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NEUR3310 Neuroscience > Lecture 2: Basics of Neuropharmacology > Flashcards

Lecture 2: Basics of Neuropharmacology Flashcards

1
Q

Central Nervous System: Overview

NEURONS - 4

A
  1. CELL of the CENTRAL NS
  2. GENERATES and TRANSMITS ELECTRICAL SIGNALS electrical signals through the BRAIN AND BODY
  3. -Approx. 50% of the cells in the CNS
  4. Neurons are HIGHLY CONNECTED INTO CIRCUITS

LOOK AND LABEL NEURON

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2
Q

Central Nervous System: Overview\

What is DENDRITIC SPINES?

A

The POSTSYNAPTIC SIDE of a neuron-neuron synapse

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3
Q

Central Nervous System: Overview:

What is AXON TERMINALS?

A

PRE-SYNAPTIC side
of a neuron-neuron synapse

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4
Q

Neuron to neuron communication

(Textbook example): 4

A

1.PRESYNAPTIC neuron generates an ACTION POTENTIAL
- AXON INITIAL SEGMENT = FOUND AFTER THYE CELL BODY

  1. AP that travels down the axon to the AXON TERMINALS
  2. Axon terminals release NEUROTRANSMITTERS that
    interact with the post-synaptic neuron
  3. POST-SYNAPTIC neuron GENERATES an AP (or not).
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5
Q

Define Neuropharmacology

A

“The effect of DRUGS* on the nervous system”

Multiple types:
1. Molecular neuro..
2. Behavioural neuro..
3. Psychopharacology neuro..

= FUNCTION IS CONTEXT DEPENDENT

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6
Q

What is a DRUG?

A
  1. “A chemical substance of known structure, other than a nutrient or an essential dietary ingredient which, when ADMINISTERED to a living organism, PRODUCES A BIOLOGICAL EFFECT”
    (Rang and Dale, Pharmacology).

CAN BE
-Synthetic, naturally occurring, plants, etc.

-Endogenous “drugs”

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7
Q

What is ENDOGENOUS DRUG?

A

Endogenous substances and processes are those that originate from within the body or system such as an organism, tissue, or cell.

For example: naturally occurring pain-relieving substance like opioids, vs to opioid drugs like heroin, which are exogenously (outside the body) administered.

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8
Q

What is Molecular neuropharmacology?

A

= FUNCTION IS CONTEXT DEPENDENT

Level of SINGLE CELLS, PROTEINS, ION CHANNELS etc.

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9
Q

What is Behavioural neuropharmacology?

A

= FUNCTION IS CONTEXT DEPENDENT

  • Level of BEHAVIOUR which is the OUTPUT of ENTIRE NEURAL CIRCUITS/MANY NEURONS
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10
Q

What is Psychopharmacology?

A

= FUNCTION IS CONTEXT DEPENDENT

  • Level of MOOD and COGNITION which is the OUTPUT of entire
    CIRCUITS/BRAIN REGIONS
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11
Q

What do drugs mostly act on/TARGET?

A

— There are exceptions,

but DRUGS mostly act on TARGET PROTEINS

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12
Q

The 4 major target proteins are:

A
  1. Receptors
  2. Ion channels
  3. Enzymes
  4. Transporters
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13
Q

How are TARGET PROTEINS EXPRESSED? HOW? -2

A

The target proteins are EXPRESSED ALONG THE CELL MEMBRANE of the neuron (cell body, dendrites, axons)

  1. DIFFERENTIAL EXPRESSION
  2. DENSITY
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14
Q

What is a Receptor?

A

“…a PROTEIN MOLECULE whose
- FUNCTION is to RECOGNISE and RESPOND to ENDOGENOUS CHEMICAL SIGNALS.

  • Other
    MACROMOLECULES with which DRUGS INTERACT to
    PRODUCE THEIR EFFECTS are known as ‘drug
    targets.’
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15
Q

What is AFFINITY?

in receptors?

A

Affinity- Probability of ligand molecule binding to a receptor at a particular concentration

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16
Q

What is SELECTIVITY?

in receptors?

A

Selectivity- Degree that a drug affects a specific site relative to others.

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17
Q

Agonist vs Antagonist

In receptors?

A

Agonists: A chemical substance which “activates” a receptor

Antagonist: A chemical substance that binds to
a receptor but does not activate it. Instead, it
blocks the effect of agonists on that receptor.

— Competitive and non-competitive antagonist

— Allosteric agonist + antagonist

18
Q

Protein Targets for Drugs: Receptors…

What the ways and What are the Steps?

