Note: Descriptions are shown in the official language in which they were submitted.
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Composition com rising L-carnitine or an alkanoyl L-carnitine and
NADH andlor NADPH
The present invention relates to a composition which exerts an action
both on the metabolism and energy performance of skeletal muscle and
on the regulation of muscle movement and co-ordination at central
level through potentiation of effects at both peripheral muscle and
central nervous system level. Accordingly, the composition may take
the form and exert the action of a dietary supplement or of an actual
medicine, depending upon the support or preventive action, or the
strictly therapeutic action, which the composition is intended to exert
in relation to the particular individuals it is to be used in.
In particular, as a dietary supplement or preventive agent, the
composition of the invention is particularly suitable both for
facilitating adaptation of skeletal muscle in individuals engaging in
intense, prolonged physical activity and to combat the sensation of
muscle fatigue and exhaustion experienced by. asthenic subjects even
in the total absence of any form of more or Iess intense physical
activity.
Anyone who engages in sports activities, whether professionally or as
an amateur, wishes to achieve in a short space of time, and then
maintain for as long as possible, the maximum degree of adaptation of
the skeletal muscles to the ability to sustain prolonged periods of
intense physical activity. The quest for this optimal state of fitness
may lead to the inappropriate use of drugs, particularly steroids. It is
well known that such drugs can enhance protein synthesis and
consequently potentiate the growth of muscle mass to a greater extent
than can be achieved with training and diet. The .use of these drugs is,
however, both illegal and unquestionably harmful when practised in
professional sport.
Clearly, then, the only way to achieve the above-mentioned objective
properly consists in undergoing appropriate training programs
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combined with suitable diets, potentiated through the addition of
appropriate dietary supplements.
What is meant here by the term "asthenia" is the diffuse set of aspecific
symptoms typical of the stressful life conditions currently prevailing
particularly in the major conurbations and built-up areas and
involving a vast population, largely regardless of factors relating to age
and social status, characterised by a lack or loss of muscular strength,
with easy fatigability and inadequate reaction to stimuli.
When used as a strictly therapeutic agent, one particular application of
the composition of the invention is in the treatment of chronic fatigue
syndrome and Parkinson's disease and of a syndrome similar to
idiopathic parkinsonism, induced by the administration of illicit drugs.
Chronic fatigue syndrome (CFS}, officially described for the first time
in 19$8 in Annals of Internal Medicine, is a disease characterised by a
degree of tiredness not explained by any known cause, often much
more intense than that encountered in very serious diseases, such as
tumours and AIDS, and debilitating to the extent of causing a more
than 50% reduction in working activity and normal social relations,
lasting more than 6 months.
According to the criteria outlined in Annals of Internal Medicine
(December 1994} for diagnosing CFS, the patient must present at least
four of the following eight symptoms persistently over a period of 6
months:
1. neuropsychological disorders such as memory loss, excessive
irritability, mental confusion, difficulty with thinking and
concentrating;
2. pharyngitis;
3. palpable, tender cervical or axillary lymph glands;
4. muscle pain;
5. migratory arthralgia without, however, any swelling of the joints;
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6. generalised headache different in type, characteristics and severity
from any headaches the patient experienced prior to the disease;
7. sleep disorders, characterised by insomnia or hypersomnia or
drowsiness;
8. generalised fatigability and malaise lasting for 24 hr or more after
physical activities at levels which were easily tolerated previously.
It is well known that, though Parkinson's disease is generally regarded
as an idiopathic condition, the symptoms of parkinsonism can result
from the abuse of drugs such as phenothiazine, butyrophenones and
reserpine. More recently, parkinsonism has been studied in drug
abusers injecting themselves with compounds similar to meperidine,
the abusive synthesis of which had produced MPTP and MPPP.
