Learn the nor adrenergic transmission in ANS. Synthesis, storage ,release, uptake,metabolism of nor-adrenaline. Types of adrenoceptors. Agonist and antagonist of adrenoceptors.
Neurohumoral transmission in CNS ,special emphasis on importance of various neurotransmitters like with GABA, Glutamate, Glycine, serotonin and dopamine
Neurohumoral transmission in CNS ,special emphasis on importance of various neurotransmitters like with GABA, Glutamate, Glycine, serotonin and dopamine
Neurotransmitters/General aspect and steps involved in neurotransmission.pptxSIRAJUDDIN MOLLA
Neurotransmission (Latin: transmission "passage, crossing" from transmitter "send, let through"), is the process by which signalling molecules called neurotransmitters are released by the axon terminal of a neuron and bind to and react with the receptors on the dendrites of another neuron
This presentation impart a knowledge about Histamine,receptor,and antagonist.
Recent advances also mentioned like H3 & H4 receptors role in cognitive impairment etc.
At the end of this e-learning session you are able to…
A. Discuss Neurohumoral Transmission.
B. Explain role of GABA, Glutamate, Glycine, Serotonin and Dopamine in neurohumoral transmission.
For 30+ video lecture series on Pharmacology Experiment as per PCI B Pharm Syllabus refer link given below: https://www.youtube.com/playlist?list=PLBVbJ9HCa1Ba6WSJjeBaK0HMF79hdad3g
For 2+ video lecture series on Pharmacoeconomics refer link given below: https://www.youtube.com/playlist?list=PLBVbJ9HCa1BY8U1TnlcHttsRB8hwpoJRL
For 5+ video lecture series on Pharmacoepidemiology refer link given below: https://www.youtube.com/playlist?list=PLBVbJ9HCa1BbqIaLoMmuF0Bf66SMFZtnb
For 5+ video lecture series on Drug discovery refer link given below: https://www.youtube.com/playlist?list=PLBVbJ9HCa1Bbn9IE6c4MagVHZMNNinJov
For 5+ video lecture series on Drugs used in Special population use link given below: https://www.youtube.com/playlist?list=PLBVbJ9HCa1BZAed7zkXxyrgomJx2sSwHR
For 5+ video lecture series on Adverse Drug Reaction use link given below: https://www.youtube.com/playlist?list=PLBVbJ9HCa1BbWpd06N6RcV2q0K3JT29Wv
For 2+ video lecture series on Therapeutic drug monitoring refer link given below: https://www.youtube.com/playlist?list=PLBVbJ9HCa1BZQtOerZuDjx4yo0eOeTHIy
For 26+ video lecture series on Drugs act on central nervous system refer link given below: https://www.youtube.com/playlist?list=PLBVbJ9HCa1BY9xHaplYCYG26ALtIQp5aC
For 6+ video lecture series on drugs act on Gastrointestinal tract refer link given below: https://www.youtube.com/playlist?list=PLBVbJ9HCa1BYgHRHwuarKTt96bu_2L5WK
To support this channel you can through UPI ID: abushaikh07-yahoo.com@okhdfcbank
For More Such Learning You Can Subscribe to My YouTube Channel: https://www.youtube.com/channel/UC5o-WkzmDJaF7udyAP2jtgw/featured?sub_confirmation=1
Facebook Page: https://www.facebook.com/asacademylearningforever
Website Blog: https://itasacademy.blogspot.com/
Seretonin (5HT) and Its Antagonists PharmacologyPranatiChavan
Serotonin is a chemical that has a wide variety of functions in the human body. It is sometimes called the happy chemical, because it contributes to wellbeing and happiness.
The scientific name for serotonin is 5-hydroxytryptamine, or 5-HT. It is mainly found in the brain, bowels, and blood platelets.
Serotonin is used to transmit messages between nerve cells, it is thought to be active in constricting smooth muscles, and it contributes to wellbeing and happiness, among other things. As the precursor for melatonin, it helps regulate the body’s sleep-wake cycles and the internal clock.
It is thought to play a role in appetite, the emotions, and motor, cognitive, and autonomic functions. However, it is not known exactly if serotonin affects these directly, or if it has an overall role in co-ordinating the nervous system.
In this slide contains diabetics, classification, symptoms, complication, invivo and invitro screening models of anti diabetics.
Presented by: GEETHANJALI ADAPALA (Department of pharmacology).
