THE PRODRUG DESIGNING FOR NEW SELECTION AND FORMULATION OF DRUG COMPATIBLE WITH API I.E. ACTIVE PHARMACUTICAL INGREDIENT, AND ITS EFFECT WHICH SHOULD BE 0. THE DRUG COMBINED WITH API AND AVILABLE IN MARKET AND DRUGS NEED TO BE COMBINE ARE ALSO DISCUSSED WITH ITS STRUCTURE AND SAR, AND COVERED AS PER THE SYLLABUS OF PCI.
PEPTIDOMIMETICS , HERE WE HAVE INCLUDED THE INTRODUCTION, CLASSIFICATION, ADVANTAGES , DISADVANTAGES, ITS METHODS PREPARATION, PRINCIPLES OD DRUG DESIGN, ITS CHEMISTRY. STEREOCHEMISTRY, SYNTHESIS AND APPLICATIONS
Introduction
Classification
Therapeutic values of peptidomimetics
Design of peptidomimetics by manipulation of amino acids
Modification of peptide backbone
Chemistry of prostaglandins, leukotrienes and thromboxanes
THE PRODRUG DESIGNING FOR NEW SELECTION AND FORMULATION OF DRUG COMPATIBLE WITH API I.E. ACTIVE PHARMACUTICAL INGREDIENT, AND ITS EFFECT WHICH SHOULD BE 0. THE DRUG COMBINED WITH API AND AVILABLE IN MARKET AND DRUGS NEED TO BE COMBINE ARE ALSO DISCUSSED WITH ITS STRUCTURE AND SAR, AND COVERED AS PER THE SYLLABUS OF PCI.
PEPTIDOMIMETICS , HERE WE HAVE INCLUDED THE INTRODUCTION, CLASSIFICATION, ADVANTAGES , DISADVANTAGES, ITS METHODS PREPARATION, PRINCIPLES OD DRUG DESIGN, ITS CHEMISTRY. STEREOCHEMISTRY, SYNTHESIS AND APPLICATIONS
Introduction
Classification
Therapeutic values of peptidomimetics
Design of peptidomimetics by manipulation of amino acids
Modification of peptide backbone
Chemistry of prostaglandins, leukotrienes and thromboxanes
Peptidomimetics are compounds whose essential elements (pharmacophore) mimic a natural peptide or protein in 3D space and which retain the ability to interact with the biological target and produce the same biological effect.
Peptidomimetics are designed to circumvent some of the problems associated with a natural peptide for example
Stability against proteolysis (duration of activity)
Poor bioavailability.
Receptor selectivity or potency (often can be substantially improved).
Sythesis of heterocyclic drugs ketoconazole and metronidazoleandhra university
A Heterocyclic compounds are those which has atoms of at least two different elements as members of its ring.
Heterocyclic chemistry is a branch of organic chemistry dealing with the synthesis, properties, and applications of these heterocycles.
ENZYME INHIBITION THE MOST IMPORTANT TOPIC FOR BIOLOGY AS WELL AS CHEMISTRY PEOPLES. WE HAVE HERE COVERED FOR THE PHARMA STUDENTS THIS WILL MAKE THEM EASY AS WE ARE COLLECTED ALL THE DATA A SINGLE PLACE WICH COVERS ALL THE COTENTS.
stereochemistry and drug action ; basic introduction about stereochemistry and stereoisomers ; pharmacokinetic and pharmacodynamics concept of stereochemistry ; easson Stedman hypothesis ; stereo selectivity criteria .
Chemistry of Prostaglandins, leukotrienes and thromboxanes(Advance medicinal ...Rohit kaushiK.
1st discovered in human serum in 1930, were found to be stimulate uterine contraction and reduce pressure.
Presumed to be synthesized by prostate gland hence the name.
Later found that synthesized in all tissue except erythrocytes.
It have a cyclopentane ring (formed from 8 to 12 carbon atoms) and two side chains, with carboxyl group on one side.
They differ In their structure due to substituent group double bond on cyclopentane ring.
