This document provides an overview of neuropharmacology and neurotransmission. It defines neuropharmacology and describes the two main branches. It explains what neurotransmission is and how it works, describing the role of neurons, neurotransmitters, and the mechanism of neurotransmission. It discusses different types of neurons, neurotransmitters like acetylcholine and dopamine, and conditions they are involved in like Alzheimer's and Parkinson's disease. The document also provides interesting facts about neurons and neurotransmitters. It concludes with a recent discovery about how endocannabinoids travel in the brain to reach receptors.
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Definition of Neuro-Pharmacology
• Neuropharmacology is the study of how drugs affect cellular
function in the nervous system, and the neural mechanisms
through which they influence behavior.[1]
• There are two main branches of Neuro-pharmacology:
*Behavioral
*Molecular[2]
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Neuro-Pharmacology
• Behavioral Neuro-Pharmacology focuses on the study of how drugs affect human
behavior (neuropsychopharmacology), including the study of how drug dependence
and addiction affect the human brain.[2]
• Molecular Neuro-Pharmacology involves the study of neurons and
their neurochemical interactions, with the overall goal of developing drugs that have
beneficial effects on neurological function.
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Neuro-Transmission
• Neuro – Neural
• Transmission – Passage, Crossing, Send, or Let through
• It is the process by which signaling molecules called neurotransmitters are released by
the axon terminal of a neuron (the presynaptic neuron), and bind to and react with
the receptors on the dendrites of another neuron (the postsynaptic neuron) a short
distance away. It is a forward movement of signaling molecules.
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A Neuron
• A specialized cell that receives information and transmits it to
other cells
• A neuron, also known as a neurone or nerve cell, is
an electrically excitable cell[3] that communicates with other
cells via specialized connections called synapses. It is the main
component of nervous tissue.
All animals except sponges and placozoans have neurons, but
other multicellular organisms such as plants do not.
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A Neuron
• It was Santiago Ramón y Cajal (1852-1934) who suggested that the neuron was the
anatomical and functional of the nervous system
• Bundle of Axons is called as a Nerve, that carry sensory information to the (CNS) and
instructions from the CNS to muscles and glands.
• The longest axons in the human body, are those of the sciatic nerve, which run from the
base of the spine to the big toe of each foot. These single-cell fibers may extend a meter
or even longer. In vertebrates, the axons of many neurons are sheathed in myelin, which
is formed by either of two types of glial cells: Schwann cells ensheathing peripheral
neurons and oligodendrocytes insulating those of the central nervous system.
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Types of Neurons:
• Neurons are typically classified into three types based on their function as,
• Sensory neurons respond to stimuli such as touch, sound, or light that affect the cells
of the sensory organs, and they send signals to the spinal cord or brain.
• Motor neurons receive signals from the brain and spinal cord to control everything
from muscle contractions to glandular output.
• Interneurons or Relay Neuron connect neurons to other neurons within the same
region of the brain or spinal cord. A group of connected neurons is called a neural
circuit.
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Neuro-Transmitters
• Neurotransmitters are endogenous chemicals that
enable neurotransmission.
• It is a type of chemical messenger which transmits
signals across a chemical synapse, such as
a neuromuscular junction, from one neuron (nerve cell)
to another "target" neuron, muscle cell, or gland cell.[8]
• Neurotransmitters are released from synaptic
vesicles in synapses into the synaptic cleft, where they
are received by neurotransmitter receptors on the target
cells.
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Neuro-Transmitters
• Ramón y Cajal (1852–1934), discovered the Synaptic cleft.
• Otto Loewi (3 June 1873 – 25 December 1961) was a
German-born pharmacologist and psychobiologist
who discovered the role of acetylcholine as an
endogenous neurotransmitter.
• Necessary for rapid communication in synapse.
• Neurotransmitters are packaged into synapticvesicles -
presynaptic side of a synapse.
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Neuromodulation:
• Neuromodulation is the physiological process by which a
given neuron uses one or more chemicals to regulate diverse populations of
neurons.
• Neuromodulators typically bind to metabotropic, G-protein coupled
receptors to initiate a second messenger signaling cascade that induces a
broad, long-lasting signal.
• This modulation can last for hundreds of milliseconds to several minutes.
