October 19 Norepinephrine and Dopamine

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• October 19 -Norepinephrine and Dopamine
• Catecholamines
• Norepinephrine, epinephrine and dopamine
• Share certain stages of synthesis pathway
• Similar chemical structure
• Share certain breakdown enzymes
• Drugs often act on all 3
• Norepinephrine both CNS and Sympathetic Nervous
  System
• Dopamine mostly CNS
• Epinephrine (adrenalin) mostly PNS also made
  by adrenal gland

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II. Synthesis Tyrosine (from food) ----1----?
dopa 1 tyrosine hydroxylase rate limiting
enzyme Dopa ----2----?dopamine 2 dopamine
decarboxylase Dopamine ----3----?
norepinephrine 3 dopamine beta-oxidase Norepine
phrine ----4----? epinephrine 4
phenylethanolamine-N-methyl-transferase (PNMT)
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• II. Synthesis
• Presence of a specific set of enzymes determines
  which neurotransmitter is made in neuron
• Cells in adrenal gland have all 4 enzymes and
  make epinephrine as hormone
• All 3 neurotransmitters share tyrosine
  hydroxylase as rate limiting step

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• III. Termination of action and degradation of NE
  and DA
• Activity terminated primarily by reuptake into
  neurons or glia
• Following reuptake, breakdown inside neurons or
  glia is by monoamine oxidase (MAO)
• By-products are metabolized and excreted
• NE is broken down into vanillylmandelic acid
  (VMA) and MHPG index of NE activity
• DA broken into homovanillic acid (HVA) index of
  DA activity
• Also some NE and DA broken down in synaptic space
  by catechol-o-methyl-transferease (COMT)

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• III. Termination of action and degradation of NE
  and DA
• IV. Epinephrine
• Role in brain is poorly understood
• E appears to modulate NE in certain locations
• Adrenal gland (adrenal medulla part) secretes
  epinephrine and norepinephrine during stress or
  emotional arousal
• This source of epinephrine and norepinephrine
  acts as hormones (travels in blood to sites of
  action)
• E important in blood pressure regulation,
  coordination of eating and visceral activities

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The Human Nervous System
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Aim in
Exit
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• III. Termination of action and degradation of NE
  and DA
• IV. Epinephrine
• V. Norepinephrine
• Manufactured by cells in adrenal medulla and in
  CNS and PNS
• NE in the Peripheral Nervous System
• In sympathetic nervous system, preganglionic
  fibers use acetylcholine, postganglionic release
  NE. Target organs in sympathetic system respond
  to NE.
• Excitation of heart inc. blood pressure
  vasoconstriction
• increased breathing rate bronchodilation
• pupils dilate sweating
• shunts blood to brain and muscle
• increases glucose conversion to energy

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• V. Norepinephrine
• NE in the PNS
• In sympathetic nervous system, preganglionic
  fibers use acetylcholine, postganglionic release
  NE. Target organs in sympathetic system respond
  to NE.
• Drugs which mimic NE in sympathetic nervous
  system are called sympathomimetics (also
  influence E and DA in peripheral nervous system)
• Sympathomimetics used to treat blood pressure
  (hypotension shock) asthma heart failure or
  arrhythmias (stimulate heart) decongestants
  incontinence

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• V. Norepinephrine
• NE in PNS
• In sympathetic nervous system, there are 4 types
  of NE receptors
• alpha1 excitatory
• contraction of vascular smooth muscle
  (treatments for hypotension)
• contraction of urinary smooth muscle
  (treatments for incontinence)
• contraction of nasal mucosa and muscle
  (treatments for nasal swelling
  decongestants)
• Drugs in use do not cross the blood-brain
  barrier

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• V. Norepinephrine
• In sympathetic nervous system, there are 4 types
  of receptors
• alpha1 hypotension incontinence decongestants
• alpha2 inhibitory no relevant PNS only drugs.
• alpha2 receptors also found in CNS
• when bound, inhibit the release of NE from
  sympathetic neurons and reduce excitation of
  heart
• treat high blood pressure (hypertension)
• Clonidine reduces blood pressure and heart
  rate also used to ease certain withdrawal
  symptoms

