Intro To CNS Flashcards
Describe the small molecules neurotransmitters.
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)
What are two major classes of neurotransmitters?
1) small molecules
2) peptides
What are the small molecule neurotransmitters?
1) acetylcholine (ACh)
2) dopamine (DA)
3) norepinephrine (NE)
4) epinephrine
5) serotonin (5HT)
6) glutamate
7) GABA
Describe peptide neurotransmitters.
- These are also “small” molecules, these are typically larger than the ‘small molecules’.
- There is an incredible diversity of peptide neurotransmitters in the brain.
What classes are included in the peptide neurotransmitters?
1) opioid-type peptides (like endorphins and enkephalins)
2) gut-brain peptides (like substance P)
3) hypothalamic-releasing hormones
4) the pituitary hormones
What is ACETYLCHOLINE?
- 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.
How is Alzheimer’s disease related to ACh?
Alzheimer’s disease is related to the death of cholinergic (ACh-containing) neurons in the cortex.
What are the two types of ACh receptors?
- 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
What is ACh made of?
- 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.
How is ACh eliminated?
ACh is eliminated by the enzyme acetylcholinesterase (AChE) that breaks down the neurotransmitter into choline and acetate.
ACh: What is an organophosphate-containing insecticides drug?
Malathion
ACh: What drug are nerve gases that are irreversible AChE inhibitors?
Sarin
What are used for Alzheimer’s symptoms?
Reversible AChE inhibitors
What is ACh receptor agonist?
Nicotine
What is a ACh receptor antagonist?
scopolamine
What are CATECHOLAMINES?
Catecholamines are a family of neurotransmitters that contain a “catechol” nucleus.
What neurotransmitters are CATECHOLAMINES?
1) DOPAMINE
2) NOREPINEPHRINE
3) EPINEPHRINE
What are the uses Dopamine?
- 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.
What are the uses of Norepinephrine?
Norepinephrine is involved in alertness, focus, positive feelings of reward.
What are the uses of epinephrine ?
Epinephrine (also referred to as adrenalin) is involved in alertness and, together with NE, is part of the “fight-or-flight” stress response.
How are catecholamines made?
-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.
How are catecholamines eliminated?
eliminated from the synaptic cleft by either
1) reuptake transporters or
2) by degradation enzymes (like monoamine oxidase [MAO] or catechol-O-metyltransferase [COMT]).
What drugs disrupt reuptake transporters in catecholamines ?
1) cocaine
2) amphetamines
What are used as antidepressants?
MAO inhibitors
What are SEROTONIN?
- 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.
How is SEROTONIN made?
- 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
How is serotonin eliminated?
It is eliminated by : 1) reuptake transporters or 2) by degradation enzymes (like monoamine oxidase [MAO
What drugs disrupt serotonin reuptake transporters ?
cocaine and amphetamines
What drug is a “selective serotonin reuptake inhibitor” (SSRI) that can be used instead of a non-selective MAO inhibitor?
Prozac (specific to serotonin)
What are GLUTAMATE AND GABA?
- 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.
How are Glutamates and GABA different from ACh, catecholamines and serotonin?
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.
How are glutamate and GABA made?
- 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).
How are glutamate and GABA eliminated?
glutamate and GABA are eliminated from the synaptic cleft by either reuptake transporters or by degradation enzymes (GABA- transaminase) in neurons or glia.
What drugs are agonists of the GABA receptor?
1) barbiturates
2) benzodiazepines
3) alcohol (ethanol)
What are OPIOIDS?
- 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.
What are endorphins and enkephalins?
- Endorphins are chains of 16 to 30 amino acids of specific sequence.
- Enkephalins have shorter chains (about 5 amino acids).
What are natural opiates made from the opium poppy?
1) morphine
2) codeine
What drugs are agonists of endogenous opioid receptors?
1) morphine (natural)
2) codeine (natural)
3) heroin (synthetic, man-made)
4) oxycodone (synthetic, man-made)
How are they stopped/ eliminated?
Signals are terminated by specific peptidases.
