Introduction –

CNS pharmacology
-Drugs

-Terminology – Key words

-Neurotransmitters
 Drugs for -------
Neurological diseases For other
purposes

-Sleep disorders General

-Parkinson anesthetics
-Seizure disorders
-Alzheimer For sedation
-Behavioral
CNS depression
Sedation
Drowsiness
Sleep - Deep sleep
Delirium
Anesthesia
Stupor
Semi coma
Coma
Death
-General anesthetics
-Sedative hypnotics

-Narcotic analgesics
-Nonnarcotics
(analgesics) (NSAIDs)
-Alcohols
-Anti-seizure drugs
[Epilepsy]

-Neurodegenerative diseases
-Parkinson
-Alzheimer
-Drugs of Abuse

-Psychedelic drugs
(mind revealing drugs)

-CNS stimulants
Feeling
-Psychological disorders

[Behavioral disorders]
-limbic system – amines
 Psychopharmacology
Increased amines

Elation – BIPOLAR
PSYCHOSIS
DISORDER
SCHIZOPHRENIA

Decreased amines
ANXIETY STATES
DEPRESSIVE
DISORDERS
 Psychopharmacology
Increased amines
Elation – BIPOLAR DISORDER
PSYCHOSIS
SCHIZOPHRENIA Mood stabilizers and
Antipsychotics for acute
ANTIPSYCHOTICS phase
BLOCK DA,5HT receptors
Decreased amines
ANXIETY STATES
DEPRESSIVE DISORDERS
Antianxiety medications
Antidepressants:
POTENTIATE AMINES, NE,
DA, 5HT mainly by inhibiting
the reuptake
 Schizophrenia Bipolar disorder
1st degree relative 10% 20%
(sibling, DZ, or
parent) of a
patient
Child of two 40% 60%
parents with the
disorder
MZ twin of a 50% 75%
patient
Genetic basis LA: 5,11,18,22; SA: Chromosome 12, 18
19, (6:dysbindin (earlier:
gene) (8:neureregulin chromosome 11)
1 gene) (13:
glutamate
transmission gene)
 Dopaminergic tracts in brain.1

Nigro- Muscle Less dopamine Levodopa

striatal tone, Parkinson 
tract move- disease dopamine
ment
Tubero Decreases DA blockade DA
infundi- prolactin Increased agonists
bular prolactin,
tract galactorrhea,
(PIF) sexual
dysfunction
 Dopaminergic tracts in brain.2

MesoLimbic Positive symptoms Older

Mesocortical Negative symptoms Atypical
(Psychosis) (antipsychotics)
Ventral teg- Reward, positive
mental area to reinforcement to take
Nucleus the drug – substance
accumbens abuse
NAC pathway
IMBALANCE Ach-DA-
PARKINSON
 LESS DA
 MORE ACH

 SYMPTOMATIC ADJUNT USE OF

anticholinergics – ATROPINE and atropine
substitutes like benzhexol
(trihexyphenidyl), benztropine, cycrimine,
procyclidine, biperiden
 Basal ganglia
Extrapyramidal fibers
Imbalance
Less DA – more Ach

Extrapyramidal symptoms
Parkinson
Dystonia
Akathisia
Tardive dyskinesia
Drugs that induce Parkinsonism
 BUTYROPHENONES: haloperidol, droperidol
 Phenothiazines: (antipsychotics) chlorpromazine
 D2 antagonists: antiemetics: metoclopramide,
domperidone
 Central alpha2 agonists: Alpha methyl dopa,
clonidine
 Catecholamine depletor: reserpine
 Adrenergic neurone blocker: guanethidine
 Cerebellum