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In sympathetic nervous system, there are 4
types of receptors alpha1 hypotension
incontinence decongestants alpha2 inhibitory
treat hypertension and withdrawal excitation of
heart Beta1 excitatory increase blood
pressure and heart rate Beta blockers
Propanolol Atenolol stage fright and panic
symptoms (acute) - chronic treatment of high
blood pressure
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alpha1 hypotension incontinence
decongestants alpha2 inhibitory treat
hypertension and withdrawal excitation of
heart beta1 excitatory increase blood
pressure and heart rate (Beta blockers act
here) beta2 excitatory or inhibitory relax
smooth muscle of blood vessels bronchi GI
tract urinary tract increase carbohydrate
and fat metabolism in liver and muscle
stimulate conversion of glycogen to glucose in
liver
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V. Norepinephrine A. NE in the PNS Non-selective
Beta agonists 1 and 2 older inhalers for
asthma isoproteranol side effects of heart
stimulation Newer Beta2 agonists Alupent
Albuterol (Ventolin) Metaprel more selective
less stimulation of heart B. NE in the CNS
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• A. NE in the PNS
• B. NE in the CNS
• Most NE releasing neurons are unmyelinated with
  highly branched axon terminals
• 2 major pathways from brainstem
• 1. From locus coeruleus to multiple subcortical
  and cortical sites
• Locus coeruleus large cluster of neurons at
  core of pons 12000 on each side that send axons
  over broad network
• Project to hippocampus, thalamus, hypothalamus,
  olfactory bulb, cerebellum, cerebral cortex
• Mostly act at beta adrenergic receptors -
  inhibitory

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• B. NE in the CNS
• 2 major pathways from brainstem
• 1. From locus coeruleus to multiple subcortical
  and cortical sites
• Locus coeruleus large cluster of neurons at
  core of pons 12000 on each side that send axons
  over broad network
• Project to hippocampus, thalamus, hypothalamus,
  olfactory bulb, cerebellum, cerebral cortex
• Mostly act at beta adrenergic receptors
  inhibitory
• Inhibit background discharge rates of multiple
  neurons in above areas, especially cortex
  causes global orientation to stimuli positive
  feelings of emotion involved in basic drive
  states (hunger (suppression) thirst sex)

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• B. NE in the CNS
• 2 major pathways from brainstem
• 2. Lateral tegmental area (outside of LC but
  same area) to descending and ascending paths
• - descending to midbrain, brainstem, and spinal
  cord
• - ascending to amygdala, septum, hypothalamus
  and thalamus
• Some excitatory some inhibitory actions
• Intermingled with axons from neurons in LC
  pathway hard to study
• Receptor types are unclear alpha and beta both.
  
• Involved in positive emotion drive states and
  analgesia

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• B. NE in the CNS
• C. Important Diseases/Drugs
• Depression and mania
• Certain antidepressants
• Stimulant drugs (low doses) amphetamine and
  cocaine
• PNS acting drugs already mentioned
  (decongestants asthma inhalers blood pressure
  meds)
• Also important for the side effects of many meds
  used to treat Sz

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• Serotonin
• Serotonin is used throughout the body in multiple
  physiological roles.
• 90 of all serotonin in human body is in the GI
  tract
• 8 in blood platelets
• 2 in CNS
• Neurons in brain make their own none from body
  crosses BBB

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Serotonin A. Synthesis Made from Tryptophan
amino acid from diet Need 12-13 protein intake
to provide what brain needs. Tryptophan is
actively transported into neurons from
blood. Must compete with other amino acids
(tyrosine phenylalanine) for entry Due to
competition, dietary protein and carbohydrate
content are important.
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• A. Synthesis
• Tryptophan ---1--? 5 hydroxytryptophan
• 5 hydroxytryptophan -- 2--? 5 hydroxytryptamine
• 1 tryptophan hydroxylase rate limiting step
• High serotonin levels within neuron do not
  inhibit enzyme synthesis serotonin just builds
  up (when MAO blocked, etc)
• Rate of enzyme activity can be modulated by
  second messengers involving cAMP
• also can be modulated by Oxygen levels in blood
  more oxygen, more synthesis of serotonin

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• A. Synthesis
• Tryptophan ---1--? 5 hydroxytryptophan
• 5 hydroxytryptophan -- 2--? 5 hydroxytryptamine
• Serotonin (5HT)
• 2 5 hydroxytryptophan (5HTP) decarboxylase
• This enzyme very similar to dopa decarboxylase
• Production of enzyme and use to make serotonin
  very rapid
• Cannot manipulate serotonin by manipulating this
  enzyme
• Release of serotonin is Ca dependent Ca
  must come in to trigger release

