.
CHEMICAL IDENTIFICATION
1H NMR assignment
1H NMR assignment
The chemical shifts and coupling constants of melatonin using CDCl3
as the standard are shown in Table 1 below;
IR Spectrum
The melatonin assay in this case is based upon selected ion monitoring
of the m/e 232 and /or 245 ions from trimethylsilyl (TMS) derivatives. An internal standard is simply an analoque of melatonin having a considerably
longer retention time, with intensed ions at m/e 232 and m/e 245. These
ions, which have exactly the same structure as those arising from melatonin,
can be used as standards for high resolution measurements on melatonin
as well as other methoxy indoles. This type of standard is preferred to
deuterium labeled analoques because of problems with deuterium exchange,
and difficulty in preparing such compounds with high isotopic purity.
: Partial mass
spectrum of the TMS melatonin (b) and its derivatives (a) and (c).
SYNTHESIS
The methods for the chemical synthesis of melatonin are generally not so
complicated and do not involve more than three steps of conversion. Three
synthesis reactions of melatonin from primary literatures are shown below;
Reaction 1
In 1958 melatonin was first isolated and characterised by A.B.Lerner. It
was know as one of a substituted 5-hydroxyindole derivative in the pineal
gland that could lighten pigment cells. It had not been know to exist in
biological tissue although it had been isolated as a urinary excretion
product in rats after administration of 5-hydroxytryptamine.
Melatonin or N-acetyl-5-methoxytryptamine (40 mg) was prepared by reducing 100 mg of 5-methoxyindole-3-acetonitrile with 160 mg of sodium and 2 ml of ethanol. Then the product was acetylated with 4 ml of both glacial acetic acid and acetic anhydride at 100 oC for 1 minute. Purification was achieved by countercerrent distribution and silicic acid chromatography.
.
Melatonin or N-acetyl-5-methoxytryptamine (40 mg) was prepared by reducing 100 mg of 5-methoxyindole-3-acetonitrile with 160 mg of sodium and 2 ml of ethanol. Then the product was acetylated with 4 ml of both glacial acetic acid and acetic anhydride at 100 oC for 1 minute. Purification was achieved by countercerrent distribution and silicic acid chromatography.
Reaction 2
5-Methoxytryptamine hydrochloride (1g, 4.75 mmole) was dissolved
in pyridine (10 ml) and acetic anhydride (10 ml) and kept overnight at
20 oC. The solution was poured onto iced, neutralised with dilute
hydrochloric acid and extracted with chloroform (2x25 ml). The combined
extracts were washed with water, dried in MgSO4 and evaporated
to afford a liquid of N,N diacetyltryptamine derivative. The liquid was
then poured into water (50 ml) and extracted with chlroform (2x25 ml).
The combined organic layers were washed with water (25 ml), dried in MgSO4
and evaporated to dryness. The residual solid crystallised from benzene
to afford melatonin 819 mg, 80% yield.
Reaction 3
The more reactive indoles (1a-1d)
were alkylated at the 3 position by reaction with nitroethene generated
in situ by thermolysis of nitroethyl acetate. The nitroethyl acetate used
for this purpose was prepared by acetylation of nitroethanol with acetic
anhydride using NaOAc as a catalyst. These conditions constitute a substantial
improvement of the overal yield of the reation. Reduction of the nitroethylated
indoles (2a-d) by hydrogenation over PtO2, followed by acetylation
fo the resluting tryptamines with acetic anhydride-pyridine completed the
synthesis of melatonin and its derivatives (4a-d).
The biosynthesis of melatonin (Fig.1) is initiated by the uptake of the
essential amino acid tryptophan into pineal parenchymal cells. Tryptophan
is the least abundant of essential amino acids in normal diets. It
is converted to another amino acid, 5-hydroxytryptophan, through the action
of the enzyme tryptopahn hydroxylase and then to 5-hydroxytryptamine (serotonin)
by the enzyme aromatic amino acid decarboxylase. Serotonin concentrations
are higher in the pineal than in any other organ or in any brain region.
