LIMITATIONS 1

At the molecular level, an explanation

of the action of a drug is often
possible; at the cellular level, an
explanation is sometimes possible;
but at a behavioral level our
knowledge is abysmal.

- Cooper, Bloom, and Roth

The Neurochemical Basis of
Neuropharmacology 1
 LIMITATIONS 2
 Complexity
 high patient variability
 Slow rate of recovery

 Limited evidence
 Empiric, inference
 trial and error

 Non TBI population

2
 NEURODEVELOPMENT
 Neuron Formation: most by 2nd trimester of prenatal life
 Neuron migration: complete by birth
 Adult size brain: ~5 yrs old.
 Synapses: Peak in childhood ~6 yrs. old
 Synapse remodeling/restructuring/turnover :most
rapid at puberty
 Synapse survival: only ½ -2/3 of synapses at peak survive
into adulthood

3
THE BRAIN?

7
 NEUROTRANSMITTER
THEORY
BIOLOGY
FUNCTION
Neurotransmission Cognition
Synapse Connections Behavior
Motor
Sensory

ENVIRONMENT

5
WHAT WE DO KNOW?
LIGAND (neurotransmitters)

RECEPTOR

ION CHANNELS
2nd MESSENGER SYSTEMS
MOLECULA
R?
(ligand,receptors,ions)
I

CELLULAR??
(DNA,gene transcription/translation/expression, products)
NEURON GROWTH/DEATH)

ORGAN???
SYNAPSE RESTRUCTURING, NEUROPLASTICITY

FUNCTION(BEHAVIOR) ????
MOTOR, SENSORY,BEHAVIORAL, COGNITIVE, PSYCHO, SOCIAL 6
 LIGAND -
NEUROTRANSMITTERS
 TABLE 4
 Amino acids:
glutamate
 Peptides:
serotonin
 Hormones:
estrogen
 Lipids:
Orphan Receptors
anandamide
 Gases: CO
 Neurokinins/tach 7
 BUILDING BLOCKS
I. ALTERING NEUROTRANSMITTER
LEVELS
I. INCREASE
 Increase substrate for production
 Increase release
 Agonist spectrum
 Decrease breakdown
II. DECREASE
I. Decrease release
II. Increase breakdown
III. Antagonist spectrum
II. Neurotransmitter systems interact
with one another!!
I. INHIBITION, MODULATION,
AUGMENTATION 8
 DRUG SELECTION IN BI
 SIDE EFFECTS: cognitive
 OTHER DRUG EFFECTS
 UNIQUE TBI BRAIN:hypersensitivity, decreased seizure
threshold, etc..
Vulnerability to:
 DRUG INTERACTIONS
Behavior disorder
 PREVIOUS HX: Genetic and external factors
Response to drugs
 MEDICAL
 PSYCHIATRIC
 AGE : Maturity of nervous system/ neuroplastic potential
 SOCIAL-LIFE STRESSORS
 PREMORBID PERSONALITY&COPING SKILLS,
 SUBSTANCE ABUSE
 DRUG:onset of action, duration
 Dependent on postsynaptic activity.
 LIGAND GATED ION CHANNEL VS. SECONDARY MESSENGER
CASCADE.
9
DRUG ONSET OF ACTION

19
 PRIORITIZING
COMMON BEHAVIORAL ISSUES:ONE THING LEADS TO
ANOTHER?…
 CENTRIPETAL MODEL OF RECOVERY
 SLEEP AROUSALATTENTION

 COGNITION
 MEMORY, LEARNING, VIGILANCE, EXEC FUNCTION
 SOCIAL BEHAVIOR
 REPONSE TO SOCIAL CUES
 SPEECH
 VERBAL FLUENCY
 MOOD/AFFECT “AGITATI
 DEPRESSION ON”
 REALITY CHECK
 PSYCHOSIS

 OTHER
 MOTOR, ENDOCRINE, GI, CV, APETITE, REWARD, PAIN

 COMPLEX INTERACTIONS 11
 APPROACH
TO ALTERING NEUROTRANSMITTER LEVELS?