Some of the effects of neuromodulators include: alter intrinsic firing
activity,[9] increase or decrease voltage-dependent currents, alter synaptic
efficacy, increase bursting activity[10] and reconfiguration of synaptic
connectivity.[11]
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Neuromodulation:
• Major neuromodulators in the central nervous system
include: dopamine, serotonin, acetylcholine, histamine, norepinephrine and
several neuropeptides. Neuromodulators can be packaged into vesicles and released by
neurons, secreted as hormones and delivered through the circulatory system.[12]
• A neuromodulator can be conceptualized as a neurotransmitter that is not reabsorbed by
the pre-synaptic neuron or broken down into a metabolite. Some neuromodulators end
up spending a significant amount of time in the cerebrospinal fluid (CSF), influencing
(or "modulating") the activity of several other neurons in the brain.[13]
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Properties Of Neurotransmitters
1) Synthesized in the presynaptic neuron.
2) Localized to vesicles in the presynaptic neuron
3) Released from the presynaptic neuron under physiological condition
4) Rapidly removed from the synaptic cleft by uptake or degradation
5) Presence of receptor on the post-synaptic neuron.
6) Binding to the receptor elicits a biologicalresponse
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Factors Regulating Neuro-Transmission
Neurotransmission is regulated by several different factors:
• The availability and rate-of-synthesis of the neurotransmitter,
• The release of that neurotransmitter,
• The baseline activity of the postsynaptic cell,
• The number of available postsynaptic receptors for the neurotransmitter to bind to, and
• The subsequent removal or deactivation of the neurotransmitter by enzymes or
presynaptic reuptake.[14][15]
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Neurotransmitters
Acetylcholine
• Acetylcholine (often abbreviated ACh) is the most common
neurotransmitter. It is located in both the central nervous and
peripheral nervous system
• Acetylcholine was the first neurotransmitter be identified in
1914
• As a neuromodulator it acts on basic autonomic and
muscular fuctions
• Sarin Gas disrupts its ability to function and often leads to
death
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Dopamine
• Generally involved in regulatory motor activity
• In the basal ganglia, involved in mood, sensory perception,
and attention
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Glutamate
• Is an excitatory neurotransmitter
• Plays a role in learning and memory
• Too much can cause seizures
• Malfunction of glutamate has also been associated
with Alzheimer's’
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Epinephrine
•Also known as adrenaline
•Causes the feeling of being
“revved up” or on edge
• Activates a “fight or flight” reaction in the
autonomic nervous system
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Serotonin
• Attention and other complex cognitive functions, such as sleep
(dreaming), eating, mood, pain regulation
• Neurons which use serotonin are distributed throughout the
brain, stomach and spinal cord
• Mood disorders
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GABA
• (Gamma-AminoButyric Acid)
• GABA is the most important and common
inhibitory neurotransmitter
• Stops the brain from becoming overexcited
• Too much may cause hallucinations
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1.Neurotransmitters are synthesized
from precursors under the influence of
enzymes
2.Stored in vesicles
3.Neurotransmitter molecules that leak
from their vesicles are destroyed by
enzymes
4.Action potential cause vesicle to fuse
with synapse and release
neurotransmitters
5.Some of it binds with auto receptor and
inhibit subsequent neurotransmitter
release
6.Rest of it bind to post
synaptic receptors.
7.Released neurotransmitters are
deactivated either by re uptake or
enzyme degradation.
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Mechanism Of Neuro-Transmission
• In response to a threshold action potential or graded electrical potential, a
neurotransmitter is released at the presynaptic terminal. The released neurotransmitter
may then move across the synapse to be detected by and bind with receptors in the
postsynaptic neuron. Binding of neurotransmitters may influence the postsynaptic
neuron in either an inhibitory or excitatory way. The binding of neurotransmitters to
receptors in the postsynaptic neuron can trigger either short term changes, such as
changes in the membrane potential called postsynaptic potentials, or longer term
changes by the activation of signaling cascades.
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Neurons stay at rest with their sodium ions
on the outside of the cell body (or soma)
and potassium ions on the inside.
Neurons are no longer at rest when
the
sodium ions on the outside of the cell
body rush in and potassium ions on the
inside rush out.
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An electrical impulse is caused
from the rushing in and out of the
ions (depolarization)
The electrical impulse races
down the axon
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Once the electrical
impulse reaches the
terminal button it
triggers the vesicles
(containing
neurotransmitters), to
move toward the bottom
of the terminal button.