In fact, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP or
NMPTP) and 1-methyl-4-phenyl-propoxy-piperidine (MPPP) selectively
destroy the dopaminergic neurones in the substantaa nigra and induce
a syndrome both in man and in primates other than man which is
entirely similar to idiopathic Parkinson's disease as regards its clinical,
pathological and biochemical aspects and its pharmacological
responses.
The similarity between idiopathic Parkinson's disease and MPTP-
induced parkinsonism is so great that it has been postulated (Burns et
al.: The neurotoxicity of I-methyl-4-phenyl-1,2,3.6-tetrahydropyridine
in the monkey and man. Can. J. Neur. Sci., 11, n. 1 (supplement), 166-
168, February 1984) that this induced parkinsonism "may constitute
more than a model. MPTP-induced parkinsonism suggests a putative
toxic cause for Parkinson's disease".
The therapy of choice for the management of Parkinsan's disease is
currently based on the administration of levo-dopa (L-dopa), the
metabolic precursor of dopamine, which in itself is incapable of
crossing the blood-brain barrier.
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Since levo-dopa is extensively metabolised before it is able to xeach the
sites of action in the brain, it should be administered at very high
doses. L-dopa is thus administered in combination with carbidopa, an
inhibitor of dopa decarboxylase which prevents the systemic
metabolism of levo-dopa before the latter reaches the brain.
When levo-dopa is administered alone, side effects may occur such as
anorexia, nausea and vomiting and orthostatic hypotension, which are,
however, substantially relieved as soon as carbidopa is administered as
well.
After a few months of therapy with L-dopa, however, even when
combined with the decarboxylation inhibitor, other very troublesome
side effects are possible and frequent: dyskinetic movements of the
face, trunk and limbs. The onset of such movements, in most cases;
indicates that the drug dosage has reached a critical threshold which
must not be exceeded.
There is therefore a strongly perceived need for a support/preventive/
therapeutic agent which, as a result of its efficacy; substantial non-
toxicity and lack of side effects, can be safely used by such a broad
range of users both in cases simply requiring an appropriate food
supplement and at initial onset of symptoms in the above-mentioned
pathological conditions.
These multiple goals - to produce a support, preventive and strictly
therapeutic agent - are achieved by the composition of the invention,
which, as will be described in detail here below, consists in a new
combination comprising as its basic ingredients L-carnitine or a lower
C2-C6 alkanoyl-L-carnitine or their pharmacologically acceptable salts
and nicotinamide adenine dinucleotide (NADH) or a NADH precursor
and/or nicotinamide adenine dinucleotide phosphate, reduced form
(NADPH).
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Over the decades elapsing since the basic discovery (Fritz LB.: The
metabolic consequences of the effects of carnitine on long-chain fatty
acid oxidation. Edited by F.C. Gran, New York, Academic Press, 1968,
pp. 39-63) that L-carnitine is unique in performing a vital physiological
role as a vector of long-chain fatty acids across the internal mito-
chondria) membrane into the mitochondria) matrix, which is the site of
their oxidation, and since a primary deficiency of L-carnitine was first
recognised (Engel and Angelini, Science, 1973; 179: 899-902) as the
cause of a severe, sometimes fatal, though raze, form of myopathy
(lipid storage myopathy), there have been enormous advances in our
knowledge of the pathological consequences of primary and secondary
L-carnitine deficiencies and, conversely, of the therapeutic and
nutritional value of an exogenous supply of L-carnitine.
Carnitine is present in ali biological tissues in relatively high
concentrations as free carnitine and in lower concentrations in the
form of acyl carnitines which are metabolic products of the reversible
reaction:
acyl CoA + carnitine ~ acyl caxnitine + CoASH
catalysed by three groups of enzymes, i.e. the transferases which
mainly distinguish themselves by virtue of their specificity for reagent
substrates: the carnitine acetyl transferase (CAT) group whose
substrate are the short-chain acyl groups (such as acetyl and
propionyl); the carnitine octanoyl transferase (COT) group whose
substrate comprises the medium-chain acyl groups; and the carnitine
palmitoyl transferase (CPT) group whose substrate comprises the long-
chain acyl groups.
