1. BY
ADESEJI, Wasiu Adebayo
ADELEYE, Olufunto Omodele
EJIMKONYE, Benjamin C.
ADIGUN, Foyeke Muniratu
ADETUNJI, Opeyemi Adebola
ANA 808 (ADVANCED NEUROANATOMY)
DEPARTMENT OF ANATOMY,
UNIVERSITY OF ILORIN.
Lecturer: Dr. M.S. Ajao
3. Introduction
Neuropharmacology is the study of how drugs affect cellular function in
the nervous system, and the neural mechanisms through which they
influence behavior.
Neuropharmacology is a very broad region of science that encompasses
many aspects of the nervous system from single neuron manipulation to
entire areas of the brain, spinal cord, and peripheral nerves.
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4. Neuropharmacological Agents
Drugs or substances that alter processes controlled by the nervous
system.
There are two categories of neuropharmacologic agents:
Peripheral nervous system drugs
Central nervous system drugs
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6. Branches of Neuropharmacology
Molecular Neuropharmacology
Molecular neuropharmacology involves the study of neurons and their
neurochemical interactions, with the overall goal of developing drugs that
have beneficial effects on neurological function.
Behavioral Neuropharmacology
Behavioral neuropharmacology focuses on the study of how drugs affect
human behavior (neuropsychopharmacology), including the study of how
drug dependence and addiction affect the human brain (Everitt and Robbins,
2005).
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7. Branches of Neuropharmacology
Both of these fields are closely connected, since both are concerned with
the interactions of neurotransmitters, neuropeptides, neurohormones,
neuromodulators, enzymes, second messengers, co-transporters, ion
channels, and receptor proteins in the central and peripheral nervous
systems
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8. Brief History
Before the 20th century, the scientific knowledge neuropharmacology was
not existent.
In the early part of the 20th century, scientists were able to figure out a
basic understanding of the nervous system and how nerves communicate
between one another.
In the 1930s, phenothiazine was found to have sedative effects and a little
beneficial effect on patients with Parkinson’s disease.
In the late 1940s and early 1950s, scientists were able to identify specific
neurotransmitters, such as norepinephrine, dopamine, and serotonin.
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9. Brief History
In the 1950s, scientists also became better able to measure levels of
specific neurochemicals in the body and thus correlate these levels with
behavior (Wrobel, 2007).
The invention of the voltage clamp in 1949 allowed for the study of ion
channels and the nerve action potential.
These two major historical events in neuropharmacology allowed
scientists not only to study how information is transferred from one
neuron to another but also to study how a neuron processes this
information within itself.
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10. Neurochemical Interactions
General process
Depolarization of neuron leading to an action potential.
Transmission of impulse down axon
Release of neurotransmitter from axon terminal
Binding of neurotransmitter to receptor on post-synaptic cell
Post-synaptic cell changes action
Muscle relaxes or contracts
Glands secrete or stop secreting
Neurons fire more often or less often
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12. Steps of Synaptic Transmission
Transmitter synthesis
Transmitter Storage (vesicles)
Release of Transmitter
Only small number of vesicles release
Receptor Binding (reversible)
Termination of Transmission
Reuptake
Enzymatic degradation
Diffusion(slow, usually doesn’t happen in vivo)
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13. Actions of Neuropharmacological Agents
Alter axonal conduction
Local anesthetics
Alter synaptic Transmission
Affect receptors
If drug causes same effect as natural process: receptor activation
If drug reduces or causes opposite: receptor deactivation
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14. Action on Transmitter Synthesis
Drugs can
Increase transmitter synthesis
Decrease transmitter synthesis
Cause synthesis of different transmitter that is more effective than the natural
Theoretical: cause synthesis of ineffective transmitter
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15. Action on Storage and Release
Storage: drugs can interfere with storage
Less transmitter stored less released
Transmitter release: drugs can
Promote release
Inhibit release
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16. Action on Receptor Binding
Drug can
Bind directly to receptors and activate them: Agonists
Bind to the same site on the receptor protein as the agonist, preventing
activation of the receptor: Competitive Antagonists