- middle ear  vestibular apparatus 

CTZ – area postrema – vomiting center

Motion sickness
Frontal lobes
Dorsolateral Executive Amotivation, loss of
convexity function conc, attention,
disorientation, mood
disturbances
Orbitofrontal Biological Disinhibition, loss of
cortex drives judgment, pseudo-
psychopathic
behavior
Medial cortex Movement Apathy, akinesia,
control gait disturbances,
incontinence
Temporal lobes – medial temporal lobe –
New learning impaired – short-term, long-
term memory spared
Memory Impaired memory
Learning and learning,
inability to
Emotion
understand language
Auditory processing (Wernicke’s aphasia
– left sided lesions),
changes in behavior
Parietal lobes
Somatic sensation and Impaired IQ
body image Impaired info processing
(visual-spatial info)
Gerstmann syndrome
(left sided lesions)
Occipital lobes

 Vision

 Visual hallucinations, illusions

 Blindness
Limbic lobes
Hippocampus Memory Poor new
storage learning, short-
term memory
spared, but
long-term
impaired
Amygdala Coordination of Kluver-Bucy
(dorsomedial emotions with Syndrome
part of temporal somatic
lobe) responses -
anger-
aggression
Neurotransmitters
GABA-GLUTAMATE SYSTEM
GABA – inhibitory –
Sedative hypnotics (benzodiazepines,
nonbenzodiazepines, barbiturates), general
anesthetics, alcohol
Dopamine (DA), Acetylcholine (Ach)
Norepinephrine (NE)
5 hydroxytryptamine (5HT)
 Receptor concept
Cholinergic – muscarinic – G protein coupled
Cholinergic – nicotinic – direct – no second
messenger system - Na/K
GABA – chloride ion channels
Glutamic acid – NMDA (N-methyl D-aspartate), AMPA
(alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) , Kainate
– cation channels – Ca++
Glycine – chloride channels
DA, NE, 5HT – C AMP
Opioid – G protein – adenylyl cyclase
 5-HT (tryptophan derivative)
 Dorsal raphe nucleus in the upper pons and lower
midbrain- Mood, sleep, pain, appetite, sexuality, impulse
control
 Increased 5-HT: positive effects like - improved mood
and sleep; negative effects like delayed orgasm;
psychotic symptoms in high conc: newer antipsychotics
have 5HT blocking effects
 Decreased 5-HT: mood depression, poor impulse
control, SUICIDE, violent behavior, alcoholism,
chronic pain syndrome, sleep disorders, anxiety
disorders like OCD – antidepressants, SSRI, SSNRI
Histamine (ethyl-amine)
 Sedation, sleep, mood, appetite

 BLOCKADE OF HISTAMINE RECEPTORS (H1)

 MORE SLEEP
 MORE APPETITE ----- weight gain
Quaternary amine - Ach

 Loss of cholinergic neurons -Decreased Ach -

Decreased choline acetyl transferase (required
for Ach synthesis) (choline + acetylCoA) 
Alzheimer  Dementia (hippocampus),
Down’s syndrome, movement disorders, sleep
disorders ------- Alzheimer – anticholinesterase
drugs to increase Ach – Donepezil, Tacrine,
Rivastigmine, galanthamine
 Biochemistry of behavior
Neurotransmitters
1 Biogenic amines (Monoamines): Pre-
synaptic terminals (catecholamines – DA,
NE) (indolamines – 5HT), (ethylamines –
Histamine), (Quaternary amines - Ach)
2 Amino acids: Pre-synaptic terminals
3 Peptides: neuronal cell bodies
Second messengers