They exhibit a striking diurnal rhythm remaining at a maximum level during
the daylight hours and falling by more than 80% soon after the onset of
darkness as the serotonin is converted to melatonin, 5-hydroxytryptophol
and other methoxyindoles. Serotonin's conversion to melatonin involves
two enzymes that are characteristic of the pineal : SNAT (serotonin-N-acetyltransferase)
which converts the serotonin to N-acetylserotonin, and HIOMT (hydroxyindole-O-methyltrasferase)
which trasfers a methyl group from S-adenosylmethionine to the 5-hydroxyl
of the N-acetylserotonin. The activities of both enzymes rise soon after
the onset of darkness
because of the enhanced release of norepinephrine from sympathetic neurons
terminating on the pineal parenchymal cells.
Another portion of the serotonin liberated from pineal cells after the onset of darkness is deaminated by the enzyme monoamine oxidase (MAO) and then either oxidized to form 5-hydroxyindole acetic acid or reduced to form 5-hydroxytryptophol (Fig.1). Both of these compounds are also substrates for HIOMT and can thus be converted in the pineal to 5-methoxyindole acetic acid 5-methoxytryptophol (Fig.1). The level of this latter indole, like that of melatonin, rises markedly in the pineal with the onset of darkness. Since 5-methoxytryptophol synthesis does not require the acetylation of serotonin, the nocturnal increase in pineal SNAT activity cannot be the trigger that causes pineal methoxyindole levels to rise. More likely, a single unexplained process- the intraparenchymal release of stored pineal serotonin, which then becomes accessible to both SNAT and MAO. This process ultimately controls the rates at which all three major pineal methoxyindoles are synthesized and generates the nocturnal increases in pineal melatonin and 5-methoxytryptophol. The proportion of available serotonin acetylated at any particular time of day or night depends on the relative activities of pineal SNAT and MAO at that time. The rates of methylation of all three 5-hydroxyindoles formed from pinela serotonin depends on HIOMT activity.
because of the enhanced release of norepinephrine from sympathetic neurons
terminating on the pineal parenchymal cells.
Another portion of the serotonin liberated from pineal cells after the onset of darkness is deaminated by the enzyme monoamine oxidase (MAO) and then either oxidized to form 5-hydroxyindole acetic acid or reduced to form 5-hydroxytryptophol (Fig.1). Both of these compounds are also substrates for HIOMT and can thus be converted in the pineal to 5-methoxyindole acetic acid 5-methoxytryptophol (Fig.1). The level of this latter indole, like that of melatonin, rises markedly in the pineal with the onset of darkness. Since 5-methoxytryptophol synthesis does not require the acetylation of serotonin, the nocturnal increase in pineal SNAT activity cannot be the trigger that causes pineal methoxyindole levels to rise. More likely, a single unexplained process- the intraparenchymal release of stored pineal serotonin, which then becomes accessible to both SNAT and MAO. This process ultimately controls the rates at which all three major pineal methoxyindoles are synthesized and generates the nocturnal increases in pineal melatonin and 5-methoxytryptophol. The proportion of available serotonin acetylated at any particular time of day or night depends on the relative activities of pineal SNAT and MAO at that time. The rates of methylation of all three 5-hydroxyindoles formed from pinela serotonin depends on HIOMT activity.
Fig.1 Biosynthesis of pineal methoxyindoles from serotonin
Serotonin may be either acetylated to form N-acetylserotonin through the action of the enzyme serotonin-N-acetyltransferase (SNAT), or oxidatively deaminated by monoamine oxidase (MAO) to yield an unstable aldehyde. This compound is then either oxidized to 5-hydroxyindole acetic acid by the enzyme aldehyde dehydrogenase (ADH), or reduced to from 5-hydroxytryptophol by aldehyde reductase (AR). Each of these 5-hydroxyindole derivatives of serotonin is a substrate for hydroxyindole-O-methyltrasferase (HIMOT). The enzymatic trasfer of a methyl group from S-adenosylmethionine to these hydroxyindoles yields melatonin (5-hydroxy-N-acetyltryptamine), 5-methoxyindole acetic acid and 5-methoxytryptophol respectively. Pineal serotonin is synthesized from the essential amino acid tryptophan by 5-hydroxylation folloed by decarboxylation. The first step in ths enzymic sequence is catalysed by tryptophan hydroxylase. The second step is catalysed by aromatic L-amino acid decarboxylase.