Bind to a receptor protein on a different site than that of the agonist, but
causes a conformational change in the protein that does not allow activation:
Non-competitive antagonist
Bind to receptor and enhance activation by natural transmitter
No special name
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17. Action on Termination of Transmitter
Block Reuptake
Reuptake inhibitors
Inhibition of enzymatic degradation
Both cause more increased transmitter action
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18. Acetylcholine
Synthesized in presynaptic terminal from
choline and Acetylcoenzyme A
Stored in vesicles and released with AP
Binds to receptors on postsynaptic cell
Dissociates
Is broken down by acetylcholinesterase on
the post-synaptic cell membrane
Choline is re-absorbed by neuron to
synthesize more ACh
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19. Cholinergic Receptors
All receptors that mediate responses to acetylcholine
Muscarinic, Nicotinic-M, Nicotinic-N
Adrenergic Receptors
All receptors that mediate responses to epinephrine and norepinephrine
Alpha-1, alpha-2, beta-1, beta-2
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20. black widow spider venom
stimulates release of Ach
botulinum toxin
blocks release of ACh
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curare
blocks ACh nicotinic receptors
insecticides
AChE inhibitors
atropine as antidote
blocks muscarinic receptors
21. Alzheimer’s disease
loss of ACh neurons in
the basal nucleus of Meynert
Aricept—ACh agonist
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22. GABA
GABA - GABAergic
Major NT in brain inhibitory system
Receptor subtypes
GABAA - controls Cl- channel
GABAB - controls K+ channel
Degradation by GABA-T
GABA aminotransferase ~
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23. GABA Synthesis
GABA is synthesized in the brain. It is synthesized from glutamate using
the enzyme L-glutamic acid decarboxylase (GAD) and pyridoxal
phosphate (which is the active form of vitamin B6) as a cofactor.
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26. Addiction
Physiological need for the drug
May or may not include “craving”
Craving is also referred to as
psychological dependence
Repeated activation of DA reward system
(nucleus accumbens) leads to down-
regulation, decreased activity— the drug
is needed to restore normal activity.
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Repeated activation of DA reward system
(nucleus accumbens) leads to down-
regulation, decreased activity— the drug
is needed to restore normal activity.
Prefrontal cortex inputs to nucleus
accumbens are important mediators of
psychological dependence.
Antihistamines are examples of
addiction without craving
Marijuana is an example of craving
without addiction
27. Withdrawal
Acute withdrawal—operation of
compensated nervous system in the
absence of the drug that produced the
compensatory response
For drugs of abuse, typically anhedonia
or depression. My be severe, such as
seizures.
Post-acute withdrawal—Less well
understood
Reflects long-term changes in the
nervous
system probably related to craving.
Similar to learning.
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PAW also involves pre-frontal cortex
which is responsible for regulating
“impulsivity,” and which provides
glutaminergic input to the nucleus
accumbens.
Evidence suggests that glutamate
dysregulation is an important factor
in addiction and withdrawal, and is
likely involved in post-acute
withdrawal, psychological
dependence and relapse.
28. Endogenous Opiates
Morphine-like neurotransmitters: Endorphins and enkephalins
Important for control of pain
Also activate DA reward systems
released in response to intense physical
activity—e.g., runner’s high
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34. Heroin
Heroin effective at opiate receptors in the brain after being converted to
morphine
Heroin, but not morphine, able to easily cross blood-brain barrier, so
heroin is drug of abuse
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36. References
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.
Wrobel, S. (2007). Science, serotonin, and sadness: the biology of antidepressants: A series for
the public. The FASEB Journal 21 (13): 3404–17.
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This black box method, wherein an investigator would administer a drug and examine the response without knowing how to relate drug action to patient response, was the main approach to this field.
scientists were able to identify specific neurotransmitters, such as norepinephrine (involved in the constriction of blood vessels and the increase in heart rate and blood pressure), dopamine (the chemical whose shortage is involved in Parkinson’s disease), and serotonin (soon to be recognized as deeply connected to depression).