 NON-PHARM
 CHANGE ENVIRONMENT
 Avoid restraints, provide safe & protected
environment, minimize stimuli, mobilization
 R/O REVERSIBLE MEDICAL CAUSES
 Pain, hypoxemia, hydrocephalus, metabolic
or endocrine disorder
 R/O OTHER DRUG EFFECTS/TOXICITY
 Minimize and substitute drugs w/ less side
effects
 PHARM
12
 SLEEP 1
 SLEEP – WAKE CYCLE
 REM VS NREM SLEEP
 PHYSIOLOGICAL CIRCADIAN RHYTHM

 NOT AROUSAL OR COMA

 INCREASED DAYTIME
SOMNOLENCE
 R/O SECONDARY CAUSES
 HYPOXEMIA, OSA, CO2 RETENTION,
METABOLIC, SEIZURES, DRUG SIDE EFFECTS
13
 SLEEP 2
 NEUROTRANSMIT  NON-PHARM
TERS  Rule out & treat
 SEE TABLES 1-2 SECONDARY
 SLEEP CAUSES
 Pain, other behavior
 Serotonin
disorder
 GABA
 Good SLEEP
 WAKEFULNESS
HYGIENE
 Norepinephrine  Decrease environ
 Epinephrine stimuli
 Dopamine  Set WAKE
 Histamine
PATTERN
 Acetylcholine  Introduce env. 14
stimuli
SLEEP
DRUG CLASS EXAM PLES M ECHANISM OF ACT ION ADVANT AGES

NON BZD SHORT ACTING

HYPNOTICS rapid onset, short duration; less cog side effe
less tolerance, dependence; less rebound
zolpide m-a mbie n insomnia (as compared with slower onset, lo
za le pon-sona ta omega 1 GABA agonist duration, non-specific hypnotic BZD hypnotic
SED-HYPNOTIC BENZD

fluraze pa m-
da lma ne GABA agonist
ANTIDEPRESSANTS W/ SED-
HYPNOTIC QUALITY

a mitriptyline -
e la vil anticholinergic
antihistamine
alpha 1 adrenergic blockade

norepi reuptake inhibitor

TCA serotonin reuptake inhibitor

serotonin is a neurotransmitter normally invol
sleep generation, less agitation and insomnia
anxiety S.E. than other serotonergic agents;
tra za done -de syrel 5HT2A antagonist CV and anticholinerg
serotonin reuptake inhibitor
serotonin antagonist,/reuptake anticholinergic relative dearth of anticholinergic and CV S.E.
inhibitor antihistamine
OTC
sleeping pills anticholinergic
antihistamine FOCUSON RESTO
OTHER NONBENZO SED-

A NORMAL SLEEP
HYPNOTICS
BARBITURATES GABA rapid onset
ETHCHLORVYNOL
ETHINAMATE
PIPERIDINEDION AND
DERIVATIVES
CHLORAL HYDRATE AND DON’T CONFUSE
DERIVATIVES
NATURAL PRODUCTS
MELATONIN
VALERIAN
SEDATING SIDE EF
natural products, OTC

WITH IMPROVED S
PATTERNS
BEAWARE OF
COGNITIVE SIDE
15
E
 MOOD
 DEFINITION: Internal emotional
condition
 AFFECT: expression of that condition
 TYPES:
 DEPRESSION
 MANIA/HYPOMANIA
 BIPOLAR

