Term
| Presynaptic Regulation of Serotonin Transmission |
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Definition
- Tryptophan transport by Na+ symporter
- Tryptophan is converted to 5-hydroxytryptophan by tryptophan hydroxlyase (rate-limiting step)
- 5-hydroxytryptophan is converted to 5-HT by AADC
- 5-HT is concentrated into vesicles by a H+ antiporter (VMAT)
- Action potential opens Ca2+ channels, [Ca2+]i increases and vesicles move to axonal membrane
- 5-HT is released and binds to postsynaptic 5-HT receptors and presynaptic 5-HT1D receptors (negative feedback)
- 5-HT can be recycled back into presynaptic terminal via 5-HT/Na+ symporter where it can be repackaged into vesicles or degraded via MAO
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Term
| Presynaptic Regulation of Norepinephrine Transmission |
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Definition
Almost identical to DA Transmission except:
- When DA enters vesicles, it is converted to NE
- NE is released from cell (after depolarization) and binds to postsynpatic NE receptors or presynaptic alpha2 receptors (negative feedback)
- NE can reenter presynaptic terminal via NE/Na+ symporter where it is repackaged into vesicles or degraded via MAO
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Term
| NE Negative Feedback Mechanism |
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Definition
| When NE binds to presynaptic alpha2 receptors (autoreceptors), it results in decreased NE release and decreased NE synthesis through down-regulation of the tyrosine hydroxylase enzyme |
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Term
| 5-HT Negative Feedback Mechanism |
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Definition
| When 5-HT binds to presynaptic 5-HT1D receptors (autoreceptors), it results in decreased 5-HT release and decreased 5-HT synthesis through down-regulation of the tryptophan hydroxylase enzyme |
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Term
| Activation of signal transduction pathways by NE and 5-HT offers what benefits to different areas of the brain? |
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Definition
| They "turn off" detrimental gene expression and "turns on" beneficial gene expression which favors neurogenesis thus restoring neuron loss in the hippocampus, prefrontal cortex, and amygdala --> alleviation of symptoms |
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Term
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Definition
- Amitriptyline
- Clomipramine
- Doxepin
- Imipramine
- Trimipramine
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Term
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Definition
- Desipramine
- Nortriptyline
- Protriptyline
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Term
| "Flip" Model for Monoamine Transporters |
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Definition
- Transporter "flips" through the membrane (extracellular face of the tranporter "flips" to the intracellular face) thereby moving NT and sodium into the cell
- After NT is released the transporter "flips" back
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Term
| MOA of TCAs: Immediate Action and Delayed Action |
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Definition
Immediate
Inhibits NE and 5-HT uptake
Delayed
- Decreased presynaptic receptors (alpha2 and 5-HT1D) which results in decreased negative feedback
- As a result, more NE and 5-HT are released into the synaptic cleft
- Increased transcription of beneficial genes in turn promoting neurogenesis and decreasing apoptosis
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Term
| TCAs - Tertiary Amines: Selectivity |
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Definition
| Mixed or slight selectivity for 5-HT reuptake inhibition |
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Term
| TCAs - Secondary Amines: Selectivity |
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Definition
| Selective for NE reuptake inhibition |
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Term
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Definition
Related to H1, alpha1, M1, and Na+ channel antagonism
- Dry mouth, constipation, urinary retention, blurred vision
- Orthostatic hypotension
- Sedation
- Cardiotoxicity especially with overdose (QT interval, QRS complex)
- Seizures
- Weight gain
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Term
| Serotonin-Norepinephrine Reuptake Inhibitors |
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Definition
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Term
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Definition
- Citalopram
- Fluoxetine
- Fluvoxamine
- Paroxetine
- Sertraline
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Term
| MOA of SSRIs: Immediate Action and Delayed Action |
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Definition
Immediate
Inhibits 5-HT uptake
Delayed
- Decreased presynaptic receptors (5-HT1D) which results in decreased negative feedback
- As a result, more 5-HT is released into the synaptic cleft
- Increased transcription of beneficial genes in turn promoting neurogenesis and decreasing apoptosis
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Term
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Definition
- Fewer ADRs than TCAs
- Nausea most common (5-HT3,4 in GI)
- Sexual dysfunction (decreased libido, impaired orgasm)
- Suicidal ideation
- Serotonin Syndrome (concurrent MAOI use)
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Term
| Serotonin Syndrome Signs/Symptoms |
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Definition
- Onset within hours
- Tremor
- Hyperthermia
- HTN
- Coma
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Term
| Norepinephrine-Selective Reuptake Inhibitors |
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Definition
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Term
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Definition
- Norepinephrine Selective Reuptake Inhibitors
- Weak affinity for H1, M1, and alpha1 receptors
- Better side effect profile than TCAs
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Term
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Definition
Norepinephrine Selective Reuptake Inhibitor
Minor 5-HT reuptake inhibition
ADRs
- Lowers seizure threshold
- Anti-ACh
- Sedation
- Hypotension
- Cardiac conduction effects similar to TCAs
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Term
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Definition
- Phenelzine
- Tranylcypromine
- Isocarboxazid
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Term
| Selective MAO-A Inhibitors |
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Definition
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Term
| Selective MAO-B Inhibitors |
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Definition
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Term
| Substrate Specificity for MAO-A |
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Definition
- Epinephrine
- Norepinephrine
- 5-HT
- Tyramine
- Dopamine
MAO-A is a target for drugs useful in treating depression |
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Term
| Substrate Specificity for MAO-B |
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Definition
- Tyramine
- Dopamine
- Phenylethylamine
- Benzylamine
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Term
| NE is converted to ________ via MAO |
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Definition
| Dihydroxyphenylglycoaldehyde (DOPGAL) |
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Term
| 5-HT is converted to ________ via MAO |
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Definition
| 5-hydroxyindole acetaldehyde |
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Term
| Bupropion: MOA, Metabolism, ADR |
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Definition
Weak NE and 5-HT reuptake inhibition
Active metabolites -- inhibit DA reuptake (amphetamine related metabolites)
Increased seizure risk |
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Term
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Definition
- Antagonist of presynaptic 5-HT1D and Alpha2 autoreceptors
- Results in increased [5-HT] and [NE] in the synaptic cleft
Strong H1 antagonist (sedation) |
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Term
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Definition
May block presynaptic receptors
Partial postsynaptic agonist
ADR
- risk of hepatic failure
- hypotension (alpha1 antagonism) --> reflex tachycardia
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Term
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Definition
May block presynaptic receptors
Partial postsynaptic agonist
ADR
- sedation
- hypotension (alpha1 antagonism) --> reflex tachycardia
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