Lesson 7: Drugs Flashcards
Which two neurotransmitters do 99% of nerons release?
Glutamate and GABA
What are the characteristics of glutamate?
It encourages spiking (excitatory sodium ions) and membrane depolarization
- agonists: seizures and excitotoxicity
- antagonists: dissociative anaethetics
What are the characteristics of GABA?
It encourages less spiking (inhibitory: chloride ions) to occur, and membrane hyperpolarization
- antagonists: seizures
- agonists: anaethetics, anticonvulsants, muscle relaxants, sleeping pills, etc.
What are the four classic neurotransmitters (that we call neuromodulators)?
Acetylcholine, dopamine, serotonin, and norepinephrine
Why do we call acetylcholine, dopamine, serotonin, and norepinephrine neuromodulators?
Because they are not released from every neuron in the brain
- they act on metabotropic receptors (NOT ionotropic receptors)
- they don’t produce simple excitatory or inhibitory effects in the CNS
- they can diffuse short distances outside of the synapse and influence the activity of neighboring neurons
What is the synonym of norepinephrine?
Noradrenaline
What is the synonym of epinephine?
Adrenaline
What are the conventional neurotransmitters and their characteristics?
Glutamate, GABA, dopamine, serotonin, acetylcholine, and norepinephrine
- made locally in axon terminals
- packaged in small synaptic vesicles
- only these can activate ionotropic receptors (and metabotropic receptors)
- recycled and reused
- heavily regulated
What are neuropeptides and their characteristics?
They are strings of amino acids (10-30x bigger than the classical neurotransmitters)
- NOT made locally: made in the cell body
- packaged in large dense core vesicle
- ONLY activate metabotropic receptors (NOT ionotropic receptors)
- NO RECYCLING of neuropeptides
- may diffuse long distances
What are lipid-based signaling molecules?
They are synthesized and released on demand: post-synaptic neuron makes the decision (sends feedback) to the pre-synaptic neuron
- only activate metabotropic receptors
What are the monoamine neuromodulators?
Serotonin, dopamine, norepinephrine, and epinephrine
What is the name of the only protein that packages the monoamine neuromodulators into synaptic vesicles?
The vesicular monoamine transporter (VMAT)
Which monoamines are catecholamines? Which are indolamines?
Catecholamines: dopamine, norepinephrine, epinephrine
Indolamines: serotonin
What does acetylcholine cause when introduced in excessive amounts in our system?
Acetylcholine causes muscle contractions (such as paralysis)
What neurotransmitter do motor neurons generally release?
Acetylcholine
What neurotransmitter do sensory neurons generally release?
Glutamate
How does venom enter our cells?
Venom sneaks in by attaching to the membrane and then goes into the cell
- Black Widow Spider venom will act like a calcium ion - doesn’t need any action potential to open the vesicle, so acetylcholine will continuously be released
What is neostigmine?
A drug that inhibits the activity of acetylcholinesterase, which is the enzyme that breaks down acetylcholine in the synaptic cleft
- it causes acetylcholine to stay around longer in synapses, causing more muscle contraction
What is an agonist receptor?
A drug that directly or indirectly increases the activity of postsynaptic receptor proteins
What is an antagonist receptor?
A drug that directly or indirectly decreases the activity of postsynaptic receptor proteins
How do direct agonists/antagonists affect postsynaptic receptor activity?
They directly bind to postsynaptic receptors
How do indirect agonist/antagonist affect postsynaptic receptor activity?
The proteins they bind to are not postsynaptic receptors
- they bind to other proteins
What are antipsychotics?
A class of drugs used to treat psychosis
- they bind to more than one type of receptor, but one action they all have in common is they directly block the dopamine D2 receptor, which is an inhibitory metabotropic receptor expressed by neurons all over the brain
WHat is the difference between the drugs that cause hallucinations and those that do not?
Those that do: activation of the g protein ‘Gi/o’ which results in hallucinations
What is biased agonism?
When a metabotropic receptor ligand causes the receptor to preferentially activate one type of intracellular g protein, whereas another ligand at the same receptor might preferentially activate a different g protein
What is a competitive agonist?
It activates the receptor by binding where the neurotransmitter normally binds
- partial competitive agonist: less postsynaptic receptor activity than we normally would (similar to full antagonist)
What is a competitive antagonist?
It attaches to the same binding where the neurotransmitter normally binds, but it doesn’t activate the receptor
- competitive antagonists are full antagonists
What is affinity when talking about a binding site?
Affinity refers to the probability and tightness of ligand-receptor binding
What is a non-competitive agonist?
Fully or partially activates the receptor
What is non-competitive binding?
When a drug binds to a receptor at a site that does not interfere with the binding site of the principal ligand
- it is possible for a neurotransmitter to bind on one site of a receptor while a drug binds on another
What is a non-competitive antagonist?
It fully blocks receptor activation.
- it doesn’t compete for the neurotransmitter binding site
What are allosteric modulators?
Non-competitive drugs that only influence receptor activity when the neurotransmitter is also bound to the receptor
- negative: less neurotransmitters can come in (inhibitory)
- positive: amplify neurotransmitters that come in (excitatory)
How are classical neurotransmitters made?
They are mad ein axon terminals from precursor molecules (generally amino acids)
- the synthesis of neurotransmitter from precursor molecules is controlled by enzymes
- once made, neurotransmitters are packaged into synaptic vesicles
What controls the clearance of neurotransmitters from the synapse?
By reuptake transporter proteins and enzymatic deactivation
What are drugs that block the reuptake of catecholamine neurotransmitters and transporters?
Methylphenidate, cocaine, adderall, and crystal meth
