melatonin clocking in presentation
TRANSCRIPT
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Melatonin Melatonin
Clocking in! in!
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Homeostasis
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Circadian rhythm
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Temperature
Growth hormone
Cortisone
Prolectine
Urinary K+
Chrono-biology
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Asthma 5am
Stroke 5-7amAllergic rhynitis 6am
Stable angina 10amunstable angina 1-3am
heart attack 6-8am
Hypertension 10am-2pm
Rheumatoid arthritis 6-8am
Osteoarthritis 4-6pm
Ulcer disease 4am5pmMigraine 4-6pm
Chrono-therapeutics
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Homeopathic Chrono Pharmacology
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Hamster Test
Biological
Suprachiasmatic nucleus
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Eye
SCN SCG
PinealSleep Wakecycle
Temperaturerhythm
Melatonin
Circadian rhythm physiology
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“Chronobiotics are substance which can therapeutically
adjust the timing of the circadian rhythms”
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2.00 P.M. 8.00 P.M. 3.00 A.M 7.00 A.M.
Time Of Day
Melatonin secretion
Melatonin secretion at night
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Melatonin and Sleep
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Normal circadian rhythm
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Winter circadian rhythm
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Summer circadian rhythm
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0 10 20 30 40 50 60 70
Sleep Duration
Melatonin Secretion
Age in Year
Melatonin levels sleep and age
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Melatonin Metabolism
Tryptophan 5Hydroxytryptophan 5Hydroxytryptamine
N Acetylserotonin
Melatonin
6-hydroxymelatonin SO4 (liver)
N-acetyl-5methoxy-kynurenamine
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Melatonin function?
• Regulate circadian rhythm
• Control other hormone through pituitary?
• Immunomodulator
• Oncostatic
• Free radical scavenger
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Disorders of melatonin
• Hypomelatonism
• Hypermelatonism
• Dysmelatonism
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Hypomelatonism
• Old age
• Pineal tumors
• Psychiatric disorders: depression, schizophrenia
• Mentally retarded and autistic
• Alcohlism
• Autonomopathy
• Klinefelder's and Turner's syndrome
• Neoplasm: liver, kidney, upper respiratory tract, breast, skin and prostate
• Some cases of coronary heart disease.
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Drug induced hypomelanonism
• Betablockers: Metaprolol->propranolol->Atenolol
• Alpha 2 blocker: Clonidine
• Naloxone• NSAID ibuprofen
• Alcohol, tobacco, caffeine
• Benzodiazepine
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Hypermelatonism
Seasonal affective disorder (SAD)
• Extreme fatigue and lack of energy• Increased need for sleep• Carbohydrate cravings• Weight gain• Reduced work productivity• Withdrawal from social contacts
• Exposure to light improve
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Dysmelatonism
Circadian rhythm SyndromeCircadian rhythm Syndrome
• Blind
• Jet lag
• Night shift workers ( Industrial jet lag)
• Delayed sleep phase syndrome
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Clinical features of CRS
• Disruption of sleep
• Decreased attention span– Decreased work
efficiency
– Work- and non-work related accidents
• Irritability• Headaches
• Fatigue
• Substance abuse
• Depression
• Reduced Immunity
• Cardiovascular and
• Gastrointestinal disorders
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Westward time zone flight
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Eastward time zone flight
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Delayed sleep phase syndrome
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Melatonin in insomnia
• Circadian rhythm disturbance most
effective
• Insomnia with psychological diseases
slight improvement
• Insomnia with structural disease no
response
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Advantage of melatonin
• Nontoxic
• No tolerance
• No hangover
• No suppression of REM sleep
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Administration
• 0.1mg to 200mg
• As little as 0.3 - 0.5 mg is usually effective as a sleep aid.
• Regular low dosage use for sleep should be limited to one month.
• Start slowly and increase till achieve normal sleep and no early morning drowsiness
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Pharmacokinetics
• Absorption: 60-150min
• Elimination half life: 45-60min
• Metabolism in liver and brain
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Melatonin in various age groups
• Age Group Teens - 20's: Should take Melatonin only occasionally for insomnia.
• Age Group 30 - 50: Can use it more frequently.
• Age Group over 60: Daily use is recommended.
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Caution• Psychotics
• Manic depression
• Immune system disorders: autoimmune and malignant disorders
• Diabetes and endocrine diseases
• Hypertension and cardiovascular disease
• Children and young reduces sperm count
• Pregnancy and breast feeding
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Adverse reaction(large dose)
• Morning drowsiness • Vivid dreams ->Nightmares, • Confusion • Nausea • Mild depression• Headache • Reduced sex drive• Vasoconstriction in Animal studies.
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Safety profile
• LD-50 not known
• Hypothermia
• There is little evidence to support
the safety of long-term use.
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Drug interaction
• Not well known
• Anti depressant may increase melatonin
level
• Estrogen reduces melatonin level and
• Melatonin reduces estrogen level
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Natural way to increase melatonin
• Early to bed and early to rise ………..
• Food: Oats, sweet corn, rice, barley, tomatoes and bananas
• Vitamin B3, B6 (dried apricots, barley, whole wheat, tuna and turkey, rice, bananas, lentils, shrimp and carrots)
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Natural way to increase Melatonin
• Meditate regularly
• Avoid too much caffeine and
alcohol, and stop smoking.
• Anti-oxidant supplements keeps
pineal gland healthy
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1.Extend life........…
2.Prevent pregnancy
3.Protect from free -
radical damage.…
4.Boost the immune
system.....…
5.Prevent cancer......
Melatonin Claims!
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Melatonin extend life
• Melatonin secretion reduces with aging in
80% population
• Cross transplantation of pineal gland
• Aging is due to oxidative injury to cell wall
and DNA
• Melatonin is a strong antioxidant
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Melatonin and Reproduction
• Melatonin controls growth hormone level
• Precocious puberty have low melatonin while delayed puberty have high
• Higher levels of melatonin are associated with male infertility and with the cessation of menstruation in women who exercise heavily or suffer badly from stress
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Immunomodulation
• Melatonin activated monocytes... and enhance
their ability to destroy nonself cells.
• Melatonin influenced the release of IL-1 proteins
that control aspects of blood-cell production and
the immune response.
• Melatonin could restore the function of T-helper
cells and IL2 in immunocompromised mice.
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Melatonin as antioxidant
• In vitro melatonin is more effective than glutathione in scavenging the highly toxic (OH) radical
• More efficient than vitamin E in neutralizing the peroxyl radical.
• It also stimulates the main antioxidant enzyme of the brain, glutathione peroxidase.
• In vivo melatonin is a potent antioxidant
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Melatonin in Cataract
•Glutathione depletion by Glutathione
synthesis inhibitor buthione sulfoxemine
(BSO) produces cataract in young mice
•Melatonin administration prevent cataract
formation by antioxidant effect
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Melatonin in Cancer
• Increased incidence of ovarian and breast cancer after pinealectomy
• Melatonin suppresses growth of prostate and breast carcinoma
• Anti cancer effect may be due to anti Prolectine, estrogen and growth hormone effect
• Melatonin changes expression of cell membrane estrogen receptor
• Melatonin may enhances anti tumor activity of IL2 by inhibiting tumor growth factor production in endometrial carcinoma
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More melatonin relationship
• Fibromyalgia: reduced melatonin • Epilepsy: high dose may be effective• Trypanosomiasis: Circadian rhythm
disturbance• Pain: to induce painless sleep• Tinnitus: to induce sleep• Hypercholesteremia: reduces LDL receptor• Antistress
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This billion year old
chronobiotic molecule
will change our approach
to medicine for the next
millenium
Thank you