RIPER, anantapur
Classification of receptors family by vivek sharmaAnimatedWorld
Definition- Receptor are the biologic molecule to which drug bind and produces a measurable response.
So, enzyme and structural proteins can be considerd to be pharmacologic receptors.
Majorly receptor are of 4 types and the molecule or a drug interact to receptor to give response often called as ligand.
The type of receptor a ligand will bind is depend on the nature of ligand.
Hydrophilliic ligand binds to the receptor found on the cell surface.
Hydrophobic ligand can enter the cell membrane to intract the receptor present on inside the cells.
Classification of Receptors
A. Cell surface receptor
Ligand-gated Ion Channel
G Protein Coupled Receptor
Enzyme linked Receptor
B. Intracellular Receptor
Nuclear Receptor
Neurotransmitters/General aspect and steps involved in neurotransmission.pptxSIRAJUDDIN MOLLA
Neurotransmission (Latin: transmission "passage, crossing" from transmitter "send, let through"), is the process by which signalling molecules called neurotransmitters are released by the axon terminal of a neuron and bind to and react with the receptors on the dendrites of another neuron
This presentation impart a knowledge about Histamine,receptor,and antagonist.
Recent advances also mentioned like H3 & H4 receptors role in cognitive impairment etc.
At the end of this e-learning session you are able to…
A. Discuss Neurohumoral Transmission.
B. Explain role of GABA, Glutamate, Glycine, Serotonin and Dopamine in neurohumoral transmission.
For 30+ video lecture series on Pharmacology Experiment as per PCI B Pharm Syllabus refer link given below: https://www.youtube.com/playlist?list=PLBVbJ9HCa1Ba6WSJjeBaK0HMF79hdad3g
For 2+ video lecture series on Pharmacoeconomics refer link given below: https://www.youtube.com/playlist?list=PLBVbJ9HCa1BY8U1TnlcHttsRB8hwpoJRL
For 5+ video lecture series on Pharmacoepidemiology refer link given below: https://www.youtube.com/playlist?list=PLBVbJ9HCa1BbqIaLoMmuF0Bf66SMFZtnb
For 5+ video lecture series on Drug discovery refer link given below: https://www.youtube.com/playlist?list=PLBVbJ9HCa1Bbn9IE6c4MagVHZMNNinJov
For 5+ video lecture series on Drugs used in Special population use link given below: https://www.youtube.com/playlist?list=PLBVbJ9HCa1BZAed7zkXxyrgomJx2sSwHR
For 5+ video lecture series on Adverse Drug Reaction use link given below: https://www.youtube.com/playlist?list=PLBVbJ9HCa1BbWpd06N6RcV2q0K3JT29Wv
For 2+ video lecture series on Therapeutic drug monitoring refer link given below: https://www.youtube.com/playlist?list=PLBVbJ9HCa1BZQtOerZuDjx4yo0eOeTHIy
For 26+ video lecture series on Drugs act on central nervous system refer link given below: https://www.youtube.com/playlist?list=PLBVbJ9HCa1BY9xHaplYCYG26ALtIQp5aC
For 6+ video lecture series on drugs act on Gastrointestinal tract refer link given below: https://www.youtube.com/playlist?list=PLBVbJ9HCa1BYgHRHwuarKTt96bu_2L5WK
To support this channel you can through UPI ID: abushaikh07-yahoo.com@okhdfcbank
For More Such Learning You Can Subscribe to My YouTube Channel: https://www.youtube.com/channel/UC5o-WkzmDJaF7udyAP2jtgw/featured?sub_confirmation=1
Facebook Page: https://www.facebook.com/asacademylearningforever
Website Blog: https://itasacademy.blogspot.com/
Seretonin (5HT) and Its Antagonists PharmacologyPranatiChavan
Serotonin is a chemical that has a wide variety of functions in the human body. It is sometimes called the happy chemical, because it contributes to wellbeing and happiness.
The scientific name for serotonin is 5-hydroxytryptamine, or 5-HT. It is mainly found in the brain, bowels, and blood platelets.
Serotonin is used to transmit messages between nerve cells, it is thought to be active in constricting smooth muscles, and it contributes to wellbeing and happiness, among other things. As the precursor for melatonin, it helps regulate the body’s sleep-wake cycles and the internal clock.
It is thought to play a role in appetite, the emotions, and motor, cognitive, and autonomic functions. However, it is not known exactly if serotonin affects these directly, or if it has an overall role in co-ordinating the nervous system.
