pharmacology

1. Transcript
• 1. ENDORPHIN : A NATURAL ANALGESIC AND PLEASANT HORMONE BY: NEHA
JAIN M.Phil.Bioscience
• 2. 2 Endorphins "endogenous morphine" Beta-endorphin the best in pain relief Endorphins
production is hereditary, and due to this, its production level varies from one person to
another. High concentrations of endorphins in the brain produce a sense of euphoria,
enhance pleasure, and suppress pain, both emotionally and physically. Low concentrations
of endorphins in the brain people feel anxious and they are also more aware of pain.
• 3. OVERVIEW OF PRESENTATION 1) History 2) What is Endorphin 3) Types of
Endorphin 4) Control of Secretion 5) Transport and distribution 6) Receptors of endorphin
7) Binding: endorphin and receptor 8) Function as analgesic 9) Mode of action 10)Can we
get endorphin ? 11)Abnormalities of endorphin receptors 12)Receptors used by exogenous
opioid (morphine) 13)what is drug addiction ? 14)Can Methadone Fix to endorphin
Receptors? 15)Future of endorphin’s and other’s receptors
• 4. HISTORY  In 1970’s that many research allowed us to understand how the exogenous
opioid drugs work by studying the “endogenous opioid system”.  In 1973, H. Solomon
Snyder and Johns hopkins discovered the “endogenous opioid system”. Researchers also
determined the existence of opiate binding sites in the brain through the use of radioligand
binding assays.  In 1974, Rabi Simantov and Solomon H. Snyder isolated endogenous
opioid from the brain of a calf , and term is given "endorphin" (i.e. Endogenous morphine). 
In 1975, an endogenous opiate-like factor called enkephalin was found and shortly after this
two more classes of endogenous opiate peptides were isolated, the dynophorins and the
“endorphins”.
• 5. WHAT IS ENDORPHIN? A peptide hormone named Endorphin produced in the brain and
anterior pituitary. Endorphin inhibits pain perception. It is popularly called Body’s natural
analgesic or opiate. Endorphin is produced at the time of physical or emotional stress, such
as labor of child birth. Endorphin binds to the same receptors that binds exogenous opiates.
“Endorphin Affect Your Mood And Emotions And May Be Responsible For Your Body
Feeling Pleasure Even Euphoria For Your Body Feeling Pleasure”
• 6. alpha (α) endorphin - beta (β) endorphin Most powerful gamma (γ) endorphin - sigma (σ)
endorphin - TYPES OF ENDORPHIN Human body produces at least 20 different
endorphins ( benefits and uses are investigating) Special types are as follows: (made all by
16 to 31 amino acids )
• 7. β -ENDORPHIN • β -Endorphin is peptide hormones (consist of chains of amino acids)
----NH2 / NH3 + COOH • β -Endorphin is a 31 amino acid polypeptide • SEQUENCE: Ac -
Tyr - Gly - Gly - Phe - Met - Thr - Ser - Glu - Lys - Ser - Gln - Thr - Pro - Leu - Val - Thr -
Leu - Phe - Lys - Asn - Ala - Ile - Ile - Lys - Asn - Ala – His - Lys - Lys - Gly - Gln – OH • β-
endorphin is released by pituitary (into blood ) and hypothalamus ( into the spinal cord and
brain ) • β-endorphin is a cleavage product of pro- opiomelanocortin (POMC)
• 8. Hypothalamus Corticotropin releasing factor (CRF) Anterior Pituitary Pro-
Opiomelanocortin (POMC) Endorphin Hormone (EP) Central Nervous System
Environmental Cue “Stressor” ( pain) •Step 1: Cue perceived by CNS •Step 2: Signal sent to
hypothalamus (in brain) •Step 3: Hypothalamus secretes CRF (peptide), travels to pituitary
•Step 4: CRF causes protein pro-Opiomelanocortin hormone (POMC) to be cleaved, releases
Beta lipotropin •Step 5: lipotropin gets convert into Endorphin. •Step 6: Endorphin binds to
the nerve fiber. Brain Beta-lipotropin
• 9. ENDORPHIN HORMONE : AS CLEAVAGE PRODUCT pro-opiomelanocortin
polypeptide (POMC) ACTH b-lipotropin g-MSH g-lipotropina-MSH CLIP b-endorphin b-
MSH MET-enk
• 10. RECEPTORS OF ENDORPHIN • All of the endorphins bind to the opioid receptors in