Prostaglandins are structurally resemble with prostanoic acid, 20-carbon fatty acid.
Abbreviated as PG, with the class designated by a capital letter A,B,D,E,F,G,H and I, followed by a number.
PGE and PGF; 1st isolated from the biological fluids.
The letters refer to the different ring structure, except in PGG and PGH: same ring structure (cyclo endohydroperoxide).
In the same series, depending upon double bonds on the side chains designated as PGE1, PGE2, PGE3..etc
The number of double bonds varies from 1-3.
PROSTAGLANDINS RECEPTORS
They function close to the site of synthesis and are deactivated to inactive metabolites before moving into the circuation.
Act locally in very low concentration, and acts on GPCR receptors.
INHIBITION OF PROSTAGLANDINS
Corticosteroids (e.g. cortisol) prevent the formation of arachidonic acid by inhibiting the enzyme phospholipase A2.
Anti inflammatory drugs inhibits the synthesis of prostaglandins.
They block the action of cyclooxygenase.
Aspirin irreversibly inhibits cyclooxygenase.
DEGRADATION OF PROSTAGLANDINS
All eicosanoids are metabolized rapidly.
Degradation mainly occurs in liver and lung.
Two enzymes, namely 15-α-hydroxy PG dehydrogenase & 13-PG reductase, convert hydroxyl group at C15 to keto group & then to C13 and C14 dihydroderivative.
BIOCHEMICAL ACTION OF PROSTAGLANDINS
The Prostaglandins (PGE, PGA, & PGI2) are vasodilator in nature. So they decreases blood pressure.
PGE1 & PGE2 induce the symptoms of inflammation (redness, swelling, edema etc.) due to arteriolar vasodilator, and cause rheumatoid arthritis, psoriasis etc. so Corticosteroids are used to treat these conditions.
PGE2 & PGF2 are used for the medical termination of pregnancy and induction of labor.
Pyrogens (fever causing) promote PG synthesis leading to the formation of PGE2.
Migraine is also due to PGE2.
PGE2 along with histamine and bradykinin causes pain.
PGI2 inhibit platelet aggregation.
They are used in the treatment of gastric ulcers, hyoertention, thrombosis, asthma etc.
Prostaglandins are also employed in the medical termination of pregnancy, prevention of conception, induction of labor etc.
Leukotrienes are synthesized by leucocytes, mast cells, lung, heart, spleen etc. by lipoxygenase pathway of arachidonic acid.
Leukotrienes are 20- Carbon polyenoic fatty acids having a number of substituents.
Depending upon the substitutions, they are divided into LTA, LTB, LTD, and LTE.
Each type is divided into sub-groups depending upon the number of double bonds which vary from 3-5.
Leukotrienes possess
Peptidomimetics are compounds whose essential elements (pharmacophore) mimic a natural peptide or protein in 3D space and which retain the ability to interact with the biological target and produce the same biological effect.
Peptidomimetics are designed to circumvent some of the problems associated with a natural peptide for example
Stability against proteolysis (duration of activity)
Poor bioavailability.
Receptor selectivity or potency (often can be substantially improved).
Sythesis of heterocyclic drugs ketoconazole and metronidazoleandhra university
A Heterocyclic compounds are those which has atoms of at least two different elements as members of its ring.
Heterocyclic chemistry is a branch of organic chemistry dealing with the synthesis, properties, and applications of these heterocycles.
ENZYME INHIBITION THE MOST IMPORTANT TOPIC FOR BIOLOGY AS WELL AS CHEMISTRY PEOPLES. WE HAVE HERE COVERED FOR THE PHARMA STUDENTS THIS WILL MAKE THEM EASY AS WE ARE COLLECTED ALL THE DATA A SINGLE PLACE WICH COVERS ALL THE COTENTS.
stereochemistry and drug action ; basic introduction about stereochemistry and stereoisomers ; pharmacokinetic and pharmacodynamics concept of stereochemistry ; easson Stedman hypothesis ; stereo selectivity criteria .
Chemistry of Prostaglandins, leukotrienes and thromboxanes(Advance medicinal ...Rohit kaushiK.