16
 MOOD – DEPRESSION 1
 NEUROTRANSMITTERS
 MONOAMINE DEFICIENCY
 norepinephrine
 dopamine
 serotonin

17
MOOD-DEPRESSION
CLASS EXAM PLES M ECHANISM S OF ACT ION ADVANT AGES

ANTIDEPRESSANTS
inhibits momoamine oxidase

Monoamine oxidase inhibitor phenelzine-nardil

inhibits serotonin reuptake

inhibits norepinephrine reuptake

blocks histamine

blocks M1 cholinergic receptor

Tricyclic antidepressant amitriptyline-elavil

selectively blocks serotonin reuptake more effective for those w/ serotonin
defociency syndrome: depression w/
anxiety, panic, phobia, PTSD,
compulsions, eating disorders
selective serotonin reuptake inhibitor fluoxetine-prozac
selectively blocks norepinephrine reuptake more effective for those
w/noradrenergic deficiency
syndrome:depression w/
fatigue,apathy ,slow processing,
slective noradrenergic reuptake inhibitor reboxetine-edronax inattention; unresponsive to
inhibits dopamine reuptake serotonergic agents

Norepinephrine- dopamine reuptake inhibitor buproprion-w ellbutrin inhibits norepinephrine reuptake

inhibits seotonin reuptake
Serotonin-norepinephrine reuptake inhibitor
venlaxafine-effexor inhibits norepinephrine reuptake
blocks alpha 2 noradrenergic receptor
blocks serotonin 1,2A&C,3 receptors anxiolytic, less sexual S.E., less GI
S.E. as compared with other
alpha 2 noradrenergic -specific serotonin antagonist mirtazapine-remeron serotonergic agents

VARIABLE SIDE EFFECT

blocks serotonin 2A receptor serotonin is a neurotransmitter
normally involved in sleep generation,
Serotonin antagonist/reuptake inhibitors less agitation and insomnia, anxiety

PROFILES Dependent on
blocks serotonin reiptake S.E. than other serotonergic agents.

alpha adrenergic blockade (weak)

various mechanisms of action

blocks histamine
trazadone-desyrel
blocks M1 cholinergic receptor (weak) relative dearth of anticholinergic side eff
MONOAMINERGIC MODULATORS beta adrenergic agonist none found that can pas blood-brain bar
beta agonists
2nd messenger system rolipram
RECEPTOR
serotonin 1A partial agonist; augments ?rapid onset?
serotonin 1A agonist,partial agonist,or antagonist buspirone-buspar SSRI
serotonin-dopamine reuptake inhibitor

serotonin 1D antagonist minaprine

DOWNREGULATION: May
inhibits seotonin reuptake
inhibits dopamine reuptake
blocks serotonin 1D receptors
clinical testing in progress

NEUROKININ ANTAG
NOVEL MECHANISMS
SR 140333
explain time to clinical onset
clinical testing in progress
in early testing phases
neurotensin neurotensin
cck cck
as well as tolerance and
decrease of side effects over
18
time.
29
RECEPTOR DOWNREGULATION

3
 DEPRESSION 2
 TRAZADONE as sleep agent
 Serotonergic agent that restores sleep
without the stimulating side effects of
other SRI’s.
 Relative dearth of anticholinergic and
cardiovascular side effect of other SRI’s.

21
AROUSAL/attention/psychomo
tor/cognitive
 A COMPONENT OF WAKEFULNESS?
 General state of readiness of an individual to
process sensory information and/or organize a
response.
 HYPERAROUSAL
 Psychomotor
restlessness,”agitation”,decreased attention
(hyperactive,impulsive,distractible), cognitive
deficits.
 HYPOAROUSAL
 NOT COMA: no sleep-wake cycles in coma
 Psychomotor retardation, decreased attention,22
ATTENTION

33
arousal/ATTENTION/psychom
otor/
cognitive
 DEFINITION
 Volitional Channeling of arousal toward a
chosen stimuli while inhibiting unwanted
extraneous stimuli.
 ATTENTION DEFICIT
 DISTRACTABLE (By internal and/or external
stimuli )
 PSYCHMOTOR RESTLESSNESS:
hyperactive,impulsive.
 EXAMPLES
 ADD
 ADHD 24

arousal/ATTENTION/psychom
otor/
cognitive
 “HYPER-ATTENTION”?
“
 actually an attention deficit as well.
 E.g: Hyper vigilance, perseveration,
stimulus bound.
 Don’t confuse with psychotic delusions

 Inability to volitionally inhibit stimuli

long enough to selectively change and
channel the focus of arousal toward
another chosen stimuli.