cyclic adenosine -
monophosphate(cAMP),
guanosine monophosphate(cGMP);
lipids-diacylglycerol (DAG),
Calcium
 Dopamine (DA)
 DOPAMINE HYPOTHESIS – AMINE
HYPOTHESIS – amines produce elation / mood
elevation / mania / psychosis
 SO BLOCK AMINE TRANSMISSION /
RECEPTORS
D2 blockers: Traditional antipsychotics/
neuroleptics: chlorpromazine, haloperidol
Newer/atypical antipsychotics block D1,
D4: clozapine- ALSO 5 HT
DA
 Nigrostriatal pathway-LESS DA –
parkinson- EXTRAPYRAMIDAL EFFECTS
 Meso-limbic-cortical pathway- EXCESS
DA – psychosis- POSITIVE SYMPTOMS
 Tubulo-infundibular pathway – DA IS PIF,
so less DA – LESS PIF – means more
prolactin
 NAC PATHWAY – ADDICTION
PATHWAY
Nor-epinephrine (NE)
Heart, Bronchus, BP
 Nuclei in the upper brainstem – Locus
ceruleus
 Mood, anxiety, arousal, learning, memory
 LESS NE  DEPRESSION
 EXCESS NE (and 5HT)  MANIA
Muscarinic receptors

 Behavior
 Adverse effects of psychoactive agents
 Muscarinic blockade by antipsychotics, TCAs
– Blurred vision, constipation, urinary
retention/hesitancy, dryness of mouth
Amino acids
 GABA – inhibitory neurotransmitter –decreased
GABA  Anxiety:
 GABA agonists – BZD, barbiturates – chloride ion
entry – decrease anxiety
 Glycine – inhibitory neurotransmitter – spinal cord –
regulates excitatory Glutamate
 Glutamate  epilepsy, neurodegenerative illnesses,
memory formation, mechanisms of cell death
 Schizophrenia  disruption of NMDA pathway
Neuropeptides..1

 Endogenous opioids
 ENKEPHALINS, ENDORPHINS
 Relieve pain, anxiety
 Also play role in addiction and mood

 Placebo effects: opioids, DA

 Neuropeptides ..2
CCK, neurotensin Schizophrenia
Somatostatin, Mood disorders
substance P,
vasopressin, oxytocin,
VIP
Somatostatin, subst P Huntington
Somatostatin, VIP Alzheimer dementia
Substance P, CCK Anxiety disorders
Substance P Pain, aggression
metabolites
 NE 
MHPG (3-methoxy-4-hydroxy-phenyl-
glycol)Pheochromocytoma-VMA

 DA 
HVA (Homovanillic acid)

 5-HT 
5-HIAA (5-Hydroxy-indol-acetic acid)
Depression Decreased Left prefrontal Limbic
NE(MHPG) cortex system
5HT,
DA(HVA)

Mania Increased DA Right Limbic

(HVA) prefrontal system
cortex

Psychosis Increased Bilateral Limbic

DA(HVA), prefrontal system
5HT(5HIAA), cortex
glutamate
Anxiety Decreased Locus Right
GABA, ceruleus para-
5HT(5HIAA) hippo
Increased campal
NE(MHPG) gyrus

Dementia Decreased Hippo Nucleus

Ach campus basalis
Increased of
Glutamate Meynert
Neurological
-Broca’s area – Language
Prefrontal cortex-personality functions
Dorsolateral convexity-EXECUTIVE
Conc, attention, plan, problem-solving
Left – speech, writing, reading
Right – perception, spatial, immage,
puzzle-solving, music, art, literature
Temporal-memory, learning, language-
auditory processing
hemispheres
Left Right
Larger in size Smaller in size
Information Information
processing faster processing slower
Calculation type Intuition type
problem solving problem solving
Damage: Damage: apathy
depression and indifference
Language Perception, artistic,
visual-spatial,
prosody
Temporal cortex –
language, memory, emotion

Parietal cortex-
info processing left-verbal, right-visual-spatial

Occipital cortex –
visual inputs, recall of objects scenes distances
 Genetics and behavior
-Family risk studies – to distinguish
between genetic and other risk factors
-Proband: index case: affected individual from
a family – study the relatives of a proband
-High concordance rate in close relatives
indicates genetic component involved. E.g
responsiveness to stimuli, fearfulness, activity
level, distractibility
-Twin studies
-schizophrenia, bipolar disorder
Personality disorders
Cluster A Cluster B disorders Cluster C
disorders Histrionic Avoidant
Schizoid Narcissistic Obsessive-
Schizotypal Antisocial compulsive
Paranoid Borderline Dependent

