Melatonin clocking in presentation
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Transcript of Melatonin clocking in presentation
Melatonin Melatonin
Clocking in! in!
Homeostasis
Circadian rhythm
Temperature
Growth hormone
Cortisone
Prolectine
Urinary K+
Chrono-biology
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
Homeopathic Chrono Pharmacology
Hamster Test
Biological
Suprachiasmatic nucleus
Eye
SCN SCG
PinealSleep Wakecycle
Temperaturerhythm
Melatonin
Circadian rhythm physiology
“Chronobiotics are substance which can therapeutically
adjust the timing of the circadian rhythms”
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
Melatonin and Sleep
Normal circadian rhythm
Winter circadian rhythm
Summer circadian rhythm
0 10 20 30 40 50 60 70
Sleep Duration
Melatonin Secretion
Age in Year
Melatonin levels sleep and age
Melatonin Metabolism
Tryptophan 5Hydroxytryptophan 5Hydroxytryptamine
N Acetylserotonin
Melatonin
6-hydroxymelatonin SO4 (liver)
N-acetyl-5methoxy-kynurenamine
Melatonin function?
• Regulate circadian rhythm
• Control other hormone through pituitary?
• Immunomodulator
• Oncostatic
• Free radical scavenger
Disorders of melatonin
• Hypomelatonism
• Hypermelatonism
• Dysmelatonism
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.
Drug induced hypomelanonism
• Betablockers: Metaprolol->propranolol->Atenolol
• Alpha 2 blocker: Clonidine
• Naloxone• NSAID ibuprofen
• Alcohol, tobacco, caffeine
• Benzodiazepine
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
Dysmelatonism
Circadian rhythm SyndromeCircadian rhythm Syndrome
• Blind
• Jet lag
• Night shift workers ( Industrial jet lag)
• Delayed sleep phase syndrome
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
Westward time zone flight
Eastward time zone flight
Delayed sleep phase syndrome
Melatonin in insomnia
• Circadian rhythm disturbance most
effective
• Insomnia with psychological diseases
slight improvement
• Insomnia with structural disease no
response
Advantage of melatonin
• Nontoxic
• No tolerance
• No hangover
• No suppression of REM sleep
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
Pharmacokinetics
• Absorption: 60-150min
• Elimination half life: 45-60min
• Metabolism in liver and brain
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.
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
Adverse reaction(large dose)
• Morning drowsiness • Vivid dreams ->Nightmares, • Confusion • Nausea • Mild depression• Headache • Reduced sex drive• Vasoconstriction in Animal studies.
Safety profile
• LD-50 not known
• Hypothermia
• There is little evidence to support
the safety of long-term use.
Drug interaction
• Not well known
• Anti depressant may increase melatonin
level
• Estrogen reduces melatonin level and
• Melatonin reduces estrogen level
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)
Natural way to increase Melatonin
• Meditate regularly
• Avoid too much caffeine and
alcohol, and stop smoking.
• Anti-oxidant supplements keeps
pineal gland healthy
1.Extend life........…
2.Prevent pregnancy
3.Protect from free -
radical damage.…
4.Boost the immune
system.....…
5.Prevent cancer......
Melatonin Claims!
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
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
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.
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
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
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
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
This billion year old
chronobiotic molecule
will change our approach
to medicine for the next
millenium
Thank you