Mixed Serotonergic Agents Flashcards
(18 cards)
Trazodone
Serotonin-2 receptor agonist + serotonin blocking/re-uptake effects
5-HT2 and 5HT reuptake inhibitors
Also blocks alpha1 receptors –> dizziness and hypotension
Most often used for insomnia
SE: hypotension, dizziness, sedation, priapism
Norepinephrine-Dopamine Reuptake Inhibitor (NDRI)
Bupropion: unclear mechanism of action. Has weak DAT-I and NET-I: pharmacologic actions appear more potent than weak properties
- has lead to proposal that it acts vaguely as an adrenergic modulator
Metabolized to a number of active metabolites: so a pre-cursor drug in some ways.
DAT considerations
Occupancy of DA is like ‘goldilocks’ if you have too much too quick leads to euphoria/reinforcement (cocaine), slower occupancy makes things like Bupropion less abusable.
Bupropion
It is generally activating/stimulating without sex SE.
Targets ‘DA deficiency syndromes’ - ie decreased positive affect, improves sx of long-term SSRI/SNRI such as loss of happiness/joy, interest, increases enthusiasm, energy and self confidence.
Novel NDRI tx
Bupropion + dextromethorphan (NDMA antagonist) in late stage trials for depression and Alzheimer’s agitation
Agomelatine
Approved outside US: stimulates Melatonin receptors and blocks 5HT2c receptors to re-synchronize circadian rhythm
Mirtazapine
Approved for unipolar depression. Doesn’t block any monoamine transporters, works by 5 different mechanisms
Mirtazapine: mechanism 1
H1 Antagonist - causes sedation and weight gain
Mirtazapine: mechanism 2
5HT2A antagonist - increases downstream release of DA in prefrontal cortex (assoc w/ AD actions) and improves sleep (slow wave)
Mirtazapine: mechanism 3
5HT2C antagonist - increases release of NE and DA in prefrontal cortex
Mirtazapine: mechanism 4
Alpha2 antagonist - enhances release of NTs; stops E from turning ‘off’ its own release.
Interacts with pre-synaptic alpha2 ARs so stop negative feedback of both NE and similarly SER: ‘they cut the SER break cables’
Have dual effect like SNI
Combo Mirtazipine and SNRI = California Rocket Fuel
Mirtazapine: mechanism 5
5HT3 antagonist: this is best known chemo-receptor in GI tract (n/v) but in brain this regulates downstream NT release.
5HT3 usually localized on GABA interneurons (excitatory)
- When serotonin stims 5HT3 receptor this causes GABA to inhibit downstream neurons
- Antagonizing 5HT3 stops disinhibition of glutamate release and all downstream effects
Mirtazapine SE
Somnolence, wt gain, dry mouth, constipation (anticholinergic)
Vortioxetine
Newer agent, acts as SSRI, and antagonist/agonist at various 5HT receptors. This blend causes downstream release of many NTs.
Has good AD and pro-cognitive actions (increases processing speed)
Vortioxetine SE
diarrhea, ejaculatory dysfunction, anorgasmia, nausea
Metabolized by CYP2D6, so poor metabolizers –>toxicity
NMDA receptor antagonists
Ketamine: fringe: regulates glutamine activity by blocking NMDA receptors.
Used at sub-anesthetic levels, given IV can lead to rapid improvement in depressive sx and sometimes anti-SI effects
Only lasts a few days, can enhance monoamine AD tx
Causes immediate improvement in neuroplasticity (neurotrophic hypotheses to depression)
Esketamine
Is the S enantiomer of Ketamine: intranasal form
Initial 2 week starting dose, then decrease to once weekly or bi-weekly for augmentation of standard Tx - up to 1 yr
St John’s Wort
Effective in mild depression
Many active compounds: has MAOI action, some re-uptake inhibition of MAO’s
SE: dry mouth, dizziness, confusion
CYP3AF and p-glycoprotein inducer so can decrease Rx levels and can cause serotonin toxicity when mixed with other AD’s