CHEMICAL REACTIONS
Reactions of melatonin and other 1-hydroxyindole derivatives
SCHEME 1
Click on image for enlarged version
Melatonin (2) was used to prepared 1-hydroxy indole derivative as shown in the scheme 1 above. Yield of melatonin was raised by up to 80% by reacting it with BF3-MeOH complex in reflusing MeOH. Then it was reduced to 2,3-dihydroindole (3a) with triethylsilane (Et3SiH) and trifluoroacetic acid (TFA) in 86% yield. Subsequence oxidation of (3a) with sodium tungstate dihydrate (Na2WO4.2H2O) afforded the desired 1-hydroxymelatonin (4a) in 28% yield.While bromination of 2,3-dihydro-N-methoxycarbonyltryptamine (5) with bromine in acetic acid generated monobromo (3b) and dibromo (3c) compounds in 61% and 30% yields respectively. Oxidation of (3b) and (3c) with Na2WO4.2H2O and 30% H2O2 produced the corresponding 1-hydroxytryptamines (4b) and (4c) in 57% and 51% yields . For the preparation of 1,4-dihydroxy-5-nitroindole (13), 4-hydroxy -5-nitroindole (11) was required as a starting material. It was also possible to form (11) by oxidation of 5-aminoindole (6) with m-chloroperbenzoic acid (mCPBA) in acetone. However, the yield was miserable (4%). In order to incrase the yield, an alternative synthesis method was developed. First, the reaction for obtaining 4-hydroxyindole-3-carboxaldehyde (8) from indole carboxaldehyde (7). The yield is now incrased to 70% with good reproducibility employing thallation with thallium tris(tris-fluoroacetate) and subsequenct treatment of the resultant thallium compound with cupric sulfate pentahydrate (2 mol eq.) in N,N-dimethylformamide and H2O at 120-130 oC. Nitration of (8) with cupric nitrate and acetic anhydride produced 5-nitro (9a) and 7-nitro (9b) compounds in 45% and 46% yields respectively. Since,direct conversion of (9a) to (11) was unsuccessful, (9a) was transformed to diacetyl compound (10) in 82% yield by treatment with refluxing acetic anhydride. Oxidation of 3-formyl group of (10 ) to carboxyl group with sodium chloride and subsequent treatment with 1N aqeuous sodium hydroxide caused hydrolysis and simultaneous decarboxylation to afford (11) in 90% yield. The reduction of (11) with Et3SiH and TFA afforded (12) in 91% yield. Subsequent oxidation of (12) with mCPBA (3 mol eq.) afforded the desired (13) in 66% yield, whereas with Na2WO4.2H2O and 30% H2O2 only 14% yield of (13) was produced.
1-hydroxy-3-methlsulfinylmethylindole (16a) was prepared as followed. 3-Methylthiomethylindole (14) was first prepared in 80% yield by reacting gramine with sodium methyl sulfide. Reduction of (14) with sodium cyanoborohydride (NaBH3CN) in AcOH successfully generated 2,3-dihydroindole (15) in 55% yield. Subsequent oxidation of (15) with Na2WO4.2H2O and 30% H2O2 produced (16a) in 27% yield. Formation of unstable 1-hydroxy-3-methylsulfonylmethylindole (16b) is confirmed as a 1-methoxy derivative but its isolation was not successful.
5-Acetyl-1,3,4,5-tetrahydropyrrolo[4,3,2-de]quinoline (18) is a readily available from 4-nitroindole-3-acetonitrile (17). (18) was reduced with NaBH3CN in AcOH and TFA to afford 90% yield of 2,3-dihydroindole (19). Oxidation of (19) with Na2WO4.2H2O and 30% H2O2 produced the desired 5-acetyl-1,3,4,5-tetrahydro-1-hydroxypyrrolo[4,3,2-de]quinoline (20) in 69% yield.