25
Arousal/attention/PSYCHOMO
TOR/
cognitive
 INCREASED PSYCHOMOTOR
ACTIVITY
 E.g.: restlessness,akisthisia
 Don’t confuse with agitation or angry
affect.

 PSYCHOMOTOR RETARDATION
 E.g.: poor motivation,poor
initiation,anhedonia,
26
arousal/attention/psychomotor/
COGNITIVE
 SUSTAINED AND FOCUSED ATTENTION IS
KEY
 Vigilance for executive function
 Prioritizing behavior
 Modulating behavior based on social cues
 Verbal fluency
 Serial learning
 Processing speed
 flexibility
 Multi-tasking
 ADDRESSING OTHER
PSYCHOBEHAVIORAL DISORDERS
WILL ALSO IMPROVE COGNITION.
27
AROUSAL/ATTENTION/PSYCHO
MOTOR/COGNITIVE:
NEUROSTIMULANTS
 NEUROTRANSMITTERS
 DOPAMINE: more abuse potential,
more potent stimulant
 NORADRENERGIC: more sympathetic
tone and side effects

28
COGNITIVE
CLASS EXAM PLES M ECHANISM OF EFFECT ON NT ADVANT AGES
DOPAMINERGIC
ACT ION LEVELS
inhibits dopamine reuptake?, acts
modafinil at brainstem sleep-wake centers

methylphe nidate-ritalin inhibits dopamine reuptake

increase dopamine release
D-a mphe tamine-adderall ditto

m-amphe ta mine ditto

increase catecholamine release,
others
pemoline -cylert ditto
L-dopa dopamine precursor
DRI bromocriptine-pa rlodel presynaptic D2 agonist

COMT inhibitor a ma ntadine-symmetrel inhibitd dopamine breakdown

D1 and D2 agonist pergolide D1 and D2 agonist

More potent stimulant

NORADRENERGIC
alpha 2 agonist alpha 2 agonist  decrease presynaptic epinephrine
release, postsynaptic alpha2 partial
less noradrenergic side effects

clonidine-catapres agonist

NRI a tomoxetine-strattera
inhibits norepinephrine reuptake

inhibits norafrenergic reuptake

effect higher abuse
NRI antidepressants reboxe tine-edronax potential
DOPAMINERGIC/

Stimulant effect:
NORADRENERGIC-
ANTIDEPRESSANTS 
Dopamine>norepinephri
inhibits noradrenergic
reuptake(weak)
NDRI antidepressants buproprion-w ellbutrin inhibits dopamine reuptake(weak)
inhibits serotonin reuptake Serotoneric side effects: mental

ne
agitation, insomnia,anxiety,
panic attacks, akathisia,
psychomotoor restlessness,
mild parkinsonism, dystonia

inhibits norepinephrine reuptake sympathomimetic side effects:

blocks histamine
Abuse potential: antihistaminergic side effects:
weight gain, drowsiness;
epileptogenic

Dopamine>norepinephri
blocks M1 cholinergic receptor anticholinergic side effects:
constipation, blurred vision, dry
mouth, drowsiness, impaired
memory, psychomotor

ne
Tricyclic antidepressant a mitriptyline-e la vil impairment

 NOT FOR LONG TERM

29
 AGITATION 1
 PRESENTATION  CAUSES
 Violent,hostile,aggr
essive
 Danger to self or
staff
 Sexual acting
out,anger
 Self-limiting
 Reversible medical
causes
 Lack of impulse
control/ inhibition
 Premorbid
behavioral disorder
 Co-morbid TBI
associated behavior
disorder.
30
 AGITATION 2
 APPROACH
 R/O SECONDARY MEDICAL CAUSES
 METABOLIC, NEUROLOGICAL, PAIN
ADDRESS OTHER PREMORBID OR
COMORBID PSYCHO-COGNITIVE-
BEHAVIORAL DISORDERS
 NON-PHARM EMPHASIZED
 TABLE 5