In this slide contains diabetics, classification, symptoms, complication, invivo and invitro screening models of anti diabetics.
Presented by: GEETHANJALI ADAPALA (Department of pharmacology).
RIPER, anantapur
Classification of receptors family by vivek sharmaAnimatedWorld
Definition- Receptor are the biologic molecule to which drug bind and produces a measurable response.
So, enzyme and structural proteins can be considerd to be pharmacologic receptors.
Majorly receptor are of 4 types and the molecule or a drug interact to receptor to give response often called as ligand.
The type of receptor a ligand will bind is depend on the nature of ligand.
Hydrophilliic ligand binds to the receptor found on the cell surface.
Hydrophobic ligand can enter the cell membrane to intract the receptor present on inside the cells.
Classification of Receptors
A. Cell surface receptor
Ligand-gated Ion Channel
G Protein Coupled Receptor
Enzyme linked Receptor
B. Intracellular Receptor
Nuclear Receptor
The all the content in this profile is completed by the teachers, students as well as other health care peoples.
thank you, all the respected peoples, for giving the information to complete this presentation.
this information is free to use by anyone.
Agonists at adrenergic receptors are either direct-acting or indirect-acting. Catecholamines, norepinephrine, and epinephrine are direct-acting and nonselective adrenergic agonists. Indirect-acting agonists cause the release of the neurotransmitter norepinephrine from sympathetic nerve terminal
Sympathomimetics or Adrenergic Agonists (Introduction, Classification, Adenor...Ahmad Naeem
Sympathomimetics or adrenergic agonists (introduction, classification, adenoreceptors, neurtransmission, direct acting, indirect acting, mixed action agonists, summary)
Drugs that partially or completely mimic the effects of transmitter substances of the sympathetic nervous system. On the basis of chemical structure we divide Sympathomimetics into
1. Catecholamine
2. Non-Catecholamine
Adrenergic drugs that activate adrenergic receptors are termed
as sympathomimetics, Some sympathomimetics directly activate
adrenergic receptors (direct-acting agonists), while others act
indirectly by enhancing release or blocking reuptake of norepinephrine (indirect-acting agonists). Adrenergic transmission is restricted to the sympathetic division of the ANS. There are three closely related endogenous catecholamine's (CAs).
1. Noradrenaline (NA): It acts as transmitter at postganglionic sympathetic sites (except sweat glands, hair follicles and some vasodilator fibers) and in certain areas of brain.
2. Adrenaline (Adr) It is secreted by adrenal medulla and may have a transmitter role in the brain.
3. Dopamine (DA) It is a major transmitter in basal ganglia, limbic system, CTZ, anterior pituitary, etc. and in a limited manner in the periphery
Mechanism of Action , Therapeutic uses and adverse effects of Adrenergic Agonists
1. Direct-acting agonists:
These drugs act directly on α or β receptors, producing effects similar to those that occur following stimulation of sympathetic nerves or release of epinephrine from the adrenal medulla.
Examples of direct-acting agonists include epinephrine,
norepinephrine, isoproterenol, and phenylephrine.
2. Indirect-acting agonists:
These agents may block the reuptake of norepinephrine or cause the release of norepinephrine from the cytoplasmic pools or vesicles of adrenergic neuron. The norepinephrine then traverses the synapse and binds to α or β receptors.
Examples of reuptake inhibitors and agents that cause norepinephrine release include cocaine and amphetamines,
respectively.
3. Mixed-action agonists:
Ephedrine and its stereoisomer, pseudoephedrine, both stimulate adrenoceptors directly and release norepinephrine
from the adrenergic neuron.
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
HOT NEW PRODUCT! BIG SALES FAST SHIPPING NOW FROM CHINA!! EU KU DB BK substit...GL Anaacs
Contact us if you are interested:
Email / Skype : kefaya1771@gmail.com
Threema: PXHY5PDH
New BATCH Ku !!! MUCH IN DEMAND FAST SALE EVERY BATCH HAPPY GOOD EFFECT BIG BATCH !
Contact me on Threema or skype to start big business!!
Hot-sale products:
NEW HOT EUTYLONE WHITE CRYSTAL!!
5cl-adba precursor (semi finished )
5cl-adba raw materials
ADBB precursor (semi finished )
ADBB raw materials
APVP powder
5fadb/4f-adb
Jwh018 / Jwh210
Eutylone crystal
Protonitazene (hydrochloride) CAS: 119276-01-6
Flubrotizolam CAS: 57801-95-3
Metonitazene CAS: 14680-51-4
Payment terms: Western Union,MoneyGram,Bitcoin or USDT.