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• Synthesis of Serotonin
• Deactivation and breakdown
• Action terminated by active reuptake process into
  neurons and glia
• Then broken down by MAO
• MAO breaks down 5HT into several things
• 5-hydrozyindoleacetic acid (5HIAA) is a
  metabolite that is often used to index activity
  in system measured in CSF (cerebrospinal fluid)
• C. Receptors

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• Synthesis of Serotonin
• Deactivation and breakdown
• C. Receptors
• 7 major types 3 of relevance to current set of
  medications
• 5HT1 slow inhibition through G proteins,
  reduce adenylyl cyclase activity exists as
  postsynaptic and presynaptic receptors
• 5HT2 slow excitation through G proteins,
  increase K and Ca influx. CNS has mostly
  5HT2A (found in prefrontal cortex)
• 5HT3 fast excitation (ion-coupled receptor
  Na some modulation also of Ca channels) in
  area postrema, trigger vomiting

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• Synthesis of Serotonin
• Deactivation and breakdown
• C. Receptors
• D. Pathways in brain
• Serotonin released as neurotransmitter but also
  released non-synaptically through some axon
  terminals (may act on tone of intracranial blood
  vessels relevance to migraine)
• 9 neurotransmitter pathways can be consolidated
  into 3 major paths
• All paths emerge from same set of neurons in the
  Raphe region of the brainstem a group of nuclei
  along midline of midbrain, pons, and medulla

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• D. Pathways in brain
• Caudal pathway from Raphe nuclei to medulla and
  spinal cord
• Uses mainly 5HT2 receptors slow excitation
• Causes contraction of smooth muscle in gut
  gastric motility
• Causes contraction of uterine muscles - cramps
• Causes some contraction of blood vessel walls
  blood pressure
• Causes mild motor neuron excitation
• Stimulates release of endorphins that then
  inhibit pain messages carried by substance P (nt
  that is a pain messenger) analgesia
• 5HT3 receptors in Area Postrema trigger vomiting

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• D. Pathways in brain
• Caudal pathway from Raphe nuclei to medulla and
  spinal cord
• Uses mainly 5HT2 receptors slow excitation
• 2. Middle pathway from Raphe neurons to
  cerebral cortex and basal ganglia
• Goes to cortex along with NE axons
• Goes to basal ganglia along with DA and ACh
  neurons
• 5HT2 (slow excit) 5HT3 (fast excitation)
  receptors
• indirectly inhibits mesolimbic and nigrostriatal
  dopamine activity (blockade increases DA action
  in some areas)
• serotonin induces positive mood and affect
  cortex
• This is the system where SSRIs work by inhibiting
  the transporter protein necessary for serotonin
  reuptake

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• D. Pathways in brain
• 2. Middle pathway from Raphe neurons to
  cerebral cortex and basal ganglia
• 5HT2 (slow excit) and 5HT3 (fast excitation)
  receptors
• modulates movement
• induces positive mood and affect cortex
• SSRIs Ecstasy
• 5HT2A blocked by new antipsychotics inhibits
  excess DA function
• Rostral pathway Raphe nuclei to 5 areas
• Uses 5HT1 (slow inhibition) and 5HT2 (slow
  excitation)

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• D. Pathways in brain
• 3. Rostral pathway Raphe nuclei to 5 areas
• Uses 5HT1 (slow inhibition) and 5HT2 (slow
  excitation)
• a. Raphe nuclei (within)
• Within Raphe, there are autoreceptors (5HT1
  self inhibit)
• b. Raphe to sensory cortex
• Sensory cortex - particularly visual perception
  5HT2 -relevant to hallucinogens (LSD psilocybin
  mushrooms)
• c. Raphe to limbic system
• Limbic system pleasure anxiety slow
  inhibition at 5HT1 receptors
• BuSpar (buspirone) binds with 5HT1 receptors here
  and helps reduce anxiety

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• D. Pathways in brain
• Rostral pathway
• a. Raphe nuclei (within)
• Within Raphe, there are autoreceptors (5HT1
  self inhibit)
• b. Raphe to sensory cortex
• c. Raphe to limbic system
• Limbic system pleasure anxiety slow
  inhibition at 5HT1 receptors
• d. Raphe to hypothalamus and thalamus
• Uses 5HT1 receptors in thermoregulation
• Ecstasy causes elevated body temp thru here