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Steps in Neurotransmitter processing are:
Synthesis: Neurotransmitters are synthesized by the
enzymatic transformation of precursors.
Storage: They are packaged inside synaptic vesicles.
Release: •They are released from presynaptic terminal by
exocytosis when calcium enters axon terminal
during an action potential
•Diffuse across the synaptic cleft to
the postsynaptic membrane.
Binding: They bind to receptor proteins.
Inactivation: The neurotransmitter is degraded either by being broken down
enzymatically, or reused by active reuptake.
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Acetylcholine (Ach)
Acetylcholine was the first neurotransmitter to be discovered.
Isolated in 1921 by a German biologist named OttoLoewi.
Uses choline as a precursor - cholinergicneurotransmitter.
Used by the Autonomic Nervous System, such as smooth muscles of the heart, as an inhibitory
neurotransmitter.
Responsible for stimulation of muscles, including the muscles of the gastro-intestinal system.
Used everywhere in the brain.
Related to Alzheimer'sDisease.
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Interesting Facts about Neurons
• The speed of a nerve impulse varies with the type of nerve impulse the nervous
system is sending. Some signals such as those for muscle position, travel at speeds up
to 119.807m/s. Nerve impulses such as pain signals travel slower at 0.61m/s. Touch
signals travel at speeds of 76.2m/s.
• Messages pass CHEMICALLY between neurons, ELECTRICALLY within each
neuron.
• Each neuron has thousands of neurotransmitters waiting to cross the synapse.
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Interesting Facts about Neurons
• Is Reverse flow of signal possible? Yes it’s possible. The
transmission is called as Retrograde Transmission.
• In retrograde neurotransmission, the dendrites of the
postsynaptic neuron release retrograde neurotransmitters
(e.g., endocannabinoids; synthesized in response to a rise
in intracellular calcium levels) that signal through receptors
that are located on the axon terminal of the presynaptic
neuron, mainly
at GABAergic and glutamatergic synapses.[4][5][6][7]
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Interesting Facts about Neurons
• These are basically made up of Amino acids.
• The human brain contains an estimated 86 billion neurons. The total number of
neurotransmitters is so astronomical that we have no way of measuring it. It’s almost
comparable to counting the stars in a galaxy: we know there are vast amounts, but we can
never be sure just how many.
• Antidepressants drugs can affect neurotransmitters.
• Previously it was believed that each type of neuron released a single, unique
neurotransmitter over its lifetime. It was called as Dale’s law.
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Interesting Facts about Neurons
• Later on it was found that, Some cells change the type of neurotransmitters they release
depending on the circumstances, sometimes releasing up to five different kinds.
Scientists call this phenomenon “neurotransmitter switching.”
• Neurotransmitters can regulate your health and wellbeing.
• Alcohol raisesdopamine levels.This leads to excitement, pleasure and later addiction.
• Neurons cannot touch each other.
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Recent discovery
In a study published this week by the Proceedings of the National Academy of Sciences, researchers from RIA
and Stony Brook University show that a particular protein, known as fatty-acid-binding protein 5 (FABP5), is key to
how endocannabinoids travel from neurons to receptors in the brain. This research, led by Haj-Dahmane, was
supported by the National Institutes of Health and SUNY REACH (Research Excellence in Academic Health).
Endocannabinoids are naturally produced lipids in the brain that control numerous physiological and behaviors
functions, including emotions, stress, pain, motor control and cognition. Released from brain cells, endocannabinoids
must travel through a liquid environment to reach and activate cannabinoid receptors and produce their physiological
effects. These neurotransmitters are transported and reach their targets in the brain, which could lead to new drug
therapies to help anxiety and other negative brain functions.
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REFERENCES:
1. Yeung AWK, Tzvetkov NT, Atanasov AG. When Neuroscience
Meets Pharmacology: A Neuropharmacology Literature Analysis.
Front Neurosci. 2018 Nov 16;12:852. doi:
10.3389/fnins.2018.00852.
2. Everitt, B. J.; Robbins, T. W. (2005). "Neural systems of
reinforcement for drug addiction: from actions to habits to
compulsion". Nature Neuroscience. 8 (11): 1481–
1489. doi:10.1038/nn1579. PMID 16251991.
