The basic principles of neuropharmacology

Question 1

Ligand

Answer 1

Any chemical that binds to/combines with a receptor

Question 2

Receptor

Answer 2

A cellular macromolecule/assembly of macromolecules concerned directly and specifically in chemical signalling between cells

Question 3

Binding of ligands to receptors 1

Answer 3

Active process, happens due to alignment of 3D shape and biophysical properties (forces) between the ligand and binding site of the receptor

Question 4

Binding of ligands to receptors 2

Answer 4

Multiple points of interaction may be needed within a binding site for binding to occur

Hydrophobic and hydrophilic charge sites

Van der waal, electrostatic and covalent

Binding of one part of the molecule can facilitate/prevent the binding of another part (e.g through shape change)

Question 5

Endogenous ligands

Answer 5

Ligands produces naturally by the body e.g neurotransmitters

Question 6

Exogenous ligands

Answer 6

Endogenous ligands that are synthesised in the lab or modified to change their properties

Question 7

Specific binding

Answer 7

Calculated as the difference between total and nonspecific binding and reflects the amount of radiogland bound to a specific binding site

Question 8

Non-specific binding

Answer 8

Represents the nonsaturable portion of binding that is presumably not associated with specific binding under investigation

Question 9

Total binding

Answer 9

The amount of binding observed
Comprised of 2 components:
1. Specific binding (saturable)
2. Nonspecific binding

Question 10

Quantification of radioligand binding

Answer 10

When a ligand is at equilibrium with the receptors, it is quantified according to:
1. The affinity of the biding, which is expressed as a dissociation constant (Kd)
2. The amount of binding (Bmax)

Question 11

Agonists

Answer 11

Evoke (produce) effects in biological tissue
- they can be full, partial of inverse

Question 12

Antagonists

Answer 12

Do not have effects on their own biological tissue but can block effects evoked by agonists
- thus their effect is to antagonise the action of an agonist
- can be competitive and non-competitive

Question 13

When plotting quantification of agonist effect, which graph is preferred? Why?

Answer 13

The logarithmic plot is preferred for visualising concentration response relationships as it becomes easier to accurately determine the potency of the ligand

Question 14

Partial agonist

Answer 14

When it binds to a receptor it elicits only a small response because it lacks a portion of the molecule enquires for the full physiological effect/it binds to a slightly diffferent sight on the receptor
- whilst being less efficacious, they can be more potent than a full agonist

Question 15

Partial vs. Full agonist

Answer 15

• in the presence of a full agonist a partial agonist will act as a functional agonist, competing with the full agonists for the same receptor
• this reduces the ability of the full agonist to produce its maximal effect

Question 16

Receptor desensitisation

Answer 16

Repeated application of agonists can lead o receptor tolerance.
- can be overcome by increasing dose
Linear relationship —> maximal response when all receptors are occupied

Question 17

Hyperbolic relationship

Answer 17

• in most mammalian systems the relationship between occupancy and drug response is hyperbolic
• maximal responses at less than maximal receptor occupancy
  Some receptors are ‘spare’

Question 18

U-shaped curve

Answer 18

Indicates that the biological response is elicited by an agonist progressively increasing as the the agonist concentration increases - subsequently peaks at a moderate concentration

Question 19

Competitive antagonists

Answer 19

Competes with an agonist or (endogenous ligand) for the same binding site on the receptor.
The agonist does not alter the efficiency of the agonist because the same number of receptors are available to both drugs.
Hence if you increase the concentration of the agonist, it will overcome the effects of a competitive antagonist.

Question 20

Non-competitive antagonist

Answer 20

Works at a completely different binding site and alters the configuration of the receptor for the agonist. It reduces the number of receptors available for the agonist to bind to.
The potency remains the same but the efficiency is greatly reduced

Question 21

How do inert antagonists produce a behavioural response?

Answer 21

• preventing agonist action = preventing biological effect
• in the presence of constant concentration of an agonist (endogenous or exogenous) and by systematically changing the agonist concentration we can quantify the inhibitory effect of the antagonistic action on the agonist evoked response

Question 22

IC50 value

Answer 22

• half maximal inhibitory concentration
• indicated how much antagonist is needed to inhibit a biological response by half
• can be used to compare potencies of antagonists in different tissues

Question 23

Affinity (Kd)

Answer 23

Describes the strength of the binding between a ligand and its target substrate

Question 24

Efficiency

Answer 24

Measurement of the maximum biological effect that a drug can produce

Question 25

Potency

Answer 25

Refers to the amount of ligand requires to achieve or prevent a defined biological effect

Question 26

Is it possible for a ligand to be potent but also have low efficiency?

Answer 26

Yes

Question 27

Concept of selectivity

Answer 27

Most ligands have affinity to many receptors