1st discovered in human serum in 1930, were found to be stimulate uterine contraction and reduce pressure.
Presumed to be synthesized by prostate gland hence the name.
Later found that synthesized in all tissue except erythrocytes.
It have a cyclopentane ring (formed from 8 to 12 carbon atoms) and two side chains, with carboxyl group on one side.
They differ In their structure due to substituent group double bond on cyclopentane ring.
Prostaglandins are structurally resemble with prostanoic acid, 20-carbon fatty acid.
Abbreviated as PG, with the class designated by a capital letter A,B,D,E,F,G,H and I, followed by a number.
PGE and PGF; 1st isolated from the biological fluids.
The letters refer to the different ring structure, except in PGG and PGH: same ring structure (cyclo endohydroperoxide).
In the same series, depending upon double bonds on the side chains designated as PGE1, PGE2, PGE3..etc
The number of double bonds varies from 1-3.
PROSTAGLANDINS RECEPTORS
They function close to the site of synthesis and are deactivated to inactive metabolites before moving into the circuation.
Act locally in very low concentration, and acts on GPCR receptors.
INHIBITION OF PROSTAGLANDINS
Corticosteroids (e.g. cortisol) prevent the formation of arachidonic acid by inhibiting the enzyme phospholipase A2.
Anti inflammatory drugs inhibits the synthesis of prostaglandins.
They block the action of cyclooxygenase.
Aspirin irreversibly inhibits cyclooxygenase.
DEGRADATION OF PROSTAGLANDINS
All eicosanoids are metabolized rapidly.
Degradation mainly occurs in liver and lung.
Two enzymes, namely 15-α-hydroxy PG dehydrogenase & 13-PG reductase, convert hydroxyl group at C15 to keto group & then to C13 and C14 dihydroderivative.
BIOCHEMICAL ACTION OF PROSTAGLANDINS
The Prostaglandins (PGE, PGA, & PGI2) are vasodilator in nature. So they decreases blood pressure.
PGE1 & PGE2 induce the symptoms of inflammation (redness, swelling, edema etc.) due to arteriolar vasodilator, and cause rheumatoid arthritis, psoriasis etc. so Corticosteroids are used to treat these conditions.
PGE2 & PGF2 are used for the medical termination of pregnancy and induction of labor.
Pyrogens (fever causing) promote PG synthesis leading to the formation of PGE2.
Migraine is also due to PGE2.
PGE2 along with histamine and bradykinin causes pain.
PGI2 inhibit platelet aggregation.
They are used in the treatment of gastric ulcers, hyoertention, thrombosis, asthma etc.
Prostaglandins are also employed in the medical termination of pregnancy, prevention of conception, induction of labor etc.
Leukotrienes are synthesized by leucocytes, mast cells, lung, heart, spleen etc. by lipoxygenase pathway of arachidonic acid.
Leukotrienes are 20- Carbon polyenoic fatty acids having a number of substituents.
Depending upon the substitutions, they are divided into LTA, LTB, LTD, and LTE.
Each type is divided into sub-groups depending upon the number of double bonds which vary from 3-5.
Leukotrienes possess
The signal transduction pathway uses a network of interactions within cells, among cells, and throughout plant.
The external signals that affect plant growth and development include many aspects of the plant’s physical, chemical, and biological environments. Some external signals come from other plants.
Many signals interact cooperatively and synergistically with each other to produce the final response. Signal combinations that induce such complex plant responses include red and blue light, gravity and light, growth regulators and mineral nutrients .
For example the overall regulation of seed germination involves control by both external factors and internal signals.
Assignment on Need of cell signaling, Steps in cell signaling, Intercellular signaling pathways, Types of intercellular signaling pathways, Intracellular signaling pathways, Receptors, Intercellular and intracellular signaling pathways. Classification of receptor family and molecular structure ligand gated ion channels; Gprotein coupled receptors, tyrosine kinase receptors and nuclear receptors.