The important role of carnitine in intermediate metabolism, with
particular reference to its limited biosynthesis, serves to explain how a
carnitine deficiency may occur as a secondary event in various
pathological functions involving different organs and systems. The
broadening of the clinical spectrum is reflected in the increasing
number of therapeutic opportunities related to the efficacy of this
natural compound; the whole scope and range of this efficacy was
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revealed when it was observed that L-carnitine replacement therapy
dramatically reverses the clinical picture in patients suffering from
lipid storage myopathy. The Food and Drug Administration (FDA)
have not only accorded L-carnitine the status of an "orphan drug", but
have also included it in their list of "life-saving" drugs.
The advances in our knowledge of the pathological implications of
primary and secondary carnitine deficiency have been accompanied by
a very substantial upsurge in scientific and patent publications mainly
focusing on L-carnitine and, to a considerably lesser extent, on some of
the acyl carnitines.
Confining ourselves to a partial survey of the patent situation, the use
of L-carnitine has been proposed in the cardiovascular field fox the
treatment of cardiac axrhythmias and congestive heart failure (LTS
4,656,191), myocardial ischaemia and myocardial anoxia (US
4,649,159); in the field of disorders of Iipid metabolism, for the
treatment of hyperlipidaemias and hyperlipoproteinaemias (US
4,315,944) and for normalising an abnormal HDL:LDL-VLDL ratio (US
4,255,449}; in the field of total parenteral nutrition (US 4,254,147 and
US 4,320,145); in nephrology, to counter myasthenia and onset of
muscle cramps caused by carnitine losses in dialysis fluid in chronic
uraemic patients undergoing regular haemodialytic treatment (LTS
4,272,549); to counter the toxic effects induced by anticancer agents
such as adriamycin (US 4,400,371 and US 4,713,370} and by
halogenated anaesthetics such as halothane (LTS 4,780,308); in the
treatment of venous stasis (LTS 4,415,589); in countering the
deterioration of a number of biochemical and behavioural parameters
in elderly subjects (US 4,474,812); for normalising triglyceride and
tumor necrosis factor (TNF-a) levels in patients with AIDS and in
asymptomatic HIV-positive patients (US 5,631,288).
The use of L-carnitine has also been proposed in combination with
other active ingredients, such as the L-caxnitine coenzyme Q10
combination with a broad spectrum of metabolic/anti-atherosclerotic
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action {US 4,599,232).
As regards the alkanoyl L-carnitines, the use of acetyl L-carnitine is
known for the treatment of central nervous system diseases,
particularly Alzheimer's disease (US 4,346,10?) and for the treatment
of diabetic neuropathy (US 4,751,242), whereas propionyl L-carnitine
has been proposed for the treatment of peripheral vasculopathy (US
4,343,816) and congestive heart failure (US 4,194,006).
Equally complex is the activity exerted by the coenzyme nicotinamide
adenine dinucleotide (NADH) whose role at the energy level is well
known.
Its function in the respiratory chain is essential for the transport of
electrons in the mitochondrial system and in the formation of ATP.
Two NADH dehydrogenases have been isolated from the internal
mitochondrial matrix. The one with the lower molecular weight (M.W.
78,000), which is probably a subunit of the larger complex (M.W. above
300,000) is regarded as the naturally occurring functional form of the
system.
The various complexes located in the internal mitochondrial membrane
constitute a chain of oxidative systems going under the name of the
cytochrome and Coenzyme Q10 chain, allowing the electrons to be
transported from a lower- to a higher-potential system with the use of
oxygen and formation of ATP. It is, in fact, from the respiratory chain
that the oxidative phosphorylation derives which leads from NADH to
the production of ATP.
NADH, along with the cytochrome and Coenzyme fq,110 complexes, are
the elements necessary for the transformation of energy to ATP and
the NADH to be found at the start of this chain is the main
conditioning element in this process.