A

If receptor is ANTAGONIST:
1 — ANTAGONIST
2 — Molecule to receptor
3 — NO EFFECT
— ENDOGENOUS MEDIATORS BLOCKED

If receptor is AGONIST/INVERSE AGONIST
— molecule to receptor
then 2 ways

  1. DIRECT
    —- Ion channel opening/closing
  2. TRANSDUCTION MECHANISMS***
    then 3 Ways
  3. —— ENZYME ACTIVATION/INHIBITION
  4. —— ION CHANNEL MODULATION
  5. —— DNA TRANSCRIPTION
19
Q

What are ION CHANNELS?

A

1.Ion channels allow for the movement of ions
into and out of membranes

  1. Important for NEURON HOMEOSTASIS and
    ACTION POTENTIAL PROPAGATION.
  2. Most ion channels are “gated” and have a
    specific opening mechanism
    -E.g. Voltage-gated and ligandgated
20
Q

Most ION CHANNELS are “GATED” and have a
SPECIFIC OPENING MECHANISIM… EXPLAIN

A
  1. Ligand-gated and voltage-gated ion channels
  2. play a large ROLE in the FUNCTION and ACTIVITY of NEURONAL and NON-NEURONAL CELLS in the NERVOUS SYSTEM
21
Q

Ligand-gated vs Voltage Gated ion channels…How do they work?

A
  1. Ligand-gated ion channels open when a LIGAND BINDS to it
  2. Voltage-gated ion channels open when the
    VOLTAGE of the membrane REACHES A CERTAIN VALUE
22
Q

Protein Targets for Drugs: Ion Channels

2 PATHWAYS

A

PATHWAY 1:
1. BLOCKERS
—— 2. PERMEATION BLOCKED
—— Ion channel blockers block the pores and
prevent ion movement

PATHWAY 2:
1. MODULATORS
—— 2. INCREASED OR DECREASED OPENING PROBABILITY
—— Ion channel modulators DON’T BLOCK the port,
but they AFFECT THE FUNCTION of the ion channel
(E.g. opening/closing)

23
Q

What are enzymes?

What do they do?

A

There are several enzymes in the nervous
system

that have an IMPORTANT ROLE:
- AT THE SYNAPSE
- and NEURAL TRANSMISSION

24
Q

Protein Targets for Drugs: Enzymes

What are the types of ENZYMES/drug?
What is the Pathway? 3

A
  1. INHIBITOR = Normal interaction inhibited
  2. FALSE SUBSTRATE = Abnormal metabolite produced
  3. PRODRUG = Active drug produced
25
Q

What is Monoamine oxidase?

Protein Targets for Drugs: Enzymes

A

enzyme

  1. Monoamine oxidase, for example, is
    important for SEROTONIN, NOREPINEPHRINE AND DOPAMINE.
  2. Monoamine oxidase INHIBITORS (MAOIs) were the ‘first class’ of ANTIDRESSANTS DEVELOPED.
26
Q

What are Transporters?
ROLE, What do they Require? Job?
3

A
  1. Transporters also FACILITATE THE MOVEMENT OF IONS AND SMALL ORGANIC MOLECULES ACROSS THE MEMBRANE.
  2. In many cases, they RELY ON ‘ATP’ TO MOVE THE SUBSTRATE ACROSS ITS ELECTROCHEMICAL GRADIENT.
    —- -Active transport
    — -Secondary active transport
  3. Transporters play an important ROLE IN THE REUPTAKE OF NEUROTRANSMITTERS AT THE SYNAPSE.
27
Q

Protein Targets for Drugs: Transporters

The different ways and Pathways….

A
  1. NORMAL TRANSPORT
    - the way transported facilitates movement across the membrane
  2. INHIBITOR
    (on the transporter or external substance blocking the entrance)
    - TRANSPORT BLOCKED
  3. FALSE SUBSTRATE
    - ABNORMAL COMPOUND ACCUMULATED.
28
Q

Understanding Ion Channels and Receptor Expression…

found? role? consequence?

A
  1. Ion channels FOUND in EVERY MICRODOMAIN OF THE NEURON
  2. play an IMPORTANT ROLE in
    FORWARD AND BACKWARD PROPAGATION OF ELECTRIC POTENTIALS IN NEURONS.
  3. As a result, DRUGS/TOXINS etc that AFFECT ION CHANNELS can EFFECT MULTIPLE NEURONAL FUNCTIONS.
29
Q

What is the Synapse?

A

The synapse is the SPACE BETWEEN THE PRE-SYNAPTIC AND POST-SYNAPTIC NEURON/CELLS.

30
Q

Drug targets- The synapse

PROTEIN TARGETS AT THE SYNAPSE:

A
  1. Receptors
  2. Transporters
  3. Ligand-gated ion channels
  4. Voltage-gated ion channels
  5. Enzymes
31
Q

Explain Astrocytes … Drug targets- The tripartite synapse

A

ASTROCYTES often EXTEND END FEET THAT SURROUND A NEURONAL SYNAPSE.