1. INTRODUCTION
2. WHAT IS A RECEPTOR
3. HISTORY
4. CONCEPT OF CELL SIGNALLING
5. RECEPTOR SUPER FAMILIES
6. GPCRs- SIGNAL TRANSDUCTION & ITS SECOND MESSENGERS
Total synthesis of quinine Historical PerspectiveRahul Patil PhD
Malaria, Quinine, Total Synthesis, R B Woodward, Gilbert Stork, Synthesis of Natural Product, the 150-year long quest for synthesis and structure determination of Quinine.
DERIVATION OF MODIFIED BERNOULLI EQUATION WITH VISCOUS EFFECTS AND TERMINAL V...Wasswaderrick3
In this book, we use conservation of energy techniques on a fluid element to derive the Modified Bernoulli equation of flow with viscous or friction effects. We derive the general equation of flow/ velocity and then from this we derive the Pouiselle flow equation, the transition flow equation and the turbulent flow equation. In the situations where there are no viscous effects , the equation reduces to the Bernoulli equation. From experimental results, we are able to include other terms in the Bernoulli equation. We also look at cases where pressure gradients exist. We use the Modified Bernoulli equation to derive equations of flow rate for pipes of different cross sectional areas connected together. We also extend our techniques of energy conservation to a sphere falling in a viscous medium under the effect of gravity. We demonstrate Stokes equation of terminal velocity and turbulent flow equation. We look at a way of calculating the time taken for a body to fall in a viscous medium. We also look at the general equation of terminal velocity.
Observation of Io’s Resurfacing via Plume Deposition Using Ground-based Adapt...Sérgio Sacani
Since volcanic activity was first discovered on Io from Voyager images in 1979, changes
on Io’s surface have been monitored from both spacecraft and ground-based telescopes.
Here, we present the highest spatial resolution images of Io ever obtained from a groundbased telescope. These images, acquired by the SHARK-VIS instrument on the Large
Binocular Telescope, show evidence of a major resurfacing event on Io’s trailing hemisphere. When compared to the most recent spacecraft images, the SHARK-VIS images
show that a plume deposit from a powerful eruption at Pillan Patera has covered part
of the long-lived Pele plume deposit. Although this type of resurfacing event may be common on Io, few have been detected due to the rarity of spacecraft visits and the previously low spatial resolution available from Earth-based telescopes. The SHARK-VIS instrument ushers in a new era of high resolution imaging of Io’s surface using adaptive
optics at visible wavelengths.
Earliest Galaxies in the JADES Origins Field: Luminosity Function and Cosmic ...Sérgio Sacani
We characterize the earliest galaxy population in the JADES Origins Field (JOF), the deepest
imaging field observed with JWST. We make use of the ancillary Hubble optical images (5 filters
spanning 0.4−0.9µm) and novel JWST images with 14 filters spanning 0.8−5µm, including 7 mediumband filters, and reaching total exposure times of up to 46 hours per filter. We combine all our data
at > 2.3µm to construct an ultradeep image, reaching as deep as ≈ 31.4 AB mag in the stack and
30.3-31.0 AB mag (5σ, r = 0.1” circular aperture) in individual filters. We measure photometric
redshifts and use robust selection criteria to identify a sample of eight galaxy candidates at redshifts
z = 11.5 − 15. These objects show compact half-light radii of R1/2 ∼ 50 − 200pc, stellar masses of
M⋆ ∼ 107−108M⊙, and star-formation rates of SFR ∼ 0.1−1 M⊙ yr−1
. Our search finds no candidates
at 15 < z < 20, placing upper limits at these redshifts. We develop a forward modeling approach to
infer the properties of the evolving luminosity function without binning in redshift or luminosity that
marginalizes over the photometric redshift uncertainty of our candidate galaxies and incorporates the
impact of non-detections. We find a z = 12 luminosity function in good agreement with prior results,
and that the luminosity function normalization and UV luminosity density decline by a factor of ∼ 2.5
from z = 12 to z = 14. We discuss the possible implications of our results in the context of theoretical
models for evolution of the dark matter halo mass function.
