This document provides an overview of basic neurochemistry. It discusses the organization of the nervous system including the central nervous system made up of the brain and spinal cord, and the peripheral nervous system. It describes the basic neuron structure and function including dendrites, axons, myelin sheaths, and synapses. It explains action potentials and neurotransmission involving neurotransmitters such as serotonin, dopamine, GABA, and acetylcholine. It also summarizes neurotransmitter receptors, pathways, and the fate of neurotransmitters after release. Finally, it briefly discusses basic pharmacology principles including drug receptors, agonists, antagonists, and pharmacokinetics concepts such as absorption, distribution, metabolism, and excretion.

1. Basic Neurochemistry
Presented by:-
Mr. Dharmesh Kheni
Training team
1

2. CONTENTS
• Organization of NS
• Brain
• Spinal cord
• Peripheral nervous system
• Autonomic nervous system
• Neurotransmission
• Major neurotransmitters and
receptors
2

3. ORGANIZATION OF
NERVOUS SYSTEM
NERVOUS SYSTEM
PERIPHERAL NERVOUS SYSTEM CENTRAL NERVOUS SYSTEM
AUTONOMIC NERVOUS SYSTEM SOMATIC NERVOUS SYSTEM
BRAIN SPINAL CORD
PARASYMPATHETIC SYMPATHETIC
3

4. Brain
4

5. The Neuron
5

6. The Neuron
Soma Dendrites
Myelin
Sheath
Axon
Axon Terminals
6

7. The Neuron
• Soma (cell body) – contains nucleus,
cytoplasm, organelles
• Dendrites – receive info
• Axon – transmits info
• Myelin sheath – covers the axon to
increase transmission speed (cause
of sensory and motor disturbances in
multiple sclerosis)
7

8. Neuron
• Basic functional unit of nervous system
• Unique features of neuron:
– Excitability
– Conductivity
8

9. What is a synapse?
• A synapse is the junction between 2
neurones.
• There is a very narrow gap of about
20nm between neurones called the
synaptic cleft.
• A nerve impulse cannot cross the
synaptic cleft, so nerve impulses are
carried by chemicals called
neurotransmitters.
9

10. SYNAPSE
10

11. Action Potential/Impulse conduction
• The information in neuron is passed from one to
another in the form of nerve signal i.e. Action
potential, which is due to its unique features of
excitability and conductivity.
11

12. Action Potential
• Nerve signals are transmitted by action
potential
• Any stimulus - Mechanical
Physical
Biochemical
Sudden change in resting membrane
potential
C
12

13. 13

14. Resting membrane potential
• Normally there is an excess of positive charges
outside the cell
• Inside of the cell is negative with respect to
outside
• Called as Resting membrane potential
Normal Resting Membrane Potential is -70mv
Due to unequal no. of ions on either side of the
membrane
14

15. Resting membrane
potential
• Following are the ions which play
important role in generating resting
membrane potential :
- Sodium ions ( +vely charged)
- Potassium ions ( +vely charged)
- Chloride ions ( -vely charged)
- Organic ions ( e.g. proteins) :-vely
charged
15

16. Resting membrane potential
• Na+K+Pump actively pump 3 Na+ outside
the neuron for each 2 K+ inside the neuron.
• Thus Most of the sodium ions remain
outside of the cell and Potassium ions are
inside the cell.
• This creates negative potential inside the
resting neuron -70mv
16

17. 17

18. Action Potential
Resting stage : - 70mv
Any stimulus – Mechanical, Physical or
Biochemical
Change in resting membrane potential
(from -70mv to +30mv)
This change in RMP causes opening of
voltage gated Na+ channel
More entry of Na+ inside the neuron
Reaches Maximum electropotential +30 to 35mv
This gradual increase in charge is called as
depolarization
18

19. • Depolarization:
Each action potential begins with a sudden
change from the normal resting negative
membrane potential to a positive potential
• Repolarization :
After depolarization the action potential ends
with equally rapid change back to negative
potential
19