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The enzymatic function of NADH is not mexely detectable in the
energy-type reaction for the formation of ATP, but NADH has also
recently been shown to act as a coenzyme necessary for
quinodihydroxy-pteridine reductase (DHPR) to proceed with the
biosynthesis of H4-biopterin.
The possibility of stimulating the biosynthesis of H4-biopterin and of
increasing its concentration in the brain was recently proposed as a
way of increasing L-dopa and thus dopamine which present
deficiencies in diseases such as parkinsonism, these deficiencies being
regarded as underlying the parkinsonian neuropathy. Whereas L-dopa
can act as a precursor of dopamine and thus transform itself
metabolically into this latter substance, the same does not happen in
the case of tyrosine, which can also be regarded as a precursor capable
of leading to the formation of L-dopa, without the presence of tyrosine
hydroxylase. A reduction in this enzyme has, in fact, been found at the
level of the substc~ntiac nigra of parkinsonian subjects. A reduction in
hydroxytyrosine would, moreover, be accompanied a powerful
reduction in H4-biopterin, a coenzyme necessary for the synthesis of
hydroxytyrosine. Since H4-biopterin does not cross the blood-brain
barrier and the direct administration of H4-biopterin is therefore of no
avail, it appeared to be useful, in contrast, to resort to stimulation of
the formation of H4-biopterin by administering the coenzyme
necessary for the activity of quinodihydroxy-pteridine reductase
(DHPR) for the formation of H4-biopterin, a function which is known to
be performed by NADH. Administration of NADH therefore activates
DHPR leading to the formation of the H4-biopterin necessary, in turn,
for activating tyrosine hydroxylase so as to achieve the neosynthesis of
dopa.
Clinical trials based on intravenous administration of NADH to
subjects suffering from Parkinson's disease have confirmed the validity
of the. theoretical assumptions outlined here above, showing a
significant improvement in Parkinson's symptoms in subjects thus
treated.
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Largely comparable results have been achieved with oral adminis-
tration of NADH, taking care to administer it using delayed-release
gastrointestinal capsules so as to avoid the acid milieu of the stomach
which would lead to a rapid reduction in NADH levels.
Clinical improvements in Alzheimer's disease and in chronic fatigue
syndrome (CFS) have also been reported with NADH administration
(Birkmayer J.G., Annals Clin. Lb. Sci., 26, 1 1996).
On the basis of the characteristics of the compounds described above,
the possibility of interaction between them was assessed by means of a
series of tests performed on combinations of L-carnitine or its alkanoyl
derivatives and NADH and/or NADPH. By means of the tests
performed on these new combinations, a surprising, unexpected
synergistic interaction was observed between the components of the
combinations, which was thoroughly unpredictable on the basis of our
pharmacological knowledge of L-carnitine or its alkanoyl derivatives
and NADH and NADPH.
The composition of the invention comprises the following components
in combination:
(a) L-carnitine or an alkanoyl L-carnitine in which the straight- or
branched-chain alkanoyl group has 2-8, and preferably 2-6 carbon
atoms, or one of their pharmacologically acceptable salts;
(b) NADH or a NADH precursor andlor NADPH; and
(c) a pharmacologically acceptable excipient.
Preferably, the NADH precursor is nicotinamide.
The weight-to-weight ratio of (a) to (b) generally ranges from 1:0.01 to
1:1, and should preferably range from 1:0.05 to 1:0.5; for example, the
weight-to-weight ratio may be 1:0.1.
The alkanoyl L-carnitine should preferably be selected from the group
comprising acetyl L-carnitine, propionyl L-carnitine, butyryl L-
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carnitine, valeryl L-carnitine and isovaleryl L-carnitine. Acetyl L-
carnitine and propionyl L-carnitine are particularly preferred.
For the purposes of the present invention, what is meant by L-
carnitine, acetyl L-carnitine, propionyl L-carnitine and isovaleryl L-
carnitine is these compounds in the form of inner salts.