Astrocyte END FEET ALSO RELEASES CHEMICALS AND HAVE ION CHANNELS RECEPTORS, etc

32
Q

Drug targets- The quadpartite synapse

UNDERSTANDING MICROGLIA

A
  1. Microglia = described as the
    IMMUNE CELLS OF THE BRAIN
  2. -Microglia ALSO HAVE A ROLE AT HE SYNAPSE
  3. -Microglia EXPRESS TRANSPORTERS, ION CHANNELS AND RECEPTORS
  4. -ThereforeDRUGS CAN AFFECT MULTIPLE CELLS AT A SYNAPSE, …. “its not as simple
    as a pre and post-synaptic neuron”

“ARTICLE: Increased synapse elimination by microglia in schizophrenia patient-derived models of synaptic pruning”

33
Q

Drug targets- The quadpartite synapse

UNDERSTAND EMBRYONIC AND EARLY POSTNATAL VS. POSTNATAL VS ADULT

MICROGLIA LIFE

A
  1. EMBRYONIC AND EARLY POSTNATAL
    - Activation
    - Division
    - Recruitment
  2. POSTNATAL
    - Synaptic Pruning and Maturation
  3. ADULT
    - Basal Transmission and PLasticity

SLIDE 17

34
Q

Understanding Synapses: They can be EITHER ELECTRICAL OR CHEMICAL …EXPLAIN

  • Characteristics of chemical synapses.
A

— Synapses can be chemical or
electrical

  1. Chemical synapses:
    - MOST STUDIED
    - arguably the MOST COMMON
    - FORMS INDIRECT COMMUNICATION
  2. Electrical synapses
    - commonly known as GAP JUNCTIONS in
    the nervous system
35
Q

ELECTRICAL SYNAPSES…7

CHARACTERISTICS AND HOW DOES IT WORK?

A

HOW IT WORKS?
1. Protein channel that ALLOWS BIDIRECTIONAL FLOW OF IONS,
2. METABOLITES,
3. ‘2ndary’ MESSENGERS +
SMALL MOLECULES

  1. DIRECT COMMUNICATION BETWEEN NEURONS
  2. NO DELAY IN TRANSMISSION
  3. ALLOWS CELLS/CIRCUITS TO COUPLE WITH EACH OTHER
  4. Composed of ‘2 HEMICHANNELS’
36
Q

ELECTRICAL SYNAPSES..
Vertebraes vs invertebraes

Pannexin vs Conexin

A
  1. In vertebrates,
    — the PROTEIN CONNEXIN FORMS THE HEMICHANNELS
  2. In invertebrates,
    — the PROTEIN INNEXIN FORM HEMI CHANNELS
  3. PANNEXIN has been identified in
    MAMMALIAN NEURONS, but is LESS COMMON THAN CONNEXIN.
37
Q

Location of Electrical Synapses…3

A
  1. Occur at DIFFERENT LOCATIONS ACROSS THE NEURON
  2. SOME synapses can CONTAIN BOTH CHEMICAL + ELECTRICAL SYNAPSES.
    synapses
    = ”Mixed synapse”
  3. LOCATION OF ELECTRICAL SYNAPSE =
    will have an EFFECT ON the
    ELECTRICAL ACTIVITY FOR BOTH NEURONS!!
38
Q

Location of Electrical Synapses…

WHAT ARE THE 4 MAIN TYPES FOUND?

A
  1. Dendro=dendritics synapse
  2. Somato-somatic synapse
  3. Axo-axonic synapse
  4. Mixed Synapse

LOOK AT THE IMAGE, DRAW AND UNDERSTAND THEM

39
Q

UNDERSTANDING “Volume and pure spill over transmission”

A
  1. In specific neurons and circuits,
    excess neurotransmitters,
    molecules, etc, is released that
    “escapes” the synapse
  2. The excess neurotransmitter,
    molecules, etc, can then affect
    cells that are nearby
  3. Volume transmission (VT) is a
    widespread mode of intercellular
    communication that occurs in the
    extracellular fluid (ECF) and in
    the cerebrospinal fluid (CSF) of
    the brain with VT signals moving
    from source to target cells via
    energy gradients leading to
    diffusion and convection (flow)
40
Q

What is PURE SPILL OVER TRANSMISSION?

A

Pure spill over transmission is
similar, but is where the
COMMUNICATION BETWEEN 2 CELLS IS SOLEY DUE TO THE EXCESS RELEASE OF A NEUROCHEMICAL, MOLECULE etc.

To date, there are very few
examples of pure spill over in the
nervous system

41
Q

Look at Diagram
Volume and pure spillover transmission

parallel fibre, Purkinje cell, climbing fibre…bergmann glia…interneuron

A

SLIDE 23

NEUR3310 Neuroscience (18 decks)

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