum.
Amine Oxidase (MAO) is mainly responsible for the degradation of biogenic
amines and a MAO inhibiting effect brings about an increase of biogenic
amines concentration at the synaptic level. It is known that Gerovital-H3®
is a selective and reversible inhibitor of MAO (14). Hrachovec showed
that Gerovital-H3 has an enhanced inhibiting action (87,4%) as compared
to procaine hydroch1oride (64.9%) on MAO (15).
a1so demonstrated that Gerovital-H3® is a MAO inhibitor (16).
These studies are particularly relevant in view of Robinson demonstrating
a relationship between aging, MAO levels and central amines (17).
Robinson found that MAO activity correlates highly with increasing
age when studied in human brain, plasma and platelets. Women were
found to have significantly higher mean platelet and plasma MAO activity
mechanisms of Gerovital-H3® action are possible, these include:
thyroxin-hydroxylasis activation through an alosteric effect determined
by ions influx and inhibition of synaptic uptake (18). We know that
repeated administration of MAO-I drugs depresses 5-HT 1 (the somato-dendritic
auto receptors of serotoninergic neurons) determining an inhibition
of synaptic occupation.
is also a cholinergic activator through its hydrolysis products- diethylaminoethanol
and ethanol amine, and can exert indirectly a modulating action on
the other systems of neuromediators, an action which has a certain
regional specificity. This assertion is based on the fact that there
is an extensive distribution of monoaminergic terminations on the
cholinergic neurons- the striatal cholinergic basal nuclear complex,
which suggests several anatomic and functional interactions between
these systems, interactions that often have double meaning (19).
in a fundamental study summarized the mechanisms of Gerovital-H3®
in depression (20):
Gerovital-H3® is a reversible and competitive inhibitor of MAO.
Gerovital-H3® may function as an antidepressant by modifying the
level of brain monoamines.
Compared with classic MAO-I, Gerovital-H3® is quite selective
in inhibiting the oxidative desamination of certain important brain
Due to the inhibition of Gerovital-H3® on the oxidative desamination
of liver Tyramine and Tryptamine, the normal physiological function
of liver MAO to inactivate excess amount of ingested or endogenously
present toxic amines is not impaired, thereby eliminating the "hypertensive
crisis" so typical of other MAO inhibitors.
Yau concluded that, in addition to being an efficacious drug in the
treatment of depression, Gerovital-H3® seems to have some additional
advantages in terms of its pharmacological effects and increased safety.
data proves that Gerovital-H3® is not on1y an effective antidepressant
treatment, but it also stimulates cognitive functions, loco-motor
activity and improves emotional stability.
determines a central nervous system functional amelioration by the
active neuro-mediating and balances equilibrium among neurotransmitters.
Due to the inhibition of the generation of the super oxide radical,
Gerovital-H3® is an anti-oxidant, a potent free radical quencher.
is not only useful to treat depressive disorders in adults and elderly
people but also to prevent them. Gerovital-H3® treatment is indicated
to prevent degenerative processes and to retard the ageing process
and to help prevent various forms of depression frequently associated
with them. The incidence of depression in the elderly having utilized
a long-term Gerovital-H3® treatment is far lower than in similar
groups without any treatment.
treatment of chronic diseases, the ageing process and depression consists
of 4 courses of 12 injections and 4 courses of 24 pills during one
year; one course of 12 injections over 4 weeks (4 injections per week),
a 4-week break then one course of 24 pills over 12 days (one pill
twice daily between meals), a 2-week break and then the cycle is resumed.
from the age of 40, the prophylactic treatment with pills on1y is
recommended in a series of 25 tablets during the first 12 days, with
an interval of 2 months; 1st day, one tablet/day, 2 hours after breakfast,
increasing to the 12th day when 2 tablets per day are taken (2 hours
after meals-10 AM and 4PM). There should be a series of 5 treatment
courses in a year, which shou1d be increased to 6 per year for people
over the age of 65.
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