NEUROSCIENCE DRUGS Anti-Depressants
Drug
MOA
Imipramine
Amitriptylin
e
Clomiprami
ne
Desipramin
e*
Nortriptylin
e*
Protriptylin
e*
*-NA
selective
1. neurotransmitter
availability by blocking
process of reuptake of NE
&/ or 5- HT in presynaptic
neuron concentration
of neurotransmitters in
synaptic cleft
2. Most TCA affect 1 or
more types of
neurotransmitter
receptor muscarinic
Ach , histamine
3. Anti-muscarinic effects
of TCA responsible for
adverse effects
TRICYCLICS - TCAS
Drug
ADRs
Use/Info
Route: Oral
Strong PPB
Excreted in
urine
1. Anticholinergic
effects - blurred
vision, dilated
pupils, dry skin &
mouth,
Rx:
urinary retention,
Depression,
constipation,
Panic disorder confusion
GAD, Postesp. in elderly
traumatic
2. Autonomic
disorder
effects- postural
hypotension 20 to adrenergic blockade
reflex tachycardia
3. ECG changes
widening of QRS
complex; arrhythmias
4. weight gain
5. Sedation 20 to
histamine blockade
Other Notes
1. Toxicity Cholinergic
blockade, Cardiac
arrhythmias, Convulsions
2. Inactivation via
glucuronide
Conjugation
3. Metabolized in liver by 2
Routes: a) N
demethylation ---- 30
amines converted to 20
amines
(imipraminedesmethylimipr
amineamitriptyline
nortriptyline )
b)ring hydroxylation
4. Imipramine enuresis,
chronic pain , panic attacks ,
phobias
5. Clomipramine PME , OCD
6. Amitriptyline neuropathic
pain
Drug
Venlafaxine
Effexor
Duloxetine
Cymbalta
SEROTONIN & NOREPINEPHRINE REUPTAKE INHIBITORS (SNRIS)
MOA
Drug Use/Info
ADRs
1. Dual serotonin &
norepinephrine reuptake
inhibition
2. Weak reuptake inhibition
of dopamine
1. higher doses
risk of elevated
blood pressure
Other Notes
1. Enhancing both
serotonergic &
noradrenergic
Neurotransmission
simultaneously may
provide
greater efficacy in
depression
treatment
Selective Serotonin Reuptake Inhibitors - SSRIs
General Info
Drug
Antidepressant effects take about 2-3 weeks to be noticeable
Withdrawal syndrome nausea, dizziness, anxiety, tremor, palpitations- worse with paroxetine,
venlafaxine
Onset: 36-72 hrs, Duration: 3-7 days, Solution - taper schedule
Clinical Uses: Depression, OC disorder (fluvoxamine),Social anxiety disorder, PME, Panic
disorder, PTSD, Premenstrual dysphoric disorder( PMDD)
MOA
Drug
ADRs
Other Notes
Use/Info
Fluoxetine
(prototype)
1. inhibition of serotonin
reuptake without significant
effects on norepinephrine,
muscarinic, histaminic or adrenergic receptors
Fluvoxamin
e
1. CYP3A4 inhibitor may
levels of concurrently
administered substrates for
enzyme e.g. diltiazem
leading to hypotension
T1/2: 48-72hrs
Active
product:
Norfluoxetine
(T1/2: 180hrs)
1. Anorexia, nausea,
diarrhea, Nervousness
2. Insomnia,Dizziness
3. Sexual dysfxn
4. risk of suicide in
children & adolescents
5.Serotonin
syndrome:
hyperthermia, muscle
rigidity, changes in
mental
status,autonomic
instability (vital signs
change)
1. Fluoxetine &
paroxetine
potent inhibitors of
CYP2D6 isoenzyme
unpredictable
elevations of TCAs
2. Benztropine,
haloperidol,
codeine/oxycodone, class
1c antiarrhythmics, blockers, bupropion are
also CYP2D6 substrates
Atypical Antidepressants
Drug
Bupropion
MOA
1. Inhibits reuptake of
serotonin, NE & dopamine
(possibly inhibits reuptake of
DA more than NE)
2. Non-competitive nicotine
receptor antagonist ; at high
concentrations inhibits firing
of noradrenergic neurons in
Drug Use/Info
ADRs
1. seizure risk,
especially in
patients with h/o
seizure or head
trauma
Other Notes
1. Anti- smoking
effects: inhibition of the
reductions in levels of
dopamine & NE levels in
the CNS that occur in
nicotine withdrawal likely
to be important
Trazodone,
Nefazodone
Mirtazapine
the locus
coeruleus
1. Serotonin antagonist
reuptake inhibitor
3. Mainly antagonize 5-HT2
receptors
1. Antagonizes -2 receptors
2. Blocks 5-HT2A/C & 5-HT3
receptors
1. Histamine
Inhibition:
sedation,
fatigue, appetite,
weight gain
1. High affinity for
histamine postsynaptic
receptor
Monoamine oxidase inhibitors (MAOIs)
Clinical Uses
Drug
Phenelzine
Antidepressant- due to build up of amine levels in brain
Anti-parkinsonism specific MAO- B inhibitors result in dopamine levels.
MOA
1. Inhibit one or both forms
of brain MAO cytosolic
Drug Use/Info
ADRs
1. Orthostatic
hypotension
Other Notes
1. Rarely used because
of toxicity & potentially
Non selective:
Tranylcypromin
e
MAO A
inhibitor:
Moclobemide
MAO- B
inhibitor:
Selegiline
stores of NE & 5 HT in nerve
terminals
2. Inhibition of MAO- A
correlates with
antidepressant activity
3. MAOI prevent breakdown
of tyramine in guthigh
serum levelsenhance
peripheral effects of NE,
dramatically
b.p.
4. Patients who take MAOI &
ingest foods rich in tyramine
may experience
b.p ,
stroke, MI
2.
3.
4.
5.
6.
7.
8.
Impotence
Agitation
Hallucinations
Seizures
Hyperthermia
Hepatotoxicity
Hyper- reflexia
lethal food & D/I
2. Hypertensive rx , esp
when high-tyramine
foods (smoked/ pickled
meats, sauerkraut, soy
sauce, fava beans,
cheeses) ingested by
patients who are taking
them.