Salas, V. (2024) "John of St. Thomas (Poinsot) on the Science of Sacred Theol...Studia Poinsotiana
I Introduction
II Subalternation and Theology
III Theology and Dogmatic Declarations
IV The Mixed Principles of Theology
V Virtual Revelation: The Unity of Theology
VI Theology as a Natural Science
VII Theology’s Certitude
VIII Conclusion
Notes
Bibliography
All the contents are fully attributable to the author, Doctor Victor Salas. Should you wish to get this text republished, get in touch with the author or the editorial committee of the Studia Poinsotiana. Insofar as possible, we will be happy to broker your contact.
Richard's aventures in two entangled wonderlandsRichard Gill
Since the loophole-free Bell experiments of 2020 and the Nobel prizes in physics of 2022, critics of Bell's work have retreated to the fortress of super-determinism. Now, super-determinism is a derogatory word - it just means "determinism". Palmer, Hance and Hossenfelder argue that quantum mechanics and determinism are not incompatible, using a sophisticated mathematical construction based on a subtle thinning of allowed states and measurements in quantum mechanics, such that what is left appears to make Bell's argument fail, without altering the empirical predictions of quantum mechanics. I think however that it is a smoke screen, and the slogan "lost in math" comes to my mind. I will discuss some other recent disproofs of Bell's theorem using the language of causality based on causal graphs. Causal thinking is also central to law and justice. I will mention surprising connections to my work on serial killer nurse cases, in particular the Dutch case of Lucia de Berk and the current UK case of Lucy Letby.
Phenomics assisted breeding in crop improvementIshaGoswami9
As the population is increasing and will reach about 9 billion upto 2050. Also due to climate change, it is difficult to meet the food requirement of such a large population. Facing the challenges presented by resource shortages, climate
change, and increasing global population, crop yield and quality need to be improved in a sustainable way over the coming decades. Genetic improvement by breeding is the best way to increase crop productivity. With the rapid progression of functional
genomics, an increasing number of crop genomes have been sequenced and dozens of genes influencing key agronomic traits have been identified. However, current genome sequence information has not been adequately exploited for understanding
the complex characteristics of multiple gene, owing to a lack of crop phenotypic data. Efficient, automatic, and accurate technologies and platforms that can capture phenotypic data that can
be linked to genomics information for crop improvement at all growth stages have become as important as genotyping. Thus,
high-throughput phenotyping has become the major bottleneck restricting crop breeding. Plant phenomics has been defined as the high-throughput, accurate acquisition and analysis of multi-dimensional phenotypes
during crop growing stages at the organism level, including the cell, tissue, organ, individual plant, plot, and field levels. With the rapid development of novel sensors, imaging technology,
and analysis methods, numerous infrastructure platforms have been developed for phenotyping.
This presentation explores a brief idea about the structural and functional attributes of nucleotides, the structure and function of genetic materials along with the impact of UV rays and pH upon them.
Seminar of U.V. Spectroscopy by SAMIR PANDASAMIR PANDA
Spectroscopy is a branch of science dealing the study of interaction of electromagnetic radiation with matter.
Ultraviolet-visible spectroscopy refers to absorption spectroscopy or reflect spectroscopy in the UV-VIS spectral region.
Ultraviolet-visible spectroscopy is an analytical method that can measure the amount of light received by the analyte.
Toxic effects of heavy metals : Lead and Arsenicsanjana502982
Heavy metals are naturally occuring metallic chemical elements that have relatively high density, and are toxic at even low concentrations. All toxic metals are termed as heavy metals irrespective of their atomic mass and density, eg. arsenic, lead, mercury, cadmium, thallium, chromium, etc.
Nutraceutical market, scope and growth: Herbal drug technologyLokesh Patil
As consumer awareness of health and wellness rises, the nutraceutical market—which includes goods like functional meals, drinks, and dietary supplements that provide health advantages beyond basic nutrition—is growing significantly. As healthcare expenses rise, the population ages, and people want natural and preventative health solutions more and more, this industry is increasing quickly. Further driving market expansion are product formulation innovations and the use of cutting-edge technology for customized nutrition. With its worldwide reach, the nutraceutical industry is expected to keep growing and provide significant chances for research and investment in a number of categories, including vitamins, minerals, probiotics, and herbal supplements.
