Midterm 1 - Psychopharmacology Flashcards
3 Things That Can Happen to a NT When It’s Released
- Diffuse Away
- Broken down with enzymes
- Re-Uptake
MAOs (A&B)
(Enzyme Deactivation)
Enzyme that destroys excess amounts of NT by inactivating it.
Not only do MAOs break apart NTs, they re-package them so they are ready to go to the synaptic cleft and be released again.
Ex. MAOb breaks down excess dopamine. Deprenyl is a dopamine agonist because it destroys MAOb (which breaks it down in the first place).
SNAP-25
A protein that, when activated by Ca2+, drags the vesicle to the appropriate docking location on the pre-synaptic membrane.
Pinocytosis
Reuptake (the process of the membrane pinching off and becomming a re-packaged vesicle).
Exocytosis
Release
2 Main Drug Classifications
- Agonist
- Antagonist
Agonist
A drug that increases the action of the synapse/NT.
3 Ways A Drug Can Be An Agonist
- It can mimic the NT.
- It can promote release of the NT.
- It can block re-uptake of the NT.
Amphetamine
Dopamine agonist (mimics dopamine).
SSRI
BLOCKS RE-UPTAKE
E.g., Prozac
Developed because other antidepressants on the market would block re-uptake of serotonin AND norepinephrine. But nor-epinephrine blockers are good for lethargic depressed people, but not anxious depressed. Therefore, SSRIs do away with the norepi component.
Antagonist
A drug that decreases the function of the NT at the synapse.
How Does an Antagonist Work?
BLOCKS the post-synaptic receptors (therefore NT can’t bind to the receptor and open the ion channel).
Anti-Psychotics
Dopamine antagonists.
3 Classes of NTs
- Quaternary Amine
- Monoamines
- Amino acids
Acetylcholine (ACh)
Quaternary Amine
Movement workhorse.
Main NT of the muscular system. Operates at neuromuscular junction.
2 Categories Monoamines
- Catecholeamines
- Indoleamines
Catecholeamines
(3)
Dopamine
Norepinephrine
Epinephrine
Indoleamines
Serotonin
Melatonin
Catecholeamine Synthesis Pathway
Mediated by enzymes.
- L-Tyrosine
- L-Dopamine
- Dopamine
- Norepinephrine
- Epinephrine
Indoleamine Synthesis Pathway
- L-Tryptophan
- 5-Hydroxytryptophan
- 5-Hydroxytryptamine (5-HT) *Serotonin
- Melatonin
Factories in the Midbrain That Make NTs
- Substantia Nigra - dopamine (nigrostriatal pathway)
- Raphe Nuclei - 5-HT
- Ventral Tegmental Area - dopamine (median forebrain bundle)
- Locus Ceruleus - Norepinephrine
Nigrostriatal Pathway
Dopamine pathway that starts in the substantia nigra and ends in the striatum (starts and stops movement).
Parkinson’s
Median Forebrain Bundle (MFB)
Dopamine pathway that starts in the midbrain (VTA) and goes to the forebrain (PFC).
***Thoughts and emotions. Thought disorders.
***Schizophrenia and bipolar (mania = too much dopamine).
Without dopamine in PFC, you lose executive functioning.
Norepinephrine
- Locus Ceruleus
- Level of game
- Over-productivity = anxiety
- Role in controlling brain wave functions when you sleep (wake up when norepi is released).
- Will increase when in danger
Raphe Nuclei
Makes 5-HT which goes just about everywhere.
Tectum
Roof of midbrain.
Tegmentum
Floor of midbrain.
Amino Acid NTs
(3)
Most prevalent NTs in the brain! A majority of brain function is conducted from the release of glutamate and GABA.
- Glutamate
- GABA
- Glycine
Glutamate
AA NT
- Always excitatory
- Primary NT in the brain!
GABA
AA NT
- Always inhibitory
Glycine
AA NT
- Inhibitory
Dopamine Agonist
Stimulant
- Meth = Mimics dopamine
- Cocaine = Selective Dopamine Re-Uptake Inhibitor
Dopamine Antagonist
Opposite of a stimulant
- Anti-psychotic (Thorazine, Haldol, Chlorpromazine)
- Interrupts transmission to median forebrain bundle
- Problem = Movement disorders (dopamine initiates movement). Parkinsonian like symptoms.
5-HT Agonist
- Increases serotonin
- Increases mood, decreases appetite, makes sleepy, gives hallucinations
- Hallucinogens
5-HT Antagonist
Depressant.
Experimental only (may block hallucinations)
GABA Agonist
Increases inhibition.
- Barbituates
- Benzos - works on GABAa and will compete with alcohol (mimic GABA and let Cl- in) (creates IPSP)
- Alcohol - works on GABAa and will compete with benzos
Inhibitory NTs let in negatively charged ions.
GABA Antagonist
Excitatory
No known GABA antagonists.
Glutamate Agonist
Stimulant
- No known drugs that act as GA.
Glutamate Antagonist
- Anesthetics (put to sleep but doesn’t paralyze)
- E.g., propophol
ACh Agonist
- Increased motor function and firing at neuromuscular junction.
- Overexcites heart muscles.
- Spider and snake venom
- POISON
ACh Antagonist
- Paralyzes
- Muscles get too relaxed and stop working
- Botulism
L-DOPA
Parkinson’s drug that increases synthesis of dopamine in the nigrostriatal pathway.
Dopamine Receptors
- Branch 1 = D1, D2, D3
- Branch 2 = D4-D5
Dopamine D2 Receptor
- Key movement receptor in striatum
- D2 Antagonist blocks motor function
D4 Dopamine Receptor
- Found in forebrain
- D4 Antagonist blocks hallucinations without blocking movement.
5-HT Receptors
1-17
5-HT 3,4 Receptors
Satiety
5-HT 2a
Responsible for hallucinations. Active site for hallucinogens.
LSD, MDMA act on these receptors
MDMA
Promotes release of dopamine and can mimic dopamine.
Can also increase the release of 5-HT.
Therefore, it’s a combination dopamine and 5-HT agonist.
*Breaks down to meth in brain.
Most Common Receptors in the Brain
G-Protein coupled receptors
G-Protein Coupled Receptor
- Transmembrane
- NT will bind and activate G-Protein on bottom, inside cell receptor.
- This part that’s inside can send signals to other channels to open.
- Amplifies signal.
Hormones vs. NTs
Hormones
- Large
- Can go a long distance
NTs
- Small
- Only travel across synapses
***Both can alter behavior!
Endogenous Opioids
Endorphins, Enkaphalines
How do synapses maintain homeostasis?
Up-regulating and down-regulating post-synaptic receptor sites.
Down-Regulation vs. Up-Regulation
Down-Regulation
- Tolerance b/c receptors go down beneath surface so NTs/Drugs can’t find receptors (therefore have to take more and more = tolerance)
Up-Regulation
- Response to withdrawal
Tolerance
Neuron will get over-excited and compensate by down-regulating
(e.g., In meth, there’s way more release of dopamine)
Withdrawal
When stop taking drug, receptors will up-regulate (peak head back out to look for NT in synaptic cleft).
Withdrawal lessens with up-regulation