What is meant by pharmacologically acceptable salt of L-carnitine or of
an alkanoyl L-carnitine is any salt of these with an acid that does not
give rise to unwanted toxic or side effects. These acids are well known
to pharmacologists and to experts in pharmacy.
Non-limiting examples of such salts, are: chloride; bromide; iodide;
aspartate, acid aspartate; citrate, acid citrate; tartrate; phosphate, acid
phosphate; fumarate, acid fumarate; glycerophosphate; glucose
phosphate; lactate; maleate, acid maleate; orotate; oxalate; acid
oxalate; sulphate, acid sulphate; trichloroacetate; trifluoroacetate and
methane sulphonate.
A list of FDA-approved pharmacologically acceptable salts is to be
found in Int. J. Phocrm. 33, {1986), 201-217, which is incorporated
herein by reference.
The composition of the invention may further comprise vitamins,
coenzymes, mineral substances and antioxidants.
In unit dosage form, the compositions of the invention comprise, for
instance, 100-500 mg of (a) L-carnitine or alkanoyl L-carnitine or an
equivalent amount of one of their pharmacologically acceptable salts
and a quantity by weight of (b) NADH or NADPH such that the
weight-to-weight ratio (a):( b) ranges from 1:0.01 to 1:1, and preferably
from 1:0.02 and 1:0.2.
Reference will be made here below, for the sake of simplicity, only to
the combination of L-carnitine and NADH, it being understood,
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however, that combinations of L-carnitine and NADPH or of the above-
mentioned alkanoyl L-carnitines and NADH andlor NADPH are
equally effective, fully achieving the objectives of the present invention.
Toxicology tests
Both carnitine and NADH are known to possess only limited toxicity
and good tolerability. These favourable characteristics were confirmed
by intravenously administering both to rats and to mice combinations
of up to 100 mg/kg of L-carnitine and 5 mg/kg of NADH. In prolonged
(30-day) , toxicity tests, the oral administration of a combination of 250
mg/kg of L-carnitine and 10 mg of NADH was well tolerated and
produced no evidence either of mortality or of toxicity or intolerance in
the treated animals. Blood-chemistry and histological investigations
performed in various organs at the end of txeatment revealed no
abnormalities as compared to control animals, thus confirming the
good tolerability of the combination studied.
Tests on increase in muscle enzymes after prolon~aed exercise
To assess the effect of carnitine and NADH as well as of a combination
of the two on the concentration of mitochondrial enzymes involved in
muscular exercise, tests were carried out to establish whether the
activity of these mitochondrial enzymes in the gastrocnemius muscle of
rats subjected to prolonged muscular exercise could be increased as
compaxed to control animals in response to the greater energy demand
required by prolonged muscular effort. To this end a group of Wistar
rats was subjected to muscle training by placing them on a R,otaroid
apparatus (Basile, Como, Italy) at a rate of 20 mlmin for 120 min every
day (Benzi G., J. Appl. Physiol., 38, 565, 1975). Muscle enzyme activity
was assessed after seven or after thirty days' training following
isolation and homogenising of the gastrocnemius muscle of each rat
(Oscai L.B., J. Biol. Med., 245, 6968, 1971}. The enzymes assessed were
citrate synthetase, isocitrate dehydrogenase and succinate dehydro-
genase.
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The results obtained in this test demonstrated that the combination of
carnitine and NADH was capable of inducing a very significant
increase in enzyme activity after only seven days of training, whereas
at this observation time no changes induced by either caxnitine or
NADH alone were detected as compared to controls.
The strong synergistic effect of these two products was even more
marked after thirty days' training.