2. Receptors
• In biochemistry and pharmacology, a receptor is a protein molecule usually found embedded within the
plasma membrane surface of a cell that receives chemical signals from outside the cell.
What Are these Receptors And what do they do?
3. Receptor activation
how does an induced fit happen and what is the significance of the receptor changing shape?
messenger fits the binding site of the protein receptor it causes the binding site to change shape
5. Receptor activation
Fine balance involved in receptor, messenger binding
The bonding forces must be large enough to change the shape of the binding site, but not so strong that the
messenger is unable to leave
6.
7. Points to remember
Most receptors are membrane-bound proteins that contain an external binding site for
hormones or neurotransmitters. Binding results in an induced fi t that changes the receptor
conformation.
This triggers a series of events that ultimately results in a change in cellular chemistry.
Neurotransmitters and hormones do not undergo a reaction when they bind to receptors.
They depart the binding site unchanged once they have passed on their message.
The interactions that bind a chemical messenger to the binding site must be strong
enough to allow the chemical message to be received, but weak enough to allow the
messenger to depart.
10. Ion channel receptors
The structure of an ion channel. The bold lines show the hydrophilic sides of the channel.
11. Lock-gate mechanism for opening ion channels
Rapid response in millisecond
Synaptic transmission of signals between neurons usually involves ion channels.
Cationic ion channels Na+, K+, and Ca2+ ions.
Anionic ion channels Cl-
12. Structure of Ion channel
Nicotinic cholinergic receptor
Dextromethorphan Antitussive
Glycine receptor
Through Cl-
b-Alanine
Taurine
2-aminoethanesulfonic acid
Strychnine & Caffeine
13. Structure of Ion channel
Transverse view of Nicotinic cholinergic receptor, including transmembrane regions.
The subunits are arranged such that the second transmembrane region of each subunit faces the Central Pore Of The Ion
channel
17. Points to remember
Receptors controlling ion channels are an integral part of the ion channel. Binding of a messenger induces a
change in shape, which results in the rapid opening of the ion channel
Receptors controlling ion channels are called ligand-gated ion channel receptors. They consist
of five protein subunits with the receptor binding site being present on one or more of the
subunits.
Binding of a neurotransmitter to an ion channel receptor causes a conformational change in the
protein subunits such that the second transmembrane domain of each subunit rotates to open the
channel.
18. G-protein-coupled receptors
Activation of a G-protein-coupled receptor and G-protein
Response in Second
In general, GPCR activated by hormones (enkephalins and endorphin
) and slow-acting neurotransmitters (acetylcholine, dopamine, histamine, serotonin, glutamate, and noradrenaline)
19. Points to remember
Robert J. Lefkowitz
Howard Hughes Medical Institute and Duke University Medical Center, Durham, NC, USA
and
Brian K. Kobilka
Stanford University School of Medicine, Stanford, CA, USA
"for studies of G-protein–coupled receptors"
Today this family is referred to as G-protein–coupled receptors. About a thousand genes code for such receptors,
for example, for light, flavour, odour, adrenalin, histamine, dopamine and serotonin. About half of all medications
achieve their effect through G-protein– coupled receptors
2012 Nobel Prize in Chemistry
21. G-protein-coupled receptors
When a ligand binds to the GPCR it causes a conformational change in the GPCR, which allows it to act as
a guanine nucleotide exchange factor (GEF). The GPCR can then activate an associated G protein by exchanging
its bound GDP for a GTP.
Guanine nucleotide exchange factors (GEFs) activate monomeric GTPases by stimulating the release
of guanosine diphosphate (GDP) to allow binding of guanosine triphosphate (GTP)
•Signal transduction at the intracellular domain
of transmembrane receptors, including recognition of
taste, smell and light.
•Protein biosynthesis (a.k.a. translation) at the ribosome.
•Control and differentiation during cell division.
•Translocation of proteins through membranes.