31
 AGITATION 3
 NON-PHARM: ENVIRONMENT
 REDUCE LEVEL OF STIMULATION
 CONSISTENCY AND STRUCTURE TO
REDUCE CONFUSION
 PROTECT PT FROM HARMING SELF AND
OTHERS
 AVOID PHYSICAL RESTRAINTS

 TOLERATE RESTLESSNESS AS MUCH AS

POSSIBLE

32
AGITATION
DRUG CLASS EXAMPLES  Use other drug
MECHANISMS
OF ACT ION
ADVANT AGES

SEE SLEEP T ABLE classes first

5HT2A antagonist serotonin is a neurotransmitter
normally involved in sleep

Beware of drug
generation, less agitation and
 insomnia, anxiety S.E. than
other serotonergic agents; less

interactions
serotonin antagonist,/reuptake inhibitor trazadone -desyrel CV and anticholinerg
serotonin reuptake
inhibitor
anticholinergic relative dearth of anticholinergic
and CV S.E.

Beware of
antihistamine

beta antagonist Propranolol- inde ral effective general psychotropes

SEE ANXIET Y T ABLE

cognitive side
5HT1A agonist more specfic to anxiety than

effects
other serotoninergic
antidepressants, avoids BZD
serotonin 1A partial agonist Buspirone -buspar
side effects
blocks beta adrenergic treat associated sympathetic
receptors hyperarousal; social phobia
beta adrenergic antagonist Propranolol-inderal components
alprazolam-Xana x
 Neuroleptics and
opens GABA Cl-
channels,
inhibitory;cortical
rapid onset, reliable sedation

BZD as last resort

suppressant

for NEUROSTIMULAN
benzodiazepine

emergencies
SEE PSYCHOSIS T ABLE
dopamine antagoinst

TS-
typical antipsychotic haloperidol-haldol

SEE MOOD-DEPRESSION T ABLE

only
TCA amitiptyline-elavil Ritalin,bromocriptin
e
SEE MOOD-BIPOLAR T ABLE
??; 2nd messenger general mood stabilizing,
system antiagressive effect

classic lithium
MOOD
enhance inhibitory GABA
valproic acid- depakene
STABILIZERS –
actions; reduce excitatory
glutamate actions;

anticonvulsants carbamazepine-tegretol VALPROIC ACID less cognitive and motor side effec

SEE COGNIT IVE-NEUROST IMULANT S

T ABLE
ANXIOLYTIC – 33
MOOD- BIPOLAR DISORDER
1
 TYPES:  NEUROTRANSMIT
 MANIA AND TERS
HYPOMANIA  MONOAMINES
 DEPRESSION  Serotonin
 Dopamine
 Noradrenergic
 OTHERS
 Neurokinin
 Substance P

34
MOOD- BIPOLAR
DRUG CLASS EXAMPLES M ECHANISM OF ACT ION ADVANT AGES
ANTIDEPRESSANTS SEE DEPRESSION T ABLE

classic lithium ??; 2nd messenger system

ANTICONVULSANTS
va lproic a cid-de pa kote GABA-ergic

CLASSICAL
ca rbama ze pine -te gre tol inhibits uptake and release of norepi, less cognitive side effects than other
GABA-ergic anticonvulsants.
la motrigine -la micta l
ga ba pe ntin-ne urontin GABA-ergic
GABA-ergic topirima te -topa ma x
BENZODIAZEPINES dia ze pa m-valium
LITHIUM (2ND MESSENGER
 Y T ABLE
SEE ANXIET
SEE PSYCHOSIS T ABLE
SYSTEM)
ANTIPSYCHOTICS ha loperdol-haldol
AUGMENTING AGENT
Hormone thyroid
SEROTONIN 1A AUGMENTING AGENT
serotonin 1A partial agonist buspirone -buspa r Synergistic with SSRI
SEE DEPRESSION T ABLE ANTICONVULSANTS
MAOI/ TCA COMBO
HORMONE AS ANTIDEPRESSANT
AUGMENTER e stroge n +SSRI VALPROATE (gaba ?)
SEDATIVE-HYPNOTICS SEE SLEEP T ABLE
ANXIOLYTICS SEE ANXIET Y T ABLE