20. 20

21. The Synapse
• Axon terminal
releases
neurotransmitters.
• Neurotransmitters
cross the synapse
and bind to
receptors on
another neuron.
• Neurotransmitters
released, taken up
again by first
neuron.
21

22. NEUROTRANSMITTERS
• Chemicals produced by the body that
are released from the nerve endings
• Enable passage of impulses from one
neuron to another across the synapse
• Act on their specific receptors
(glycoprotein structures on the cell
membrane)
22

23. Neurotransmitter
C 23

24. Fate of Neurotransmitter
Pre Synaptic neuron
Re
u
pt
ak
rs
e
it te
Ch
sm
a
n
nn
tra
e
o
ur
ls
MAO Ne
Auto Receptor
Vesicles
tors
COMT apt ic Recep
Post Syn
Post Synaptic neuron Diffusio
n of NTs
24

25. 1.Fate of Neurotransmitter
Pre Synaptic neuron
Post Synaptic neuron
25

26. 2.Fate of Neurotransmitter
Pre Synaptic neuron
Reuptake
channel
Post Synaptic neuron
26

27. 3.Fate of Neurotransmitter
Pre Synaptic neuron
Auto Receptor
prevents further
release
Post Synaptic neuron
27

28. 4.Fate of Neurotransmitter
Pre Synaptic neuron
Reuptake
MAO Auto Receptor
channel prevents further
release
COMT
Post Synaptic neuron
28

29. 5.Fate of Neurotransmitter
Pre Synaptic neuron
Reuptake Auto Receptor
channel prevents further
release
COMT
Post Synaptic neuron
29

30. 6.Fate of Neurotransmitter
Pre Synaptic neuron
Reuptake Auto Receptor
channel prevents further
release
Post Synaptic neuron Diffusio
n of NTs
30

31. Neurotransmitters
• Excitatory :
- Stimulate neurons
e.g. Noradrenaline, Dopamine,
Histamine, Serotonin, Glutamate etc.
Acetyl-choline (neuromodulator)
• Inhibitory :
- Suppress the neurons
e.g. GABA (Gamma-Amino-Butyric-
Acid) 31

32. Neurotransmitters
• Acetylcholine – movement (respiratory
paralysis)
• Serotonin – mood, sleep, appetite, anxiety
(depression, obsessive-compulsive
disorder, panic disorder)
• Dopamine – motivation, pleasure
(schizophrenia, Parkinson’s)
• Epinephrine and Norepinephrine –
attention, anxiety, stress (epilepsy, mania in
bipolar disorder)
32

33. Serotonin
• Serotonin - 5-Hydroxytriptamine
• Also known as 5-HT
• Known to control impulse, emotion &
behaviour
• Increased levels leads to aggression
• Reduced level may induce suicidal
thoughts
• Involved in sleep & depression
33

34. Serotonin Receptors
• The serotonin receptors are called
5HT1, 5HT2, 5HT3, 5HT4, 5HT5, 5HT6 &
5HT7.
• These are further subdivided as 5HT 1A,
5HT2A,5HT1B, 5HT1D etc.
34

35. Serotonin Receptors
35

36. Serotonergic
pathways
36

37. AcetylCholine
• Acetylcholine is the major
neurotransmitter which controls
various activities like
1. contraction of skeletal muscles,
2. relaxation of cardiac muscles,
arousal,
3. reward,
4. memory,
5. short term learning
37

38. Acetylcholine
• Found in
neuromuscular
junction
• Involved in
muscle
movements
38

39. Receptors of Acetylcholine
• The receptors of Ach are of various
types & are complicated in nature
• Muscarinic & nicotinic receptors are
important
• Muscarinic receptors M1, M2, M3 …M5
• Binding of Ach with M1 M3 M5 causes
stimulatory effects whereas binding
with M2 & M4 Causes inhibitory
action.
39