Deliver Time: Usually 7-15days
Shipping method: FedEx, TNT, DHL,UPS etc.Our deliveries are 100% safe, fast, reliable and discreet.
Samples will be sent for your evaluation!If you are interested in, please contact me, let's talk details.
We specializes in exporting high quality Research chemical, medical intermediate, Pharmaceutical chemicals and so on. Products are exported to USA, Canada, France, Korea, Japan,Russia, Southeast Asia and other countries.
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
Basavarajeeyam is an important text for ayurvedic physician belonging to andhra pradehs. It is a popular compendium in various parts of our country as well as in andhra pradesh. The content of the text was presented in sanskrit and telugu language (Bilingual). One of the most famous book in ayurvedic pharmaceutics and therapeutics. This book contains 25 chapters called as prakaranas. Many rasaoushadis were explained, pioneer of dhatu druti, nadi pareeksha, mutra pareeksha etc. Belongs to the period of 15-16 century. New diseases like upadamsha, phiranga rogas are explained.
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
MANAGEMENT OF ATRIOVENTRICULAR CONDUCTION BLOCK.pdfJim Jacob Roy
Cardiac conduction defects can occur due to various causes.
Atrioventricular conduction blocks ( AV blocks ) are classified into 3 types.
This document describes the acute management of AV block.
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
2. The transmission of impulse
through synapse and neuro-effector
junction by the release of humoral
(chemical) substances…
What is neurohumoral transmission
3. CATECHOLAMIN
ES
Catecholamine's are compounds containing a catechol
moiety (a benzene ring with two adjacent hydroxyl
groups) and an amine side chain
the most important ones are:
• noradrenaline (norepinephrine), a transmitter
released by sympathetic nerve terminals
• adrenaline (epinephrine), a hormone
secreted by the adrenal medulla
• dopamine, the metabolic precursor of nor
adrenaline and adrenaline, also a
transmitter/neuromodulator in the central nervous
system
• isoprenaline (isoproterenol), a synthetic
derivative of nor adrenaline, not present in the
4. PHYSIOLOGY OF
NORADRENERGIC
TRANSMISSION
The noradrenergic neuron:
Noradrenergic neurons in the periphery
are postganglionic sympathetic neurons
whose cell bodies are situated in
sympathetic ganglia.
5. - they generally have long axons that end in
the series of varicosities strung along the
branching terminal network
These varicosities contain numerous
synaptic vesicles, which are the sites
of synthesis and release of nor
adrenaline and of co-released
mediators such as ATP and
neuropeptide Y which are stored in
vesicles and released by exocytosis.
6. NORADRENALINE SYNTHESIS
The metabolic precursor for noradrenaline
is L-tyrosine, an aromatic amino acid that
is present in the body fluids and is taken
up by adrenergic neurons.
Tyrosine hydroxylase, a cytosolic enzyme
that catalyses the conversion of tyrosine to
dihydroxyphenylalanine (dopa).
This above hydroxylation step is the main
control point for noradrenaline synthesis (rate
limiting step).
Tyrosine hydroxylase is inhibited by the
end product of the biosynthetic pathway,
noradrenaline.
8. • The tyrosine analogue α-methyltyrosine strongly
inhibits tyrosine hydroxylase and has been used
experimentally to block nor adrenaline synthesis.
• The next step, conversion of dopa to
dopamine, is catalyzed by dopa decarboxylase, a
cytosolic enzyme that is by no means confined
to catecholamine-synthesising cells.
• Dopa decarboxylase activity is not rate-limiting
for noradrenaline synthesis
• It is a relatively non-specific enzyme, and
catalyses the decarboxylation of various other L-
aromatic amino acids, such as L-histidine and L-
tryptophan, which are precursors in the synthesis
of histamine.
9. • Dopamine-β-hydroxylase (DBH) is also a
relatively nonspecific enzyme, that catalyses the
conversion of dopamine to noradrenaline.
• Many drugs inhibit DBH, including copper-
chelating agents and disulfiram (a drug used
mainly for its effect on ethanol metabolism.
• Phenylethanolamine N-methyl transferase
(PNMT) catalyses the N-methylation of nor
adrenaline to adrenaline. The main location
of this enzyme is in the adrenal medulla.