BIPOLAR COMBOS bipolar disorders ANXIOLYTICS

Combination treatment with 2 or more above psychotropic medications is the rule r

BUSPAR (serotonin 1A
agonist)
SEDATIVE-
HYPNOTICS
TRAZADONE (serotonin
2A antagonist-SRI)
ANTIPSYCHOTICS
SEROQUEL (dopamine35 2
 Blunt affect
Emotional
withdrawal
Delusions
Poor rapport
Hallucinatio
Passivity
ns
Apathy
Distortion in
Social
language
withdrawal
and
communicat
ion
Distorted
behavior
monitoring

46
Impaired attention,exec fx; psychosis
 PSYCHOSIS 1
 SCHIZOPHRENIA
 5 SYMPTOM DIMENSIONS
 THEORIES OF SCHIZOPHRENIA
 NEURODEVELOPMENTAL
 Abnormal degenerative process that begins
during fetal brain development.
 NEURODEGENERATIVE
 Progressive loss of neurons beginning in
young adulthood.
 DON’T CONFUSE WITH ATTENTION
DEFICIT 37
 PSYCHOSIS 2
 NEUROTRANSMITTERS
 DOPAMINE EXCESS
 GLUTAMATE EXCESS

38
49
PSYCHOSIS
CLASS/T YPE EXAM PLES M ECHANISM S OF ACT ION ADVANT AGES
CONVENTIONAL
ANTIPSYCHOTICS
dopamine antagonist halope ridol- ha ldol

blocks dopa mine

blocks M1 cholinergic

blocks histamine

blocks alpha 1 adrenergic

ATYPICAL ANTIPSYCHOTICS
dopamine-serotonin antagonist que tia pine - D2 blocka de better control of neg symptoms, lo
se roque l se rotonin a nta gonist EPS, less cognitive side effects
blocks histamine effective for depression
blocks M1 cholinergic associated with mania or
psychotic features.
blocks alpha 1 and 2 adrenergic
blocks serotonine reuptake
blocks norepinephrine reuptake

 Use atypical over

typical side effects
because of less
cognitive side effects
 No 2 antipsychotics 40
 OTHER
 MOTOR  BEHAVIOR
 TREMORS  EMOTIONAL
LABILITY
 AKASTHISIA
 HYPERPHAGIA
 SPASTICITY  APHASIA-
 ENDOCRINE bromocriptine
 SEXUAL  OTHER
DYSFUNCTION SYNDROMES
 METABOLIC  PTSD
DISORDER  OCD
 REWARD AND
ABUSE
41
52
 NEUROANATOMICAL
CORRELATES
 MULTIPLE NEUROTRANSMITTERS AND
PATHWAYS INVOLVED IN EVERY
PSYCHOBEHAVIORAL DISORDER, MANY
STILL UNKNOWN
 OUR LIMITED KNOWLEDGE OF THE
OVERALL PATHOPHYSIOLOGY OF
PSYCHOBEHAVIORAL DISORDERS IN BI
LIMITS OUR ABILITY TO MAKE
NEUROANATOMICAL CORRELATES
 CENTRIPETAL MODEL OF RECOVERY
 TREATMENT IS STILL BASED ON
SYMPTOMS AND CLINICAL PICTURE, NOT
ANATOMICAL LOCALIZATION.
43
 TAKE HOME POINTS
 THE BRAIN INJURY AFFECTS PSYCHO-
COGNITIVE-BEHAVIOR IN UNCLEAR
WAYS
 R/O SECONDARY CAUSES, NOT
NECESSARILY DUE TO BI ITSELF.
 FIRST DO NO HARM: SIDE EFFECTS,
DRUG INTERACTIONS
 NON-PHARM APPROACH FIRST.
 WE STILL TREAT PEOPLE NOT 44
 ACKNOWLEDGMENTS
 PSYCHOPHARMACOLOGY IN BRAIN INJURY
REHABILITATION
 37TH Comprehensive Review Course in Physical
Medicine and Rehabilitation. Feb 25, 2003.
Baylor College of Medicine.
 Sunil Kothari M.D.