40. Muscarinic
receptor
40

41. Nicotinic
Receptor
N1, N2
41

42. Cholinergic
pathways
42

43. Norepinephrine/Noradrenaline
• Noradrenaline normally produces
effects such as increased heart rate,
increased blood pressure, dilation of
pupils, dilation of air passages in the
lungs and narrowing of blood vessels
in non-essential organs. This enables
the body to perform well in stressful
situations. Increases levels of energy,
interest & Mood.
43

44. Norepinephrine/Noradrenaline
• Receptors :
Alpha receptors:
- α1 receptors
Found in the blood vessels
- α2 receptors (Auto receptor)
Beta receptors:
- β 1 receptors
Mainly found in heart
- β 2 receptors
Mainly found in bronchi
44

45. Noradrenergic
pathways
45

46. DOPAMINE
• Dopamine interacts with receptors on
some peripheral nerve fibers and many
central neurons (eg, in the substantia
nigra, midbrain, ventral tegmental area,
and hypothalamus).
• After release and interaction with
receptors, dopamine is actively pumped
back (reuptake) into the nerve terminal.
46

47. Dopamine
• Involved in movement, attention and
learning, drive, desire motivation &
pleasure/reward
• Dopamine imbalance also involved in
schizophrenia
• Loss of dopamine- producing
neurons is cause of Parkinson’s
Disease
47

48. DOPAMINE RECEPTORS
• Dopaminergic receptors are
classified as D1 through D5.
• D3 and D4 receptors play a role
in thought control (limiting the
negative symptoms of
schizophrenia); D2 receptor
activation controls the
extrapyramidal system.
48

49. D2 is primarily a post synaptic receptor
whereas D3 is believed
To be a autoreceptor
49

50. Dopaminergic
pathways
50

51. Gama Amino Butyric Acid
• It is primarily an inhibitory
neurotransmitter responsible for
Sleep, prevents anxiety & stress
signals & has an overall calming effect
on the brain.
• It has three receptors GABAA, GABAB
& GABAC
51

52. GABA receptor
complex
52

53. Gabanergic
pathways
53

54. SUBSTANCE-P
• Substance P, a peptide, occurs
in central neurons (habenula,
substantia nigra, basal ganglia,
medulla, and hypothalamus) and
is highly concentrated in the
dorsal root ganglia.
• Its release is triggered by
intense afferent painful stimuli.
54

55. NITRIC OXIDE
• Nitric oxide (NO) is a labile gas that mediates
many neuronal processes.
• It is generated from arginine by NO synthase,
an enzyme that activates soluble guanylate
cyclase by binding to Ca/calmodulin
complexes.
• Thus, neurotransmitters that increase
intracellular Ca (eg, substance P, glutamate,
acetylcholine) stimulate NO synthesis in
neurons that express NO synthetase.
• NO may be an intracellular messenger; it may
diffuse out of a cell into a 2nd neuron and
produce physiologic responses (eg, long-term
potentiation [a form of learning],
neurotransmitter release and reuptake) or
enhance glutamate (NMDA) receptor-mediated
neurotoxicity.
55

56. Glutamate & Aspartate
• They are excitatory neurotransmitters.
• Their receptors are of 2 types.
– Ionotropic
– N- Methyl D- Aspartate. (NMDA)
Alpha-amino-3-hydroxyl-5-methyl-4-isoxozole
propionic acid (AMPA)
– Metabotropic
Trans-1-aminoclycopentane1,3Dicarboxylicacid.
(Trans- ACPD)
56

57. Drugs
• Drugs which have molecules of
similar shape to transmitter
substances can affect protein
receptors in postsynaptic
membranes.
• Drugs that stimulate a nervous
system are called AGONISTS
• Drugs that inhibit a nervous
system are called
ANTAGONISTS.
57