10. NORADRENALINE
STORAGE• Most of the nor adrenaline is stored in
nerve terminals or chromaffin cells is
contained in synaptic vesicles; only a little is
free in the cytoplasm under normal
circumstances.
• The concentration in the vesicles is very
high (0.3–1.0 mol/l) and is maintained by
the vesicular monoamine transporter (VMAT),
which is similar to the amine transporter
responsible for nor adrenaline uptake into the
nerve terminal.• The vesicles contain two major constituents
besides nor adrenaline, namely ATP (about four
molecules per molecule of nor adrenaline). This
substance is released along with nor
adrenaline.
11. NORADRENALINE RELEASE
• Transmitter release occurs normally by Ca2+
mediated exocytosis from varicosities on the
terminal network.
• Non-exocytotic release occurs in response to
indirectly acting sympathomimetic drugs (e.g.
amphetamine), which displace nor adrenaline from
vesicles.
• Noradrenaline escapes via the NET transporter
(reverse transport).
• Transmitter action is terminated mainly by
reuptake of nor adrenaline into nerve terminals via
• Nor adrenaline with ATP are released by exocytosis.
12. • NET is blocked by tricyclic antidepressant
drugs and cocaine.
• Noradrenaline release is controlled by
autoinhibitory feedback mediated by α2 receptors.
• Co-transmission occurs at many noradrenergic
nerve terminals, ATP and neuropeptide Y being
frequently co-released with NA.
• ATP mediates the early phase of smooth
muscle contraction in response to sympathetic
nerve activity.
• Noradrenaline, by acting on presynaptic β2
receptors, can regulate its own release, and also
that of co-released ATP.
13. Feedback control of noradrenaline (NA) release.
The
presynaptic
α2 receptor
inhibits Ca+2
influx in
response to
membrane
depolarisation
via an
action of the
βγ subunits
of the
associated G
protein on
the voltage-
dependent
14. • The depolarization of the nerve terminal causes activation of
the calcium channel.
• The calcium channel opens and ca+2 ion enters into the
cell, the calcium ions influx causes depolarization inside the
cell.
• Depolarization leads to exocytosic release of nor
adrenaline with ATP from the vesicle.
• Released NA bind to the postsynaptic receptors and
produce respective effects.
• NA bind to the α2 adrenoceptor which is auto receptor it
inhibits the NA release.
15. • Gi / Go that are the α subunit of GPCR they are
responsible for 3 activities :-
- Gi regulates the opening of potassium channel and
the inhibition of adenyl cyclase.
- Go regulates the opening of the calcium channel.
-The potassium channel opens and the K+ ions move
outside the cell this causes repolarisation of the cell. This
inhibits exocytosis of NA
- The inhibition of the adenyl cyclase inhibits the
conversion of ATP to C AMP this inhibits the opening of
calcium channel. This inhibits exocytosis of NA.
16. UPTAKE AND DEGRADATION OF
CATECHOLAMINES (nor adrenaline)
The action of released nor adrenaline is
terminated mainly by reuptake of the
transmitter into noradrenergic nerve terminals.
Circulating adrenaline and noradrenalin are
degraded enzymically, but much more slowly than
acetylcholine.
17. UPTAKE OF
CATECHOLAMINESAbout 75% of the nor adrenaline released by
sympathetic neurons is recaptured and
repackaged into vesicles.
This serves to cut short the action of the
released nor adrenaline, as well as recycling it.
The remaining 25% is captured by non-neuronal
cells in the vicinity, limiting its local spread.
These two uptake mechanisms depend on
distinct transporter molecules.
Neuronal uptake is performed by the plasma
membrane nor adrenaline transporter (generally
known as NET, the nor epinephrine transporter),
which belongs to the family of neurotransmitter
18. THE UPTAKE OF NOR ADRENALINE IS
OF 3 TYPES :-
1. AXONAL UPTAKE
2. VESICULAR UPTAKE
3. EXTRANEURONAL UPTAKE
19. AXONAL UPTAKE
An active amine pump (NET) is present at the neuronal
membrane which transports NA by a Na+ coupled
mechanism.
It takes up NA at a higher rate than Adrenaline and had
been labelled uptake-1.
The indirectly acting sympathomimetic amines like
tyramine, but not isoprenaline, also utilize this pump for
entering the neurone.
This uptake is the most important mechanism for
terminating the postjunctional action of NA.
From 75% to 90% of released NA is retaken back into
the neurone.