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• D. Pathways in brain
• Rostral pathway
• c. Raphe to limbic system
• Limbic system pleasure anxiety slow
  inhibition at 5HT1 receptors
• d. Raphe to hypothalamus and thalamus
• Uses 5HT1 receptors in thermoregulation
• Ecstasy causes elevated body temp thru here
• e. Raphe to suprachiasmatic nucleus
• Uses 5HT1- slow inhibition
• Important in sleep/wakefulness

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• D. Pathways in brain
• Rostral pathway
• e. Raphe to suprachiasmatic nucleus
• Uses 5HT1- slow inhibition
• Important in sleep/wakefulness
• Serotonin induces sleep inject into brain,
  sleep occurs
• Inhibit serotonin (by PCPA, inhibits tryptophan
  hydroxylase and production of serotonin) no
  sleep increased activity
• But other neurotransmitters also important in
  sleep

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• E. CNS Relevant Diseases/Drugs
• depression
• anxiety
• possibly some interactive role in schizophrenia
• migraine headaches 5HT1 agonists cause
  constriction of intracranial blood vessels may
  block endogenous inflammatory agents
• LSD and psilocybin mushroom hallucinogens
• Ecstasy empathogen
• high levels of amphetamine

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Antidepressants
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• Biological Causes of Depression
• (history NE hypothesis SE hypothesis)
• 1. Genetic influences
• Monozygotic twins - 40-65 concordance (chance
  that if one twin has it, the other does too)
• Dizygotic twins - 10-20 concordance
• 2. Neurochemical characteristics
• a. reduced levels of metabolites of
  norepinephrine in cerebrospinal fluid and urine

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• 2. Neurochemical characteristics
• b. abnormal endocrine functions controlled by
  norepinephrine
• High cortisol levels - dysfunction in
  hypothalamic-pituitary-adrenal axis control
  system
• Neurons in hypothalamus use NE as the
  neurotransmitter that tells other hypothalamic
  neurons to stop releasing CRF

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The hypothalamic-pituitary-adrenal axis Stress
stimulates neurons in the hypothalamus to release
corticotropin-releasing factor (CRF) CRF
stimulates limbic system- emotional
response CRF stimulates anterior pituitary to
release adrenocorticotrophic hormone
(ACTH). ACTH stimulates release of
glucocorticoids from the adrenal cortex.
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• 2. Neurochemical characteristics
• b. abnormal endocrine functions controlled by
  norepinephrine - high cortisol levels
• c. abnormal response on dexamethasone suppression
  test
• Dexamethasone - synthetic cortisol.
• Measure cortisol levels at 1100 PM
• Then give dexamethasone.
• Next day, should have lower cortisol.
• Not so in many depressed people.

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• 2. Neurochemical characteristics
• d. reduced levels of metabolites of serotonin
  (respond to drugs that increase serotonin)
• e. Increased density of NE and 5HT2
  receptors
• f. Serotonin plays an important role in blood
  platelets which helps protect them from excess
  clumping. Among depressed, more platelet
  aggregation is seen, along with increased risk
  for heart attack and stroke.
• g. drugs that block or deplete NE or SE can cause
  depression (Reserpine and certain drugs used to
  treat high blood pressure)

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• 2. Neurochemical characteristics
• g. drugs that block or deplete NE or SE can cause
  depression
• h. animals showing learned helplessness have
  reduced levels of NE and SE (and elevated
  cortisol)

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• 3. Illnesses that may produce depression
• Cushings Syndrome
• Pituitary tumors produce too much ACTH --gt then
  adrenals release too much cortisol
• or
• Adrenal tumors may produce too much cortisol.
• Excessive treatment with corticosteroids may
  mimic syndrome.
• All causes lead to obesity and unusual body hair
  growth

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• 3. Illnesses that may produce depression
• Cushings Syndrome (85 )
• Thyroid disorders (underactive - depression
  overactive - excessive energy reduced sleep
  needs possible mania) certain toxicants are
  thyroid disruptors
• Parkinsons Disease (50)
• Substance abuse disorders
• Long term use of certain drugs at high levels
  alters relevant neurochemical systems (NE, DA,
  SE) - Cocaine, Methamphetamine Ecstasy.

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• Suicide
• 80 of those who commit suicide suffer from
  depression or bipolar disorder
• among the depressed, 15 commit suicide each year
• suicide victims have lower concentrations of
  serotonin in their brain
• suicide victims show high levels of cortisol

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• General Health
• Depression increases the risk of dying after
  heart attack or stroke.
• Chronic overactivation of the stress circuit
  increases risk for heart disease and stroke.

