1.CNS NEUROTRANSMITTERS AND MoA OF CNS DRUGS

Question 1

How do drugs that act on the CNS produce their effects?

Answer 1

By directly interacting with receptors or modifying the activities of endogenous chemical mediators on their receptors.

Question 2

How are non-selective CNS drugs classified?

Answer 2

According to whether they produce CNS depression or stimulation

Question 3

How is communication done between neurons?

Answer 3

Through chemical mediators known as; neurotransmitters, neurohormones, neuromodulators and neuromediators.

A given nerve cell most commonly releases only one type of neurotransmitter, but most cells contain receptors for multiple neurotransmitters

Question 4

What is a neurotransmitter?

Answer 4

A neurotransmitter is a chemical messenger released from a neuron at an anatomically specialised junction (synapse) and that diffuses across a narrow cleft (synaptic cleft) to affect one or sometimes two postsynaptic neurons, a muscle cell, or other effector cell

Question 5

What is a neuromodulator?

Answer 5

A neuromodulator is a chemical messenger released from a neuron that affects groups of neurons, or effector cells that have the appropriate receptors
The neuromodulator modifies the activity of the target neurons or effector cells
It may or may not be released at synaptic sites
The release may be local so that only nearby neurons or effectors are influenced, or may be more widespread

Question 6

What is a neurohormone?

Answer 6

A neurohormone is a chemical messenger that is released by a neuron into the circulation and which may therefore exert its effects on distant peripheral targets

Question 7

What is a neuromediator?

Answer 7

A neuromediator is a chemical messenger released from a neuron that participates in the elicitation of the postsynaptic response to a neurotransmitter

Question 8

Gamma aminobutyric acid (GABA):

Answer 8

The major inhibitory neurotransmitter in the CNS (reduces excitability of neurons)

Question 9

Glycine:

Answer 9

The other inhibitory amino acid neurotransmitter in the CNS

Question 10

Glutamate:

Answer 10

The primary excitatory amino acid neurotransmitter in the CNS (increases excitability of neurons)

Question 11

Aspartate:

Answer 11

The other excitatory amino acid neurotransmitter in the CNS

Question 12

Dopamine:

Answer 12

Involved in the control of movement, control of functions such as emotion and visceral function and inhibits release of prolactin

Question 13

Norepinephrine (noradrenaline):

Answer 13

Involved in memory, attention, information processing, emotions, arousal, energy, psychomotor function, movement, blood pressure and heart rate regulation, nociception, and bladder emptying

Question 14

Epinephrine (adrenaline):

Answer 14

Involved in attention, blood pressure and heart rate regulation

Question 15

Serotonin:

Answer 15

Stimulates release of growth hormone, adrenocorticotrophic hormone and prolactin; regulates circadian rhythms; regulation of food intake & satiation; control of visceral functions, mood control and nociception

Question 16

Histamine:

Answer 16

Involved in arousal, biorhythms, pain control, temperature regulation, and regulation of food and water intake

Question 17

Acetylcholine:

Answer 17

Involved in control of voluntary movement, regulation of autonomic nervous system target organs (eye, salivary gland, gastro-intestinal tract, heart, sweat glands) and cognitive functions

Question 18

Nitric oxide:

Answer 18

Involved in memory and pain modulation

Question 19

Adenosine triphosphate:

Answer 19

Mediates contraction of urinary bladder, vas deferens and blood vessels, relaxation of intestine and some blood vessels, and it is involved in nociceptive responses

Question 20

Adenosine:

Answer 20

Inhibitory neurotransmitter that has sedative, anticonvulsant and neuro-protective effects

Question 21

Neuropeptides

Answer 21

Substance P, calcitonin gene related peptide, neurotensin, enkephalins, endorphins, vasopressin, oxytocin, insulin, gastrin and somatostatin

Functions: Modulate the release or action of neurotransmitters (neuromodulation), and are involved in pain modulation, cardiovascular system control and stress responses

Question 22

Drugs that exert their effects on neurotransmitter receptors:

Answer 22

①Endocannabinoid
②Melatonin
③Nicotine

Question 23

MECHANISMS OF ACTIONS OF DRUGS ACTING ON THE CNS❔

Answer 23

①Actions on ion channels
②Actions on synthesis, uptake, metabolism and activity of chemical mediators