Reactions of melatonin and other 1-hydroxyindole derivatives
SCHEME 1
Click on image for enlarged version
Melatonin (2) was used to prepared 1-hydroxy indole derivative as shown in the scheme 1 above. Yield of melatonin was raised by up to 80% by reacting it with BF3-MeOH complex in reflusing MeOH. Then it was reduced to 2,3-dihydroindole (3a) with triethylsilane (Et3SiH) and trifluoroacetic acid (TFA) in 86% yield. Subsequence oxidation of (3a) with sodium tungstate dihydrate (Na2WO4.2H2O) afforded the desired 1-hydroxymelatonin (4a) in 28% yield.While bromination of 2,3-dihydro-N-methoxycarbonyltryptamine (5) with bromine in acetic acid generated monobromo (3b) and dibromo (3c) compounds in 61% and 30% yields respectively. Oxidation of (3b) and (3c) with Na2WO4.2H2O and 30% H2O2 produced the corresponding 1-hydroxytryptamines (4b) and (4c) in 57% and 51% yields . For the preparation of 1,4-dihydroxy-5-nitroindole (13), 4-hydroxy -5-nitroindole (11) was required as a starting material. It was also possible to form (11) by oxidation of 5-aminoindole (6) with m-chloroperbenzoic acid (mCPBA) in acetone. However, the yield was miserable (4%). In order to incrase the yield, an alternative synthesis method was developed. First, the reaction for obtaining 4-hydroxyindole-3-carboxaldehyde (8) from indole carboxaldehyde (7). The yield is now incrased to 70% with good reproducibility employing thallation with thallium tris(tris-fluoroacetate) and subsequenct treatment of the resultant thallium compound with cupric sulfate pentahydrate (2 mol eq.) in N,N-dimethylformamide and H2O at 120-130 oC. Nitration of (8) with cupric nitrate and acetic anhydride produced 5-nitro (9a) and 7-nitro (9b) compounds in 45% and 46% yields respectively. Since,direct conversion of (9a) to (11) was unsuccessful, (9a) was transformed to diacetyl compound (10) in 82% yield by treatment with refluxing acetic anhydride. Oxidation of 3-formyl group of (10 ) to carboxyl group with sodium chloride and subsequent treatment with 1N aqeuous sodium hydroxide caused hydrolysis and simultaneous decarboxylation to afford (11) in 90% yield. The reduction of (11) with Et3SiH and TFA afforded (12) in 91% yield. Subsequent oxidation of (12) with mCPBA (3 mol eq.) afforded the desired (13) in 66% yield, whereas with Na2WO4.2H2O and 30% H2O2 only 14% yield of (13) was produced.
1-hydroxy-3-methlsulfinylmethylindole (16a) was prepared as followed. 3-Methylthiomethylindole (14) was first prepared in 80% yield by reacting gramine with sodium methyl sulfide. Reduction of (14) with sodium cyanoborohydride (NaBH3CN) in AcOH successfully generated 2,3-dihydroindole (15) in 55% yield. Subsequent oxidation of (15) with Na2WO4.2H2O and 30% H2O2 produced (16a) in 27% yield. Formation of unstable 1-hydroxy-3-methylsulfonylmethylindole (16b) is confirmed as a 1-methoxy derivative but its isolation was not successful.
5-Acetyl-1,3,4,5-tetrahydropyrrolo[4,3,2-de]quinoline (18) is a readily available from 4-nitroindole-3-acetonitrile (17). (18) was reduced with NaBH3CN in AcOH and TFA to afford 90% yield of 2,3-dihydroindole (19). Oxidation of (19) with Na2WO4.2H2O and 30% H2O2 produced the desired 5-acetyl-1,3,4,5-tetrahydro-1-hydroxypyrrolo[4,3,2-de]quinoline (20) in 69% yield.