•Transport of vesicles within the cell. (GTPases control
assembly of vesicle coats.)
GTPase-Activating Proteins
22. G-protein-coupled receptors
Muscarinic acetylcholine receptors,
or mAChRs, are acetylcholine receptors that
form G protein-receptor complexes in the cell
membranes of certain neurons[1] and other cells
M1- to M5
M1 - secretion from salivary glands and stomach
M2 - slow heart rate
M3 - vasodilation
M4 - decreased locomotion
M5 - central nervous system
Atropine - an antagonist.Carbachol
23. G-protein-coupled receptors
The adrenergic receptors (or adrenoceptors) are a class of G protein-coupled receptors that are targets of
the catecholamines, especially norepinephrine(noradrenaline) and epinephrine (adrenaline).
Epinephrine Norepinephrine
Alfuzosin is a alpha-1 blocker class. As an antagonist of
the alpha-1 adrenergic receptor, it works by relaxing the
muscles in the prostate and bladder neck, making it easier
to urinate. It is thus used to treat benign prostatic
hyperplasia
24. G-protein-coupled receptors
Opioid receptors are a group of inhibitory G protein-coupled receptors with opioids as ligands.
The endogenous opioids are dynorphins, enkephalins, endorphins, endomorphins and nociceptin.
Brain, Spinal cord and in digestive track
δ-opioid receptor Leu-enkephalin
Met-enkephalin
Deltorphins
Norbuprenorphin
μ-opioid, δ-opioid, and nociceptin receptor full agonist
Antagonists
Agonists
Buprenorphine
Trazodone
delta (δ) kappa (κ) mu (μ) Nociceptin receptor
•analgesia
•antidepressant effects
•convulsant effects
•physical dependence
•μ-opioid receptor-mediated
respiratory depression
25. G-protein-coupled receptors
There are two principal signal transduction pathways involving the G protein–coupled receptors:
•the cAMP signal pathway and
•the phosphatidylinositol signal pathway
•Class A (or 1) (Rhodopsin-like)
•Class B (or 2) (Secretin receptor family)
•Class C (or 3) (Metabotropic glutamate/pheromone)
•Class D (or 4) (Fungal mating pheromone receptors)
•Class E (or 5) (Cyclic AMP receptors)
•Class F (or 6) (Frizzled/Smoothened)
26. Glutamic acid, GABA, noradrenaline, dopamine, acetylcholine, serotonin, prostaglandins,
adenosine, endogenous opioids, angiotensin, bradykinin, and thrombin
Considering the structural variety of the chemical messengers involved, it is remarkable that the overall
structures of the G-protein-coupled receptors are so similar.
the amino acid sequences of the receptors vary quite significantly.
This implies that these receptors have evolved over millions of years from an ancient common ancestral protein
27. G-protein-coupled receptors activate signal proteins called G-proteins. Binding of a messenger results in the
opening of a binding site for the signal protein. The latter binds and fragments, with one of the subunits
departing to activate a membrane-bound enzyme
The G-protein-coupled receptors are membrane-bound proteins with seven transmembrane sections. The C -
terminal chain lies within the cell and the N -terminal chain is extracellular.
The location of the binding site differs between different G-protein-coupled receptors
The rhodopsin-like family of G-protein-coupled receptors includes many receptors that are targets for currently
important drugs.
Receptor types and subtypes recognize the same chemical messenger, but have structural differences,
making it possible to design drugs that are selective for one type (or subtype) of receptor over another.
Receptor subtypes can arise from divergent or convergent evolution.
33. Kinase-linked receptors are receptors which are directly linked to kinase enzymes. Messenger binding
results in the opening of the kinase-active site, allowing a catalytic reaction to take place.
Tyrosine kinase receptors have an extracellular binding site for a chemical messenger and an intracellular
enzymatic active site which catalyses the phosphorylation of tyrosine residues in protein substrates.
The insulin receptor is a preformed heterotetrameric structure which acts as a tyrosine kinase receptor.
The growth hormone receptor dimerizes on binding its ligand, then binds and activates tyrosine kinase
enzymes from the cytoplasm.