Question 24

ACTIONS ON ION CHANNELS

Answer 24

Some drugs act through inhibiting opening of selective ion channels or facilitation of their opening
The main ion selective channels present on neuronal cells are: Na+, K+, Ca2+ and Cl-

Question 25

DRUGS THAT AFFECT SODIUM CHANNELS

Answer 25

Some drugs act through blocking Na+ channels (i.e. inhibit opening of Na+ channels) thereby reducing nerve excitability. Examples include local anesthetics and some anti-seizure drugs (e.g. phenytoin)

Question 26

DRUGS THAT AFFECT CHLORIDE CHANNELS

Answer 26

Facilitate opening of the Cl- channel resulting in Cl- influx. This causes hyperpolarisation (reduced excitability of neurons)
The chloride channel is closely linked to the neurotransmitters GABA and glycine

Question 27

DRUGS THAT BLOCK CALCIUM CHANNELS

Answer 27

Drugs that block calcium channels reduce neuronal excitation
Example: Ethosuximide used in treatment of absence seizures

Question 28

DRUGS THAT ACTIVATE POTASSIUM CHANNELS

Answer 28

Drugs that activate potassium channels produce hyperpolarisation with resultant inhibition of neuronal excitation

Examples: Inhalational and most intravenous general anaesthetic agents

Question 29

ACTIONS ON SYNTHESIS, UPTAKE, METABOLISM AND ACTIVITY OF CHEMICAL MEDIATORS

Answer 29

Most pharmacological manipulations relevant to neuropharmacology target synaptic activity or physiological processes directly related to synaptic activity

Question 30

MECHANISMS INVOLVING CHEMICAL MEDIATORS

Answer 30

①Interference with the synthesis of chemical mediator e.g. through inhibition of enzymes involved in synthesis
②Interference with chemical mediator uptake mechanisms (one of the mechanisms for terminating neurotransmitter action is through uptake of the neurotransmitter into the presynaptic cell via transport proteins)
③Inhibition of the enzymes involved in the degradation of chemical mediators. This results in increased availability of the chemical mediator to act on postsynaptic receptors.
④Alteration of presynaptic release of neurotransmitters
⊛Some drugs can displace and cause release of neurotransmitter from presynaptic stores without depolarization
⊛Some drugs may act as false neurotransmitters. They utilize the synthetic and storage capacity of a neuron with resultant formation and release of a false transmitter.
⑤Inhibition of release of the chemical mediator
⑥Blocking receptors on which the chemical mediator binds (i.e. antagonist activity)
⑦Activation of receptors on which the chemical mediator acts (i.e. agonist activity)

Question 31

SPECIFICITY AND SELECTIVITY OF CNS DRUG ACTIONS

Answer 31

SPECIFICITY: In this case, the drug acts on only one molecular target.
A drug is regarded as non-specific when it acts on more than one molecular target

SELECTIVTY of a drug depends on the concentration it achieves in various tissues. The vast majority of drugs are selective rather than specific.

Question 32

SELECTIVELY ACTING CNS DRUGS

Answer 32

They may cause either depression or excitation. Most of these drugs affect several CNS functions to varying degrees depending on the concentrations achieved in the various tissues. These drugs are classified according to their site of action or clinical uses.

Question 33

NON-SELECTIVE CNS ACTING DRUGS

Answer 33

Some drugs have very low selectivity in their CNS actions and are thus referred to as non-selective CNS acting drugs
Non-selective CNS acting drugs are classified according to whether they produce CNS depression or stimulation

Question 34

Non-selective CNS depressants (general CNS depressants)

Answer 34

These drugs depress excitable tissue at all levels of the CNS leading to:
①Decrease in the amount of mediators released by the nerve impulse
②General depression of postsynaptic responsiveness

Question 35

Non-selective CNS stimulants (General CNS stimulants)

Answer 35

Cause excitation at all levels of the CNS. Stimulation occurs through one of these two mechanisms:
①By blockade of inhibition
②By direct neuronal excitation (e.g. through increased mediator release and more prolonged mediator action)