Days' Citrate Isocitrate Succinate
Treatment Training synthetase dehydrogenasedehydrogenase
Controls 0 20.911.4 2.25*0,31 3.7010,22
Controls ? 22.1*1.6 2.30*0.20 3.9010.19
Controls 30 29.912.1 3.33*0.20 5.2010.30
Carnitine 250 0 20.8*0.95 3.0510.19 3.3510.35
mg/kg
Carnitine 250 ? 22.6*1.9 2.8510.31 3:85*0.45
mg/lcg
Carnitine 250 30 30.1*0.95 2.98*0.16 4.9010.33
mg/kg
NADH 10 mg/kg 0 21.5*1.4 2.3510.29 3.60*0.21
NADH 10 mg/kg ? 30.512.5 3.6510.55 4.1510.45
NADH 10 mg/kg 30 33.6*2.1 3.5510.36 5.4010.45
Carnitine 250
mg/kg +
NADH 10 mg/kg 0 21.411.9 2.15*0.18 3.80*0.22
Carnitine 250
mg/kg +
NADH 10 mg/kg 7 47.?*3.92 5.1*0.29 7.15*0.30
Carnitine 250
mg/icg +
NADH 10 mg/kg 30 ?5.9*3.51 6.310.5 9.2510.65
(*) Enzymatic activity is expressed as umol of substrate used per minlg tissue
weight
Tests on increase in rabbit papillar~muscle ATF concentrations_after
hypoxia
These tests were used to assess whether L-caxnitine and NADH or a
combination of the two were capable of preserving ATP concentrations
of rabbit heart papillary muscle after subjecting the rabbit to hypoxia,
which is known to lead to depletion of this energy compound. The tests
were conducted on New Zealand rabbits which received intravenous
injections of both L-carnitine (100 mg/kg) and NADH (10 mg/kg) alone,
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as well as of the two substances in combination, every day for three
consecutive days.
Another group of animals served as a control group receiving no
treatment. At the end of the third day of treatment all animals were
sacrificed, their hearts were extracted and sections of papillary muscle
measuring 1 mm in diameter and 4.5 mm in thickness were isolated.
The tissues thus isolated were perfused in a thermostatic bath with a
100% saturated O2 solution. The experimental hypoxia was then
produced by introducing 100°/ N2 in the bath in place of 02. The ATP
content of the papillary muscle was analysed using the method
described by Strehler B.L. (Strehler B.L., Methods in Enzymology III.
New York. Acad. Press, 871, 1957). The analysis was carried out on
tissue samples maintained under normal perfusion for a period of 90
min and after a period of hypoxia also lasting 90 min.
These tests showed that the ATP concentrations were substantially
diminished both in control animals and in the animals treated with
either carnitine alone or NADH alone. In the animals treated with the
combination of carnitine and NADH, on the othex hand, complete
protection against the ATP reduction induced by hypoxia was found.
These tests were therefore able to reveal the ability of the combination
of L-carnitine and NADH to protect the ATP present in papillary
muscle against a reduction induced by hypoxia to an extent which
could not be achieved either with L-carnitine alone or with NADH
alone, but which, surprisingly, can be achieved with the combination.
ATP concentration (mollg tissue)
Treatment Before hypoxia After hypoxia
Controls 1.54*0.31 0.40*0.051
Carnitine 100 mglkg 1.65*0.28 0,65*0.031
NADH 10 mglkg 1.60*0.30 0,65*0.044
Carnitine 100 mg/kg + NADH 10 mg/kg L90*0.37 1,5210.061
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_T_e_sts on the ability of L-carnitine and NADH to stimulate dopamine
production
These tests were performed on neuroblastoma cell cultures with a cell
concentration ranging from 15-30 to 60 million, incubated with 200 wg
of NADH/ml or with 2 mglmL of L-carnitine or with the two
components in combination.
The production of dopamine induced by NADH and L-carnitine was
assayed by HPLC according to the Mayer method (Mayer G.S., Strong
R.F., Currertt separation 4, 44, 1982) modified by Jonsson and Kelley
{Jonsson G., Holman H., Adams R.N., Central adrenaline neurones.