STRUCTURE
OF MELATONIN
picture of melatonin (2D) with labelled atoms
The molecular structure and configuration of melatonin (N-acetyl- 5 - methoxy tryptamine) can be determined by X-ray diffraction method. It is crystallized from benzene solution as yellow plates (m.p. 118-119 oC ), which are shown to be monoxlinic with unit cell parameters of a= 7.711, b=9.282, c=17.107 Ao and ß =96.77 o from systematic extinctions. The density value of 1.269 g/cc measured by the flotation method in calsium chloride aqueous solution, indicates that there are four molecules in a unit cell.
The main C-C distance in the benzene ring is 1.402 Ao, while those of C-C and C-N distances in the pyrrole ring are 1.405 Ao and 1.394 Ao respectively. The indole part of melatonin is planar, the average deviation of the atoms from the plane is 0.011 Ao and the maximum deviation is 0.022 Ao for N(2). C(1), C(2) and O(1) of acetyl groul and N(1) are almost strictly in a plane. This plane forms a dihedral angle of 12 o with that of the indole ring. The atomic parameters and temperature factors (Bij) for heavy atoms are listed in Table 1 below;
Table 1 : The atomic parameters and temperature factors (Bij) for heavy atoms in melatonin molecule
picture of melatonin (2D) with labelled atoms
The molecular structure and configuration of melatonin (N-acetyl- 5 - methoxy tryptamine) can be determined by X-ray diffraction method. It is crystallized from benzene solution as yellow plates (m.p. 118-119 oC ), which are shown to be monoxlinic with unit cell parameters of a= 7.711, b=9.282, c=17.107 Ao and ß =96.77 o from systematic extinctions. The density value of 1.269 g/cc measured by the flotation method in calsium chloride aqueous solution, indicates that there are four molecules in a unit cell.
The main C-C distance in the benzene ring is 1.402 Ao, while those of C-C and C-N distances in the pyrrole ring are 1.405 Ao and 1.394 Ao respectively. The indole part of melatonin is planar, the average deviation of the atoms from the plane is 0.011 Ao and the maximum deviation is 0.022 Ao for N(2). C(1), C(2) and O(1) of acetyl groul and N(1) are almost strictly in a plane. This plane forms a dihedral angle of 12 o with that of the indole ring. The atomic parameters and temperature factors (Bij) for heavy atoms are listed in Table 1 below;
Table 1 : The atomic parameters and temperature factors (Bij) for heavy atoms in melatonin molecule
- Bij are temperature factors ( x 104)
- Anisotropic temperature factors are in the form : T= exp[-(B11h2 + B22K2 + B33l2 + B12hk + B13hl +B23kl)].
- The average standard deviations of the coordinations are about 0.007, 0.006 and 0.005 ao for carbon, nitrogen and oxygen atoms respectively
The torsion angle as defined by Klyne and Prelog (W.
Klyne and V; Prolog, Experientia, 16, 521 (1960) ) is +0.4o
(syn-periplanar) for the atoms C(13)-O(2)-C(10)-C(9), while the equivalent
angle in 5-methoxy-(N,N)-dimethyltryptamine hydrochloride is +2.5o .
Three important torsion angles C(2)-N(1)-C(3)-C(4), N(1)-C(3)-C(4)-C(5) and C(3)-C(4)-C(6) are +171o (anti-periplanar), -171o (anti-periplanar) and +6o (syn-periplanar) respectively. The extended configuration of the side chain attached to C(5) atom is also found in serotonin-creatinine sulphate complex.
The crystal structure of melatonin reviews that two melatonin molecules are hydrogen-bonded through N(2)-H----O(1) (2.87 Ao) into dimer related by centre of symmetry. These dimers are linked together by N(1)-H----O(1) hydrogen bonds (2.95 Ao ) in the directions of b and c-axes. The normal van der Waals contacts are found between adjacent indole rings or methoxy groups to stabilise the crystal structure.