3. Rutecki PA (April 1992). "Neuronal excitability: voltage-
dependent currents and synaptic transmission". Journal of
Clinical Neurophysiology. 9 (2): 195–211. doi:10.1097/00004691-
199204010-00003. PMID 1375602.
4. Melis M, Pistis M (December 2007). "Endocannabinoid signaling
in midbrain dopamine neurons: more than physiology?". Current
Neuropharmacology. 5 (4): 268–
77. doi:10.2174/157015907782793612. PMC 2644494. PMID 19
305743.
5. Flores A, Maldonado R, Berrendero F (December
2013). "Cannabinoid-hypocretin cross-talk in the central nervous
system: what we know so far". Frontiers in Neuroscience. 7:
256. doi:10.3389/fnins.2013.00256. PMC 3868890. PMID 24391536.
Direct CB1-HcrtR1 interaction was first proposed in 2003 (Hilairet et
al., 2003).
6. Freund TF, Katona I, Piomelli D (July 2003). "Role of endogenous
cannabinoids in synaptic signaling". Physiological Reviews. 83 (3):
1017–66. doi:10.1152/physrev.00004.2003. PMID 12843414.
7. Ayakannu, Thangesweran; Taylor, Anthony H.; Marczylo, Timothy H.;
Willets, Jonathon M.; Konje, Justin C. (2013). "The Endocannabinoid
System and Sex Steroid Hormone-Dependent Cancers". International
Journal of
Endocrinology. 2013. doi:10.1155/2013/259676. ISSN 1687-
8337. PMC 3863507. PMID 24369462.
8. Lodish, H.; Berk, A.; Zipursky, S.L. (2000). Molecular Cell Biology:
Section 21.4Neurotransmitters, Synapses, and Impulse
Transmission (4th ed.). New York: W. H. Freeman.
54. 54
REFERENCES:
9. DeRiemer, S. A.; Strong, J. A.; Albert, K. A.; Greengard, P.;
Kaczmarek, L. K. (24–30 January 1985). "Enhancement of calcium
current in Aplysia neurones by phorbol ester and protein kinase
C". Nature. 313 (6000): 313–
316. doi:10.1038/313313a0. ISSN 0028-0836. PMID 2578617.
10. Jump up to:a b Harris-Warrick, R. M.; Flamm, R. E. (July
1987). "Multiple mechanisms of bursting in a conditional bursting
neuron". The Journal of Neuroscience. 7 (7): 2113–
2128. doi:10.1523/JNEUROSCI.07-07-02113.1987. ISSN 0270-
6474. PMC 6568948. PMID 3112322.
11. Klein, M; Kandel, E R (November 1980). "Mechanism of calcium
current modulation underlying presynaptic facilitation and
behavioral sensitization in Aplysia". Proceedings of the National
Academy of Sciences of the United States of America. 77 (11): 6912–
6916. doi:10.1073/pnas.77.11.6912. ISSN 0027-
8424. PMC 350401. PMID 6256770.
12. Marder, Eve (4 October 2012). "Neuromodulation of Neuronal
Circuits: Back to the Future". Neuron. 76 (1): 1–
11. doi:10.1016/j.neuron.2012.09.010. ISSN 0896-
6273. PMC 3482119. PMID 23040802.
13. Conlay, L. A.; Sabounjian, L. A.; Wurtman, R. J. (1992). "Exercise
and neuromodulators: Choline and acetylcholine in marathon
runners". International Journal of Sports Medicine. 13 Suppl 1:
S141–2. doi:10.1055/s-2007-1024619. PMID 1483754.[verification needed]
14. Nagatsu, T. (December 2000). "[Molecular mechanisms of
neurotransmission]". Rinsho Shinkeigaku = Clinical
Neurology. 40 (12): 1185–1188. ISSN 0009-918X. PMID 11464453.
15. Andreae, Laura C.; Burrone, Juan (March 2018). "The role of
spontaneous neurotransmission in synapse and circuit
development". Journal of Neuroscience Research. 96 (3): 354–
359. doi:10.1002/jnr.24154. ISSN 0360-
4012. PMC 5813191. PMID 29034487.
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“Quote – Don’t see life as a destination to be reached where u may think of enjoying your goals,
instead see life as a music where u don’t wait for a specific note to enjoy the whole music, u actually
enjoy every note of it.
“Enjoy every moment of life”
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