2. the brain. • These analgesia- producing receptors are located in your brain, spinal cord, and
other nerve endings. Mu ( ) Receptor Analgesic (most important ) Delta( ) Receptor
Analgesic (predominantly ) Kappa () Receptor Analgesic (hyper- analgesic )
• 11. TRANSPORT AND DISTRIBUTION  β-endorphin is released by : 1. Pituitary (into
blood ) and 2. Hypothalamus ( into the spinal cord and brain )  Beta endorphin containing
nerve fibres spread widely from neurones in the hypothalamus, to make inhibitory contacts
with target neurones to reduce pain. Free hormones are rapidly eliminated from circulation
through kidney or liver. Hypothalamus
• 12. An Easy Way to Think of Receptors and Endorphins binding • Is to think of the
substance as a key and the receptor as a lock. • When the substance binds to the receptor it
opens the lock. • This in turn sends another signal or causes the release of a substance. •
When a lot of signals are sent a function happens like the release of a hormone.
• 13. BINDING OF ENDORPHIN & RECEPTOR  Portion of molecule Where ligand binds
Is called binding site.  If the molecule Is a receptor (like in a cell membrane) the binding
site is called receptor site.  The purpose of binding to target tissue is to elicit a response by
the target cell.
• 14. FUNCTION AS ANALGESIC Pain impulse feel Pain impulse stop
• 15. Before endorphin release After endorphin release FUNCTION AS ANALGESIC PAIN
IMPULSE STOP BY ENDORPHIN : MECHANISM hypothalamus
• 16. FUNCTION AS ANALGESIC PAIN IMPULSE STOP : BY ENDORPHIN
• 17. MODE OF ACTION The mu receptor is the strongest binding site of the body’s natural
pain killer, the class of opioid peptides called the endorphin. The mu receptor is a G-protein
linked receptor. When endorphin binds to the delta receptor is induces a conformational
change that causes the activation of a specific G-protein. This G-protein inhibits the
membrane bound enzyme adenylate cyclase and prevents the synthesis of cAMP.  The
transmission of the pain signal requires cAMP to act as a secondary messenger, and so
inhibition of this enzyme blocks the signal . (Pain-relieving effect by blocking the release of
substance P) Adenylcyclase Endorphin ATP cAMP AMP
• 18. 18 Calcium channels closed Potassium channels open K+ AC Gi [cAMP] Calciumentry
blocked [Ca2+] Decreased release of neurotransmitters Endorphin Receptor 2. Directaction
on K channels (alpha & beta subunit) Net effects: K+ conductance hyperpolarize neurons
Ca+ conductance neurotransmitter release 1. Couple to Gi & Go protein (neuronal
excitability) Pain reduced MODE OF ACTION
• 19. CAN WE GET ENDORPHIN ? Yes we can get : BY Chili Runner’s high Exercise
Music Laughing Meditation Acupuncture
• 20. ABNORMALITIES OF ENDORPHIN RECEPTORS However with some people :
When the lock (receptor) is damaged. No matter how much Endorphins may be near the
receptor because it does not function right the lock can not be opened. By Genetics/Birth
Defect A person can be born with defective receptors. This can make an individual more
susceptible to addiction By Exogenous drug And using opiates - not for pain - but when the
brain is flooded over and over again – the receptors stop working normally.
• 21. ENDORPHIN RECEPTORS USED BY EXOGENOUS OPIOID (Morphine) Morphine
Carbon Hydrogen Nitrogen Sulfur Oxygen Natural endorphin (a) Structures of endorphin
and morphine. Natural endorphin Endorphin receptors Morphine Brain cell (b) Binding to
endorphin receptors
• 22. ENDORPHIN MORPHINE Endogenous opioid. Exogenous opioid Powerful analgesic
18 to 500 times than morphine (Β-endorphin is 80 times) Less analgesic than endorphin
similar Molecular structure & Different chemical properties. It also Non-addictive Addictive
Does not cause addiction Side-effects : euphoria/ dysphoria, constipation, respiratory
depression, nausea/ vomiting etc. Receptors are : mu, kappa, delta Receptors are : mu,
kappa, sigma Metabolized quickly Metabolized slowly HOW DOES POTENCY DIFFER?

3. • 23. WHAT IS DRUG ADDICTION ? In the normal course Opiate Receptors and
Endorphins are kept in balance with one another. When the brain is flooded with exogenous
opiates, (heroin a morphine derivative) it mimic of endorphins so system gets confused. It
thinks it is making too many endorphins and shuts that down, But it still has all this excess
(heroin) and thinks that it also needs to make more receptors. Heroin addiction
• 24. What Happens Next…. • As more Opiate Receptors are made you need more heroin to
get the same effect so you use more. • And more receptors are made to accommodate the
extra what the brain thinks is endorphins. • For decreasing this effect- You need more
substance to get the same effect.
• 25. Can Methadone Fix to endorphin Receptors? • Methadone does normalize the damage
caused by drug use(heroin). • Synthetic. Long half-life Used to reduce withdrawal symptoms
of heroin addicts • And there is some evidence that for persons who have not used drugs
very long that methadone will stop the damage they are doing and over time can normalize
the system. • But this is a small minority – 30%. 72-84 hr (Slow excretion) Half-life > 24 hr
Half-life > 12 hr Methadone Heroin 2 hr ( fast excretion)
• 26. FUTURE OF ENDORPHIN’S AND OTHER’S RECEPTORS • The future of Opioid
Analgesics seems to be linked to the study of the Kappa Receptor. The kappa receptor
induces analgesia without the dangerous and unwanted side effects that the mu and delta
receptors are associated with. • However there are not any selectively strong agonists to this
receptor as of now. • Another area of research important to the future of opioid analgesics is
the study of the endogenous opioid peptides.
• 27. FUTURE OF ENDORPHIN’S AND OTHER’S RECEPTORS • Because these peptides
are endogenous, on metabolic degradation (unlike opiates) they break down to amino acids.
Hence, the metabolites are nontoxic and to not cause kidney and liver damage • Also,
because they are made from amino acid residues, a large number of analogs can be
synthesized from a few basic building blocks and simple modifications may be attempted to
develop analogs with a desired biological effect .
• 28. SUMMARY • Endorphin is best analgesic endogenous opioid. • For future research
endorphin receptors are very important.