58. NEUROTRASMISSION
• A neuron generates and propagates an
action potential along its axon, then
transmits this signal across a synapse by
releasing neurotransmitters, which
trigger a reaction in another neuron or an
effector cell (eg, muscle cells; most
exocrine and endocrine cells).
• The signal may stimulate or inhibit the
receiving cell, depending on the
neurotransmitter and receptor involved.
58

59. Blood brain barrier: A mechanism that
creates a barrier between brain tissues and
circulating blood; serves to protect the central
nervous system.
Propagation: passing of electrical impulse
within neuron by exchange of Na+ and K+
across the axonal membrane.
59

60. BASIC PHARMACOLOGY
60

61. Receptors
• Specific macromolecular components of
the cell which act as a binding site with
functional correlate to produce effect
• Situated - on the surface / inside the cell
61

62. Drug at Receptor
• Agonist : It activates a receptor to produce an effect
similar to that of the physiological signal molecule
• Antagonist : It prevents the action of an agonist on a
receptor but does not have any effect of its own
• Partial agonist : It activates a receptor to produce sub
maximal effect but antagonises the action of full
agonist.
62

63. 63

64. 64

65. Competitive antagonist
– Competes with an agonist for receptors
– High doses of an agonist can generally overcome antagonist
65

66. PHARMACODYNAMICS
• It it the quantitative study of the biological
and therapeutic effects of drugs.
• “What Drug does to the body”
66

67. PHARMACOKINETICS
• It is the study of
absorption, distribution,
metabolism and excretion
of drugs
• “What Body does to the
Drug”
67

68. Pharmacokinetics
• Absorption
How the drug is moved into blood stream from the site
of administration ?
• Distribution
How much drug is moved to various body tissues /
organs ? Depends on blood flow through tissue
• Metabolism
How the drug is altered – broken down ?
• Elimination
How much of the drug is removed from the body ?
68

69. Absorption and Bioavailability
• Absorption is the movement of drug from its
site of administration into the circulation.
• Bioavailability : Fraction of administered dose
of a drug that reaches the systemic circulation
in the unchanged form.
– Bioavailability of IV route : 100 %
69

70. Bioavailability
70

71. Half-Life
• It is a time required for 50% of
elimination of the plasma
concentration of the administered
drug.
71

72. Half Life (t1/2)
110
100
90
80
70
60
50
40
30
20
10
0
0 1 2 3 4 5 6 7 8 9
T ime (ho ur s )
72

73. DRUG EXCRETION
• Kidneys
• Lungs
• Skin
• Bile
• Milk and Saliva
73

74. FACTORS MODIFYING THE
EFFECTS OF DRUG
• Body weight
• Age
• Gender.
• Diet & environment
• Route of administration
• Emotional Factors
74

75. FACTORS MODIFYING
THE EFFECTS OF DRUG
• Genetic factors
• metabolic disturbances
• Presence of disease
• Other drug therapy
• Additive effect
• Antagonism - chemical
antagonism
75

76. 76

77. Effect of nicotine and
atropine
77

78. The Blood-Brain Barrier
78

79. The Blood-Brain Barrier
• Endothelial cells in blood vessels in
the brain fit closely together
• Only some molecules can pass
through
• Protects the brain from foreign
molecules and hormones and
neurotransmitters from other parts of
the body
• Can be damaged by infections, head
trauma, high blood pressure, etc.
79

80. The Brain
80

81. The Brain
81

82. The Brain
• Cerebral Cortex – thought, language,
reasoning, movement, sensation
• Corpus Callosum – connects the right
and left hemispheres
• Cerebellum – movement, balance
• Brainstem – breathing, heart rate
82

83. Lobes of the Brain
83

84. Lobes of the Brain
• Frontal Lobe – personality, planning,
emotion, problem solving
– Motor cortex - movement
– Broca’s area – speech production
• Parietal Lobe - touch
• Temporal Lobe – hearing
– Inferotemporal Cortex – object
recognition
– Wernicke’s area – language
comprehension
• Occipital Lobe - vision
84

85. 85