Ed. De Fuxe-Pergamon Press, 59, 1980; Kelley R., Oke A., Mefford L,
Life Sciences, 19, 995, 1976). The results of these tests demonstrate
that addition of NADH to the cell culture effectively induces an
increase in dopamine production related to the number of cells present.
A significantly greater increase is obtainable, however, when L-
carnitine, which alone produces only a very slight effect, is added to the
NADH solution: The synergistic effect is therefore marked in these
tests, too.
Percentage increase in dopamine synthesis in neuroblastoma cell cultures
incubated with
NADH or with carnitine as a function of the number of cells incubated
(millions)
N. cells % N. cells % N. cells
Treatment (millions) increase (millions} increase (millions) increase
NADH 100 pg/mL15 4.5 30 31,5 60 45.5
NADH 200 pg/mL15 11.8 30 40,6 60 65.6
Cainitine 1 15 --- 30 2,1 60 5.6
mg/mL
Carnitine 2 I5 30 3,3 60 6.6
mg/mL
NADH 100 wg/mL
+
Carnitine 1 15 6.6 30 45,2 60 50.6
mg/mL
NADH 200 ug/mL
+
Carnitine 2 15 18.4 30 56,4 60 70.5
mglmL
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MPTP (1-methyl-4-phenyl-1 2 3 6 tetrahydropvridine) test
The use of MPTP as a neurotoxin mainly active at the level of the
neuroskeletal system may be a significant experimental model for the
study of parkinsonism and its biochemical and clinical pathogenesis.
In both the monkey and the mouse, high doses of MPTP (40 mglkg)
induce the hypokinetic and bradykinetic symptoms typical of
Parkinson's disease accompanied by an appreciable reduction of dopa
and its metabolites. In these tests, it was studied whether the
behavioural and motility damage induced by MPTP in the mouse, as
well as the dopamine concentrations, could be modified and corrected
by the administration of NADH or L-carnitine alone or of both
substances in combination.
For these tests black mice of the C57 BE/6 strain with a body weight of
g were used; one group of these mice were kept as controls, while
the other groups were injected with two injections of 40 mglkg MPTP
subcutaneously with a 24 hr interval. Three weeks after the MPTP
injection the motility of all the treated animals and the control animals
was evaluated. The dopa assay was also carried out three weeks after
MPTP treatment. Treatment both with NADH and with carnitine was
given immediately prior to the start of the motility test; motility was
assessed using a plexiglas camera traversed at different heights by two
infrared rays according to the procedure described by Axcher (Archer
T., Fredrikson A., Psychophacrmacology, 88, 141, 1986).
The reduction in motility induced by MPTP proved greater than 80% in
the control mice, and motility was reduced by 60% and 70% by NADH
and L-carnitine alone, respectively, while with the combination of the
two substances motility was restored to practically normal levels (20%
reduction). Also of interest were the results for dopa concentrations in
striated muscle, which were reduced by 90% in control mice
administered MPTP, but presented almost normal levels in the treated
mice. In these tests, too, while the effect of L-carnitine alone appeared
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16
to be almost negligible and that of NADH was equal to 40°/, the
combination restored dopa to levels very close to the concentrations
normally present in this tissue.
Some examples of compositions according to the invention are reported
here below:
(I) L-carnitine inner salt mg 200
NADH mg 5
(2) L-carnitine inner salt mg 200
NADH mg 10
(3) Acetyl L-carnitine inner salt mg 250
NADH mg 5
(4) Acetyl L-carnitine inner salt mg 500
NADH mg 10
(5} Propionyl L-carnitine inner saltmg 250
NADH mg 5
{f) L-carnitine inner salt mg 200
NADH mg 5
Coenzyme Q10 mg 20
Pyridoxine mg 3
Selenium mg 20
Zinc mg 2
('l)L-carnitine inner salt mg 200 ,
NADH mg 5
Coenzyme Q 10 mg 20
Taurine mg 10
Inosine mg loo
Creatine mg 100
Piruvic acid mg x0