.Three important torsion angles C(2)-N(1)-C(3)-C(4), N(1)-C(3)-C(4)-C(5) and C(3)-C(4)-C(6) are +171o (anti-periplanar), -171o (anti-periplanar) and +6o (syn-periplanar) respectively. The extended configuration of the side chain attached to C(5) atom is also found in serotonin-creatinine sulphate complex
.The crystal structure of melatonin reviews that two melatonin molecules are hydrogen-bonded through N(2)-H----O(1) (2.87 Ao) into dimer related by centre of symmetry. These dimers are linked together by N(1)-H----O(1) hydrogen bonds (2.95 Ao ) in the directions of b and c-axes. The normal van der Waals contacts are found between adjacent indole rings or methoxy groups to stabilise the crystal structure.
INTRODUCTION
structure of melatonin or ( N-Acetyl-5-methoxytryptamine)
structure of melatonin or ( N-Acetyl-5-methoxytryptamine)
Melatonin or 5-methoxy-N-acetyltryptamine is an important
hormone that plays a role in regurating the neuroendocrine system. It
plays an important role in the reguration of the circadian sleep-wake cycle.
It also controls essential functions such as metabolism, sex drive, reproduction,
appetite, balance, muscular coordination and immune system in fighting
off diseases triggered by bacteria, viruses, chemical pollutants and excessive
free radical activity. It is normally released during the night in response
to environmental changes in light levels by the peneal gland which is a
tiny gland burried deep in the brain behind the eyes of mammals. The pineal
itself is controlled by a paired cluster of nerve cells located just above
the optic chiasm in the hypothalamus. These cells are known as the suprachiasmatic
nuclei (SCN) and they contain the circadian pacemaker. Each night the SCN
send impulses, via a series of neurons in the hypothalamus and spinal cord,
up to the pineal gland to stimulate melatonin secretion. The timing mechanism
in the SCN itself is controlled by sunlight that enters the retina and
reaches the SCN via the retinohypothalamic pathway. The amount of melatonin
circulating in the blood has been shown to rise and fall during a day.
The 24-hour cycle of melatonin production in Human is shown in figure 1
below;
Figure 1: the amount of melatonin secretion from human pineal gland during various time of day
From the graph above it can be seen that melatonin levels reach the highest value during the middle of the night and decline to the lower amounts during daytime.
Since its structure was first discovered in 1958 by A.B. Lerner,
melatonin has been studied extensively. There are over 4,000 published
studied in the scientific literature about melatonin. Every week, five
to fifteen new studies are published, making melatonin one of the hottest
subjects of life extension research. In toxicity studies conducted on humans,
doses of melatonin ranging from 300 mg a day for nine months to 1000 mg
a day for six weeks porduced no toxicity or adverse reactions other than
daytime fatigue.
,
melatonin has been studied extensively. There are over 4,000 published
studied in the scientific literature about melatonin. Every week, five
to fifteen new studies are published, making melatonin one of the hottest
subjects of life extension research. In toxicity studies conducted on humans,
doses of melatonin ranging from 300 mg a day for nine months to 1000 mg
a day for six weeks porduced no toxicity or adverse reactions other than
daytime fatigue.
So what is so hot about melatonin ?
Melatonin is an effective
sleeping pill. Taking low dose of melatonin on a nightly basis at appropriate
sleep times allows the body to naturally adapt to altered day and night
patterns. Synthesis of melatonin in the human body declines with advancing
age and this is one of the reasons why elders have more sleep disorder
problems than children.
Research shows that the administration
of melatonin improves the sleep onset in blind subjects unable to
synchronize with the solar cycle.It
may also be an effective hypnotic for insominiacs or travellers who suffer
from jet lag. In 1994 Wurtman et al. at the Massachusetts Institute of
Technology reported the results of a sleep laboratory study involving 20
subjects with normal sleep habits. Subjects were administered melatonin
in low doses (1-10 mg) or placebo, and sleep was monitired in the lab during
five 8-hour test sessions. Compared with placebo, melatonin (all doses)
decreased the time it took to fall asleep and increased sleep duration.
Subjects who received melatonin 1 mg fell asleep in an average of 6 minutes
compared with 17 minutes for subjects who received placebo. The investigators
concluded that melatonin may be as effective a hypnotic as the benzodiazepines.