This pump is inhibited by cocaine, desipramine and few
20. VESICULAR UPTAKE
The membrane of intracellular vesicles has another
amine pump the ‘vesicular monoamine transporter’
(VMAT-2), which transports NA from the cytoplasm to
the interior of the storage vesicle.
The VMAT-2 transports monoamines by exchanging
with H+ ions.
The vesicular NA is constantly leaking out into the
axoplasm and is recaptured by this mechanism.
This carrier also takes up DA formed in the axoplasm
for further synthesis to NA.
Thus, it is very important in maintaining the NA content
of the neurone.
This uptake is inhibited by reserpine, resulting in
21. Extraneuronal uptake
Extraneuronal uptake of CAs (uptake-2) is carried
out by extraneuronal amine transporter (ENT or
OCT3) and other organic cation transporters
OCT1 and OCT2 into cells of other tissues.
In contrast to NET this uptake transports
Adrenaline at a higher rate than NA, is not Na+
dependent and is not inhibited by cocaine, but
inhibited by corticosterone.
It may capture circulating Adr, but is quantitatively
minor and not of physiological or pharmacological
importance.
22. METABOLIC DEGRADATION OF
CATECHOLAMINES (NOR
ADRENALINE)
- Endogenous and exogenous catecholamines are
metabolised mainly by two intracellular
enzymes:-
- Monoamine oxidase (MAO)
- Catechol-O-methyl transferase (COMT).
- MAO (of which there are two distinct
isoforms) MAO-A and MAO-B is bound to
the surface membrane of mitochondria.
- It is abundant in noradrenergic nerve
terminals but is also present in liver,
intestinal epithelium and other tissues.
- MAO converts catecholamines to their
corresponding aldehydes, which in the
periphery, are rapidly metabolised by
aldehyde dehydrogenase to the corresponding
carboxylic acid.
23.
24. • NA Converted to NM by COMT
• MAO catalyses conversion of NM to NM aldehyde
• NM aldehyde is directly converted to VMA by ADH, VMA is
the major metabolite which is excreted through urine.
• when MAO enzyme acts on the NA it gets converted to NA
aldehyde
• AR converts the NM aldehyde directly into the MHPG, which
is a minor metabolite of NA and it is excreted through urine.
• ADH converts NA aldehyde to DHMA further the DHMA is
converted to VMA by COMT
• AR catalyses the conversion of NA aldehyde to DHPG which
is catalysed to MHPG by COMT.
28. Classification of adrenoceptors
• Main pharmacological classification into α
and β subtypes, based originally on order
of potency among agonists, later on
selective antagonists.
• Adrenoceptor subtypes: – two main α-
adrenoceptor subtypes, α1 and α2, each
divided into three further subtypes (1-/2-
A,B,C)
– three β-adrenoceptor
subtypes (β1, β2, β3)
– all belong to the super
family of G protein-coupled receptors.
29. • Second messengers:
– α1 receptors activate phospholipase
C, producing inositol trisphosphate and
diacylglycerol as second messengers
– α2 receptors inhibit adenylyl cyclase,
decreasing cAMP formation
– all types of β receptor stimulate
adenylyl cyclase
30. •. • The main effects of receptor activation are as
follows:
– α1 receptors: vasoconstriction, relaxation of
gastrointestinal smooth muscle, salivary secretion
and hepatic glycogenolysis
– α2 receptors: inhibition of: transmitter release
(including nor adrenaline and acetylcholine release
from autonomic nerves); platelet aggregation;
vascular smooth muscle contraction; insulin release
– β1 receptors: increased cardiac rate and
force
– β2 receptors: bronchodilatation; vasodilatation;
relaxation of visceral smooth muscle; hepatic
glycogenolysis; muscle tremor
– β3 receptors: lipolysis and thermogenesis;
bladder detrusor muscle relaxation.
31.
32.
33. ADRENOCEPTOR AGONISTS
• Selective α1 agonists include phenylephrine and
oxymetazoline.
• Selective α2 agonists include clonidine and α-
methylnoradrenaline. They cause a fall in blood
pressure, partly by inhibition of nor adrenaline
release and partly by a central action.
• Selective β1 agonists include dobutamine.
Increased cardiac contractility may be useful
clinically, but all β1 agonists can cause cardiac
dysrhythmias.
• Selective β2 agonists include salbutamol,
terbutaline and salmeterol; used mainly for their
bronchodilator action in asthma.
• A selective β3 agonist, mirabegron, is used to
treat overactive bladder; β3 agonists promote
lipolysis and have potential in the treatment of