 ESSENTIAL PSYCHOPHARMACOLOGY
 2nd Ed. Cambridge Press 2000
 Stephen Stahl

45
THANK YOU THAT’S ALL
FOLKS!

56
47
IETY- DEPRESSION CONTINUUM

46
 ANXIETY 2
 NEUROTRANSMITTERS
 GABA
 NORADRENERGIC

 SEROTONIN

49
ANXIETY
DRUG CLASS/T YPE EXAM PLES M ECHANISM OF ACT ION ADVANT AGES

ANTIDEPRESSANTS SEE DEPRESSION TABLE

Buspirone -buspa r serotonin 1A partial agonist; augments more specfic to anxiety
SSRI than other serotoninergic
antidepressants, avoids
serotonin 1A agonist,partial agonist,or
BZD side effects
antagonist
ANXIOLYTICS

a lpra zola m-Xa na x

ANTIDEPRESSANT-REMERON
opens GABA Cl- channels, inhibitory
rapid onset, reliable
sedation

(SSRI)
benzodiazepine

barbiturate
ANXIOLYTICS
meprobromate
ADJUNCTIVE TREATMENTS
GABA – VALIUM
blocks alpha 2 adrenergic receptor effective for anxiety w/
hyperadrenergic states
alpha 2 adrenergic agonist clonidine -ca ta pre s

(benzodiazepine),
blocks beta adrenergic receptors treat associated
sympathetic hyperarousal;
beta adrenergic antagonist Propra nolol-inde ra l social phobia components

NEW PROSPECTS
antihistamine

cck antagonist in clinical testing

PHENOBARBITAL (barbiturates) sedating

crf antagonist

NORADRENERGIC

CLONIDINE (alpha 2 agonist)

PROPRANOLOL (beta
antagonist)
Consider serotonergic
serotonergic
SEROTONERGIC
antidepresssants first to avoid side
BUSPAR (serotonin 1Apartial
effects of classical anxiolytics.
agonist)
Buspirone is a serotonergic agent
more specific for anxiety w/o the
side effects of other anxiolytics
50
 COGNITIVE- MEMORY 1
 CHOLINERGIC  SEEN IN:
DEFICIENCY  VARIOUS
HYPOTHESIS OF DEMENTIAS
AMNESIA  ALZHEIMER’S,
VASCULAR,
 NORMAL PRESSURE
HYDROCEPHALUS

51
 COGNITIVE-MEMORY 2
 NEUROTRANSMITTERS
 ACETYLCHOLINE

52
COGNIT IVE ENHANCERS/
M EMORY
EFFECT ON
CLASS TYPE EXAMPLES MECHANISM OF ACTION NT LEVELS ADVANTAGES
COGNITIVE ENHANCERS/ PROMESTIC
AGENTS
ACHE-I
donepezil- aricept
tacrine- cognex

rivastigmine- exelon
metrifonate
CHOLINERGIC PRECURSORS physostigmine
cholinergic precursors
choline
lecithin
CEREBRAL VASODILATORS
carbob monoxide
carbonic anhydrase
inhibitor
anticoagulants
nicotinic acid
pyritinol
meclofenate
vitamin E
yperbaric oxygen
papaverine
cyclandelate
isoxuprine
vincamine
cinnarizine

METABOLIC ENHANCERS
hydergine ??
VITAMINS AND HORMONES
B12
thiamine ACHE-I: ARICEPT
zinc
ginkgo biloba
chlation therapy ???, placebo effect

MOST UNPROVEN IN TBI

NOOTROPIC DRUGS

POP.
EXCESSIVE
UNACCEPTABLE PNS
SIDE EFFECTS
TABLE 3: 53
EYE,CV,GI,LUNG,GU,ETC.