Intro To CNS

Question 0

Describe the small molecules neurotransmitters.

Answer 0

They are:

• “classical” low-molecular weight neurotransmitter substances
• there are many biochemical similarities including biosynthetic and degradation pathways.
• all of these are amines and six derived from amino acids (ACh is the exception)

Question 1

What are two major classes of neurotransmitters?

Answer 1

1) small molecules

2) peptides

Question 2

What are the small molecule neurotransmitters?

Answer 2

1) acetylcholine (ACh)
2) dopamine (DA)
3) norepinephrine (NE)
4) epinephrine
5) serotonin (5HT)
6) glutamate
7) GABA

Question 3

Describe peptide neurotransmitters.

Answer 3

• These are also “small” molecules, these are typically larger than the ‘small molecules’.
• There is an incredible diversity of peptide neurotransmitters in the brain.

Question 4

What classes are included in the peptide neurotransmitters?

Answer 4

1) opioid-type peptides (like endorphins and enkephalins)
2) gut-brain peptides (like substance P)
3) hypothalamic-releasing hormones
4) the pituitary hormones

Question 5

What is ACETYLCHOLINE?

Answer 5

• ACh is an excitatory neurotransmitter used in the CNS and PNS.
• In the PNS, ACh is used by motor neurons to trigger muscle contractions.
• In the CNS, it maintains the electro-encephalographic (EEG) signals of the cortex and plays a role in memory by maintaining neuronal excitability.

Question 6

How is Alzheimer’s disease related to ACh?

Answer 6

Alzheimer’s disease is related to the death of cholinergic (ACh-containing) neurons in the cortex.

Question 7

What are the two types of ACh receptors?

Answer 7

• 2 types of ACh receptors are : 1) muscarinic and 2) nicotinic.
• Muscarinic ACh receptors are G-protein coupled receptors
• nicotinic ACh receptors are ion channels

Question 8

What is ACh made of?

Answer 8

• ACh is made from acetyl-CoA and choline by the enzyme cholineacetyltransferase (ChAT).
• acetyl-CoA is derived from the Krebs cycle in mitochondria
• choline is only obtained from the diet and transported into neurons.

Question 9

How is ACh eliminated?

Answer 9

ACh is eliminated by the enzyme acetylcholinesterase (AChE) that breaks down the neurotransmitter into choline and acetate.

Question 10

ACh: What is an organophosphate-containing insecticides drug?

Answer 10

Malathion

Question 11

ACh: What drug are nerve gases that are irreversible AChE inhibitors?

Answer 11

Sarin

Question 12

What are used for Alzheimer’s symptoms?

Answer 12

Reversible AChE inhibitors

Question 13

What is ACh receptor agonist?

Answer 13

Nicotine

Question 14

What is a ACh receptor antagonist?

Answer 14

scopolamine

Question 15

What are CATECHOLAMINES?

Answer 15

Catecholamines are a family of neurotransmitters that contain a “catechol” nucleus.

Question 16

What neurotransmitters are CATECHOLAMINES?

Answer 16

1) DOPAMINE
2) NOREPINEPHRINE
3) EPINEPHRINE

Question 17

What are the uses Dopamine?

Answer 17

• Dopamine is involved in regulation of motor activity, motivation and reward, mood, sleep, learning, attention, etc.
• Parkinson’s disease is related to the death of dopaminergic neurons in the substancia nigra (part of the subthalamus).
• Reduced levels of dopamine may be related to attention deficit hyperactivity disorder (ADHD).
• Too much dopamine may be related to schizophrenia.

Question 18

What are the uses of Norepinephrine?

Answer 18

Norepinephrine is involved in alertness, focus, positive feelings of reward.

Question 19

What are the uses of epinephrine ?

Answer 19

Epinephrine (also referred to as adrenalin) is involved in alertness and, together with NE, is part of the “fight-or-flight” stress response.

Question 20

How are catecholamines made?

Answer 20

-catecholamines are derived from the amino acid tyrosine by a series of enzymatic steps that convert tyrosine into dopamine, then into norepinephrine, then into epinephrine.

Question 21

How are catecholamines eliminated?

Answer 21

eliminated from the synaptic cleft by either

1) reuptake transporters or
2) by degradation enzymes (like monoamine oxidase [MAO] or catechol-O-metyltransferase [COMT]).

Question 22

What drugs disrupt reuptake transporters in catecholamines ?

Answer 22

1) cocaine

2) amphetamines

Question 23

What are used as antidepressants?

Answer 23

MAO inhibitors

Question 24

What are SEROTONIN?

Answer 24

- Regulates aggression, emotional processing, mood, sleep, sexuality, appetite and metabolism. - Increases in levels of serotonin are related to obsessive-compulsive disorder and schizophrenia. - Decreases in levels of serotonin are related to depression.

Question 25

How is SEROTONIN made?

Answer 25

- made from the amino acid tryptophan in two enzymatic steps. - Because tryptophan is an essential amino acid, it must be obtained from the diet and transported to neurons for use in serotonin biosynthesis

Question 26

How is serotonin eliminated?

Answer 26

It is eliminated by : 1) reuptake transporters or 2) by degradation enzymes (like monoamine oxidase [MAO

Question 27

What drugs disrupt serotonin reuptake transporters ?

Answer 27

cocaine and amphetamines

Question 28

What drug is a “selective serotonin reuptake inhibitor” (SSRI) that can be used instead of a non-selective MAO inhibitor?

Answer 28

Prozac (specific to serotonin)

Question 29

What are GLUTAMATE AND GABA?

Answer 29

- Glutamate is the major excitatory neurotransmitter in the brain whereas GABA is the major inhibitory neurotransmitter in the brain. - Together, glutamate and GABA maintain the balance between excitation and inhibition in the brain. - Defects in either pathway can lead to epilepsy and seizures.

Question 30

How are Glutamates and GABA different from ACh, catecholamines and serotonin?

Answer 30

The neurotransmitters mentioned so far (ACh, catecholamines and serotonin) are made in a small subset of neurons by specific biochemical pathways. In contrast, glutamate and GABA are made in most neurons and are also universal cellular constituents.

Question 31

How are glutamate and GABA made?

Answer 31

- Glutamate is made from the amino acid glutamine by the enzyme glutaminase; it can also be derived as a byproduct of the Krebs cycle. - GABA is synthesized from glutamate by the enzyme glutamic acid decarboxylase (GAD).

Question 32

How are glutamate and GABA eliminated?

Answer 32

glutamate and GABA are eliminated from the synaptic cleft by either reuptake transporters or by degradation enzymes (GABA- transaminase) in neurons or glia.

Question 33

What drugs are agonists of the GABA receptor?

Answer 33

1) barbiturates 2) benzodiazepines 3) alcohol (ethanol)

Question 34

What are OPIOIDS?

Answer 34

- Opioid type of peptide neurotransmitters are made of small chains of amino acids (polypeptides) derived from cleavage of larger precursor proteins made in the nucleus of appropriate neurons - neurotransmitters are involved in pain perception and reward mechanisms.

Question 35

What are endorphins and enkephalins?

Answer 35

- Endorphins are chains of 16 to 30 amino acids of specific sequence. - Enkephalins have shorter chains (about 5 amino acids).

Question 36

What are natural opiates made from the opium poppy?

Answer 36

1) morphine | 2) codeine

Question 37

What drugs are agonists of endogenous opioid receptors?

Answer 37

1) morphine (natural) 2) codeine (natural) 3) heroin (synthetic, man-made) 4) oxycodone (synthetic, man-made)

Question 38

How are they stopped/ eliminated?

Answer 38

Signals are terminated by specific peptidases.