Card Set Information
All cell bodies/Soma for serotonergic neurons are in the:
Hindbrain region: pons and medulla in a series of nuclei along the midline called the Raphe nuclei
Serotonergic neurons Enter what brain parts:
Midbrain, limbic structures (hypothalamus and hippocampus), cerebral cortex (cortical and subcortical innervations)
down the spinal chord = regulate information processing and pain perception
5HT3 receptor is what type of receptor
Ligand gated ion channel = excitatory receptor expressed in the brain
All seratonin receptors except 5HT3 are what type?
“off” switch for serotonin transmission:
Pre-synaptic seratonin receptor, local negative feedback:
5HT1a autoreceptor and b
SSRIs target SERT of 5HT1A or B?
5HT1A or B
What can MAOIs treat?
Treat depression, OCD, ADHD, and to control appetite
Amphetamine stimulates serotonin release be what action?
Depends on it binding to and being transported by the reuptake pump
Seratonin reuptake pump is the target for what drugs?
TCAsa nd SSRIs
Differences between the TCAs and SSRI.:
SSRIs = relatively selective for the serotonin transporter, safer
TCAs = block both serotonin and NE transporters
SImilrities between the TCAs and SSRI.:
MOAI - Blocked the reuptake of biogenic amines
Why respirine taken off the market?
HTN treatment - caused profound depression/suicide b/c deleted biogenic amines
Why is biogenic amine theory not correct?
1. Some antidepressants don’t block reuptake of biogenic amines and they’re not MAOI
2. biogenic amines elevated in the synaptic cleft 30 minutes after you take one
Supersensitivity of receptors in the brain leads to depression?
chronic antidepressant treatment affects what receptors?
HHT, alpha 1 adrenergic and B-adrenergic
Action of 5HT1A:
hyperpolarizes the membrane
Action of SSRIs after first dose on neural firing:
increases 5-HT1A and decreases rate of firing
Action of SSRIs after chronic dose on neural firing:
: raphe 5-HT neuron activity
downregulation of 5-HT1A receptors
elevate serotonergic transmission - unimpeded
Cell bodies for NE neurons in the brain are in the:
BRAIN STEM’S Locus Ceruleus - blue body
NE neurons send their projections:
In the descending manner to the spinal cord
Ascending manner to the forebrain structures (limbic
: hypothalamus and hippocampus) and cerebral cortex
Post-synaptic noradrenergic receptors:
Alpha adrenergic or beta adrenergic receptors
Pre-synaptic noradrenergic receptors:
Alpha-2 adrenergic receptor
DA cell bodies are located:
Midbrain: VTA or Substantia nigra
Substantia nigra to the striatum = Parkinson’s disease
Mesolimbic dopamine pathway
VTA to limbic structures = nucleus accumbens and the amygdala (reward circuitry pathway)
Meso-Cortical dopamine pathway
VTA to the cerebral cortex = Regulates/contributes to thoughts = target for antipsychotic drugs
Dopamine cell bodies Project to:
Limbic structures as well as the cerebral cortex
5 different post-synapatic dopamine receptor subtypes, what type of receptor are they:
All G-protein coupled receptors
VTA and Substantia nigra dopamine cell bodies = what are the somato-dendritic auto-receptors - inhibit the firing rate?
D2 dopamine receptors - coupled to K+ channels
Opioids bind mu opiod receptors on:
GABAergic interneurons in the VTA
Leads to Release dopamine in the nucleus accumbens = rewarding or pleasurable experience
Psychostimulant like cocaine or an amphetamine affects what receptors?
Inhibits the dopamine transporter, DAT
Cholinergic pathway that goes to the hippocampus = very important for:
Block muscarinic receptors at hippocampus = difficulty with:
Where are Ach neuron cell bodies located and where do they proect to?
BMSI nucleus sends cholinergic projections to the cerebral cortex- Alzheimer’s
(True/False) Muscarinic and nicotinic cholinergic receptors are important for brain function.
True – mediate reward of nicotine
Desipramine has a little bit of selectivity for :
NE over serotonin
Metabolite of imipramine is:
Desipramine = both are biologically active TCAs.
Mechanism of action of TCAs:
inhibit the reuptake of NE and serotonin
TCAs can produce sedation, related to their:
alpha-1 adrenergic receptor affinity
TCA cardiac toxicity is related to what feature?
Ion channel blockade
TCA adverse effect: Atropine-like side effects: dry mouth, constipation, blurred vision, mydriasis, metallic taste, urine retention is related to what receptors?
TCA adverse effect: Orthostatic hypotension is related to what receptors?
a1-AR and possibly a2-AR blockade.
TCA adverse effect: Drowsiness, sedation and weight gain is related to what receptors?
Alternate receptor interaction of TCAs, put in order of most to least:
Amitrylptyline >Doxepin> Imipramine = Clomipramine
SSRI most potent in blocking SERT:
Paroxetine (does not equate to efficacy)
SSRI most selective for the SERT vs NET
Escitalopram (does not equate to efficacy)
SSRI most potent against DAT:
(Not a high affinity blocker of DAT, but amongst the SSRIs, it has the highest affinity)
SSRI most potent anticholinergic agent:
Potential Clinical Consequences of 5-HT Reuptake Blockade:
Impaired cognition (No more likely to impair cognition than a TCA)
SSRI with highest rates of sexual dysfunction:
SSRI with worst side effects:
When there is non-compliance due to adverse effect, is it reasonable to switch to one SSRI to another?
SSRI with a flat-dose response curve:
Escitalopram (Lexapro) Potency of blocking 5-HT is comparable to:
SSRI NOT metabolized by CYP 3A4:
SSRIs from activating to sedating:
Proxac – Zoloft – Escitalopram – Fuvoxamine – Paxil
MOA Mirtazapine :
ALPHA 2 ANTAGONIST:
Doesn’t block serotonin or NE transport = increases vesicular release =Potentiation of NE transmission in the CNS
BOTH BLOCK THE NEGATIVE FEEDBACK LOOP
= congener of trazodone
Same kind of profile as trazadone = some 5-HT2 blocking activity = ability to block serotonin transport = some ability to block norepinephrine transport
BOTH BLOCK THE NEGATIVE FEEDBACK LOOP
Why does Tyramine cause negative effects:
promotes the release of NE in the periphery
Causes MABP surge in periphery
Do MOAs produce adaptive changes in CNS similar to TCAs and SSRIs?
Irreversible inhibitors of MAO-A and MAO-B:
(isocarboxazid and Phenelzine)
reversible inhibitors of MAO-A and MAO-B:
BP effect of MOAIs:
May lower, not profound
glutamate receptor antagonist
N-methyl-D-Aspartate (NMDA) subtype of glutamate receptor
Couple of hours = improvement in mood
SJW effects what receptor types?
DA, 5HT, NE, GABA, Glutamte – all with low potency
Molecular mechanism of action of HYPERFORIN:
REDUCE THE SODIUM GRADIENT
-not competitive inhibitor
Hyperforin or hypericin cross the BB well?
GI distrubance = very high with fluoxetine, BUT almost non-existant in:
St. John’s Wort
Adverse effects of SJW:
MOA of Lithium:
alter the coupling of receptors with G-proteins.
Inhibits breakdown of IP2 to IP1
depletion of DAG and IP3 and ¯ [Ca2+]
- not really selective
Activates phospholipase C
disrupts glycogen synthase/adenylyl cyclase activity