.It
may also be an effective hypnotic for insominiacs or travellers who suffer
from jet lag. In 1994 Wurtman et al. at the Massachusetts Institute of
Technology reported the results of a sleep laboratory study involving 20
subjects with normal sleep habits. Subjects were administered melatonin
in low doses (1-10 mg) or placebo, and sleep was monitired in the lab during
five 8-hour test sessions. Compared with placebo, melatonin (all doses)
decreased the time it took to fall asleep and increased sleep duration.
Subjects who received melatonin 1 mg fell asleep in an average of 6 minutes
compared with 17 minutes for subjects who received placebo. The investigators
concluded that melatonin may be as effective a hypnotic as the benzodiazepines.
Apart from its treat
with sleeping disorders, there is also a correlation between the low level
of melatonin and increase in risk of cancer. Research studies have demonstrated
that melatonin can prevent chemically induced mammary tumors in laboratory
rats and can also inhibit the proliferation of human breast cancer cells
in tissue culture. For more detail about role of melatonin concerning cancer
and tumer see melatonin immunity
and cancer in human.
Melatonin is available commercially
from several unregurated health-food suppliers. Soon after the publication
of the Wurtman report, health food stores began selling out of melatonin
and consumers flooded Wurtman's lab with requests for melatonin for insominia
or jet lag. The response to these requests has been to point out that melatonin
is not FDA approved. There is no labeling for dosage and side effects,
there are no controls for purity and self-medicating with an unregulated
product is a mistake.However, melatonin demand has not yet declined. In
1994, one manufacturer of melatonin in USA increased the amount
of melatonin sold the previous year by three-fold.
.
What to consider before using melatoninsupplement?
The first thing to consider is that sometimes, less is more. Although melatonin plays an extremely important role in our bodies, it is present only in tiny amounts, even when we are at our youthful peak. Melatonin capsules vary in dosage from less than 0.1 mg up to 6 mg. Although no severe side effects have been reported at dosages up to 10 mg daily, in some people it may cause morning drowsiness. Melatonin is not recommended for pregnent women nor should be intended to use by persons under 25 years of age. People who have serious illnesses such as autoimmune disorder, leukemia or lymphoma should consult a physician familear with melatonin before usage. Immune suppressing drugs such as cortisol and cyclosporine may react adversely with melatonin as may anti-depressants. People who are diabetic, experience major depression or have a hormonal imbalance should also take caution. Pregnent of nursing mather should avoid melatonin supplements. They are already transmitting melatonin to fetus or infant via the placenta or their milk. It is unknown if increasing their own melatonin levels might adversely affect the child.
Melatonin
Chemical names :
N-acetyl-5-methoxytrptamine
N-[2-(5-methoxy-1H-indol-3-yl)ethyl]
3-(N-Acetyl-2-aminoethyl)-5-methoxy indole
N-[2-(5-Methoxy-1H-indol-3-yl]
N-[2-(5-methoxy-1H-indol-3-yl)ethyl]
3-(N-Acetyl-2-aminoethyl)-5-methoxy indole
N-[2-(5-Methoxy-1H-indol-3-yl]
Empirical formula :
C13H16N2O2
Molecular mass :
232.28 amu
Melting point :
116~118 oC
Possible harzard :
No possible harzard has been reported
Normal state :
Crystalline solid
Density:
1.29 g/cc
Colour :
Pale yellow
Prices :
Laboratory analytical proposes
:
£ 29.10 (1 g)
£ 7.90 (100 mg)
£ 12.00 (250 mg)
£ 32.00 (1 g)
Melatonin tablet retail prices
:
£ 20.00 (100 x 300 mcg)
:
£ 29.10 (1 g)
£ 7.90 (100 mg)
£ 12.00 (250 mg)
£ 32.00 (1 g)
Melatonin tablet retail prices
:
£ 20.00 (100 x 300 mcg)
BNN
:
205542
:
205542
EC no.
:
2007977
:
2007977
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