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• Drugs Used to Treat Depressive Disorders
• MAO inhibitors
• 2. Tricyclic antidepressants
• 3. Selective Serotonin Reuptake Inhibitors

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• II. Antidepressants
• A. Monoamine Oxidase Inhibitors
• in early 1950s, iproniazid, used to treat
  tuberculosis, was noted to elevate mood
• use as antidepressant began in late 1950s, but
  caused liver toxicity
• other drugs then developed, but use has always
  been limited by severe side effects
• second line med - play a role in treating
  treatmentresistant

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• Pharmacodynamics
• inhibition of monoamine oxidase(s) the enzyme
  family that breaks down monoamine transmitters,
  NE, E, DA, SE following reuptake
• there are 2 MAO types A and B
• MAO A breaks down E, NE, DA, and SE within
  neurons and some glial cells
• MAO B breaks down DA in nigrostriatal regions
  also breaks down tyramine and other substances in
  neurons and some glial cells (protects the
  neuron)
• does not break down the neurotransmitters inside
  vesicles only the ones found or reuptaken into
  cytoplasm
• in gut, MAOs, especially MAO B break down
  several food stuffs importantly tyramine

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A. Monoamine Oxidase Inhibitors (MAO B also in
gut) Phenylzine (Nardil) - non-selective and
irreversible Isocarboxazid (Marplan) -
non-selective and irreversible Tranylcypromine
(Parnate) - non-selective and irreversible Selegil
ine (Eldepryl) selective B, irreversible Moclobe
mide (Manorix Aurorix)- selective A and
reversible Brofaromine (Consonar) - selective A
and reversible Taken orally Delayed
action Efficacy of 70-80 for reduction of
depressive symptoms.
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• Unpleasant, possibly Life-Threatening Drug-Food
  Interaction
• in gut, MAOs, especially MAO B break down
  several food stuffs importantly tyramine
• inhibition of breakdown by MAO due to these
  drugs leads to buildup of tyramine which causes
  toxic sympathomimetic effects
• these coupled with elevated actions of NE lead
  to dangerous hypertensive crisis elevated blood
  pressure heart rate increase, severe occipital
  headache motor agitation, sweating -gt if
  untreated, stroke, loss of consciousness, death
• effects occur in 20 min- 1 hour after ingestion
  of the food containing tyramine
• must avoid aged foods cheese, sausages,
  alcohols, sauerkraut, pickled or fermented foods,
  and others

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Other Side Effects Dizziness Fatigue Headache
Jaundice Dry mouth Anorgasmia Insomnia
Erectile dysfunction Postural hypotension
Blurred vision Urinary retention/hesitancy
Nausea Peripheral edema Constipation Muscle
weakness/jerking Multiple reasons beyond just
brain-based actions.
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• B. Tricyclic Antidepressants (and tetracyclic)
• main treatment for depression from 1960-1980
• still among best treatments for the moderately
  to severely depressed (non-delusional) person
  80 response
• many side effects and poor safety margin
• oldest is Imipramine (Tofranil)
• 10 are on US market

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B. Tricyclic Antidepressants (and
tetracyclic) Imipramine (Tofranil) Desipramine
(Norpramin) Amitriptyline (Elavil) Nortriptyline
(Aventyl Pamelor) Clomipramine
(Anafranil) Trimipramine (Surmontil) Doxepin
(Sinequan Adapin) Protriptyline
(Vivactil) Amoxapine (Asendin) Maprotiline
(Ludiomil)
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• Pharmacokinetics
• Well absorbed orally
• Peak in 2-6 hours
• Individual differences in metabolism slow
  metabolizers and fast metabolizers
• Liver metabolism by CYP2D6
• Renal clearance
• Most TCAs have half-life around 24 hours
• Allows once/day dosing for all
• Elderly may need lower doses
• Very narrow therapeutic index 6-10 with fatal
  cardiac arrhythmias as cause of death (can
  overdose on a 1 week supply)
• Plasma concentrations are monitored

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• Pharmacodynamics
• vary in ratio of blocking NE and SE reuptake
  all block NE
• also block muscarinic cholinergic receptors,
  alpha receptors for NE in PNS, and histamine
  receptors
• Actions on NE (and SE) occur within hours, but
  depression reduction takes 1-2 weeks Why?
• 1. Receptor Sensitivity Hypothesis correlates
  of depressive symptom reduction
• With repeated increase in the NE supply due to
  tricyclic action, beta adrenergic receptors for
  NE in brain down regulate by reducing in number
• Also enhanced serotonergic transmission at 5HT1A
  receptors alongside down regulation of 5HT2
  receptors

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1. Receptor Sensitivity Hypothesis correlates
of depressive symptom reduction With repeated
increase in the NE supply due to tricyclic
action, beta adrenergic receptors for NE in brain
down regulate by reducing in number Also enhanced
serotonergic transmission at 5HT1A receptors 2.
May stimulate neuronal proliferation and increase
number of neurons in limbic areas (fits with idea
that stress ultimately destroys hippocampal
neurons as part of how chronic stress may cause
depression)
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Tricyclic Action Side effects

• Reuptake blockade of NE heart arrhythmias
• Blockade of Muscarinic Receptors Dry mouth and
  eyes
• (anticholinergic effects) Urinary retention
• Constipation
• Blurred vision
• Confusion-gt Delirium
• Blockade of alpha-NE Postural hypotension
• receptors in the PNS Dizziness
• (anti-adrenergic effects) Drowsiness
• Blockade of histamine receptors Sedation
• Weight gain
• (15 lbs in 6mo)

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• Tricyclic Antidepressants Drug Interactions
• based on liver enzyme competition or induction
• Prozac and TCAs TCA levels build up to
  dangerous level
• MAOIs also dangerous stroke seizures
• Haloperidol and Phenothiazines (antipsychotics)
  can block metabolism of TCAs they build up
• Barbiturates induce metabolism - need higher
  dose of TCAs
• Phenytoin (Dilantin) Phenytoin may be elevated
  into toxic range

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• C. Selective Serotonin Reuptake Inhibitors
  SSRIs
• first one, Prozac, entered US market in 1987
• in 1988, sales of Prozac matched that for all
  antidepressants combined in 1986
• strong promotion as equal efficacy (70) but
  with fewer side effects, easier standardized
  dosing, no need for blood monitoring, and greater
  safety
• equal efficacy plus can treat people who could
  not take alternative meds due to side effects and
  personal health characteristics (70 respond) or
  who did not respond to other meds (50-60
  respond)
• also used for certain anxiety disorders, eating
  disorders, and post-addiction therapies

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SSRIs Fluoxetine (Prozac) Depression, Bulemia,
OCD Fluvoxamine (Luvox) - OCD Citalopram (Celexa)
- Depression Sertraline (Zoloft) Depression,
OCD, Panic Disorder, Paroxetine (Paxil)
Depression, OCD, Panic, Social Anxiety
Disorder All SSRIs share similar pharmacodynamic
action, efficacy, ease of dosing, and somewhat
similar side effect profiles in large group
studies (but individual differences lead some to
prefer one over another)
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• Pharmacokinetics
• oral dosing with little variability in needs
  across people
• Prozac standardized dose is 20-40 mg/day orally
  (may be elevated to 60-80 if no response)
• one Prozac death recorded at overdose of 7000 mg
  wide safety margin TI much above 100 (one
  attempted overdose of 12000, but threw up)
• does bind with blood proteins (94 of dose),
  must saturate first then efficacy in about 1 week
  (not 2 as for tricyclics)
• metabolized by liver CYP2D6 so some drug
  interactions and variability across slow vs fast
  metabolizers

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• Pharmacodynamic Action
• inhibit the serotonin reuptake transportor more
  potently than NE or DA
• far less potent binding to muscarinic receptors
  for Ach than tricyclics, hence fewer
  anticholinergic side effects
• far less potent binding to histamine receptors
  than tricyclics, hence fewer side effects of
  sedation
• need to taper dose to reduce withdrawal signs

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Side Effects ( are for Prozac) Anxiety,
nervousness, insomnia 10-15 Appetite
suppression 9 of people (not weight gain, but
loss of 5 of bodyweight) Nausea, dizziness,
headache 5 Allergic skin rash 4 Mania 1
rate (about same as for Tricyclics) Seizures -
lt1 - but not used in seizure-disordered patients
due to interactions with Phenytoin and
Tegretol Hypoglycemia during use and
hyperglycemia on withdrawal careful monitoring
or exclusion of use in diabetic patients Sexual
dysfunction impotence, ejaculatory disturbance
(perhaps less for Prozac and Luvox)
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Drug Interactions Tricyclics - enzyme
competition Carbamazepine(Tegretol)and Phenytoin
(Dilantin) Dextromethorphan MAOI can experience
fatal effects serotonin syndrome