Schizophrenia Major depression Anxiety

in relatives Substance abuse disorders In
disorders relatives
In relatives
Neuropsychiatric disorder - Alzheimer
 25 to 50% of close relatives of Alzheimer
patients eventually develop the disease
 Higher concordance rate in MZ > DZ
 CHROMOSOME 21- Down’s syndrome-
trisomy 21 living beyond 40 develop
behavioral and neuroanatomic features of
Alzheimer
 Apolipoprotein E2 allele on chr 19 –
decreased risk
 Apolipoprotein E4 allele on chr 19 –
increased risk esp in women
Hunginton, Tourette, substance abuse
 Huntington – fatal AD disorder –abnormal gene
on short end of chr 4 – offspring of 1 affected
parent has 50% chance
 Tourette – higher concordance rate in MZ > DZ
 Substance abuse
 – alcoholism – twice in MZ; adopted children
show characteristics of biological parents; 4
times more prevalent in biological children of
alcoholics; Sons > daughters; esp before 20s
 -Cocaine: polymorphism in the promoter region
of prodynorphin gene – protection against
cocaine abuse
Behavioral neuroanatomy

 Brain: cerebral hemispheres, basal

ganglia, thalamus
 Brainstem: Pons, medulla, midbrain
 Spinal cord
 Cerebral cortex
Sensory, motor, association areas
Frontal, temporal, parietal, occipital
lobes, limbic lobes (medial parts of
frontal, temporal, parietal lobes)
 Frontal lobes – 4 subdivisions
 1 motor strip2 supplemental motor area:
motor behavior
 3 Broca’s area: language
 4 prefrontal cortex: personality functions
 Prefrontal lobe syndrome/frontal
release signs
 Perseveration, repeated unnecessary
behavior and thought, dysinhibition,
sudden outbursts of temper, regression to
infantile reflexes
 schizophrenia, OCD: personality, affect
(decreased bilateral prefrontal cortical
activity on fMRI (functional magnetic
resonance imaging) and positron emission
tomography (PET scan)
Prefrontal cortex – 3 subdivisions
 Orbitofrontal region: Center for biologic
control of inhibition, emotion, drive, DA
driven “reward circuit” – positive
reinforcement – substance abuse (nucleus
accumbens) (NAC pathway)
 Dorsolateral convexity: behavior and
personality: “EXECUTIVE”: formulation of
plans, attention, concentration, problem
solving strategies, mood
 Medial region: Motor activity
Frontal cortex

 Emotional and behavior functions are

lateralized
 Lesions of LEFT prefrontal area- cortical,
subcortical - lead to DEPRESSION –
stimulation of the area leads to positive mood
 Lesions of RIGHT – lead to ELEVATED
MOOD: stimulation leads to stress
Limbic lobe/system - emotions
 Hypothalamus  cerebral cortex 
autonomic
 PAPEZ 1937 – PAPEZ CIRCUIT  anterior
nucleus of thalamus  cingulate gyrus 
amygdala  hippocampus  mamillary
body fornix  thalamus
 Lesions of Amygdala, hippocampus 
behavioral abnormalities
 Volume of these is reduced in Schizophrenia
Basal ganglia – parkinson, huntington,
tourette
 Receive info from entire cortex  project it
to frontal lobes via thalamus
 Corpus striatum (caudate N, putamen)
 Globus pallidus
 Substantia nigra
 Subthalamic nucleus
 Desire execute movement
Communication betwn hemispheres

 Corpus callosum
 Anterior commissure
 Hippocampal commissure
 Habenular commissure
Left – dominant right - nondominant
 Left – language function – speech, writing, reading
 Right – perception, spatial relations, body
image, recognition of faces and music,
puzzle-solving, map-reading, musical, artistic
abilities – (damage  motor sequelae, indirect
effects on behavior; no effect on intelligence or
personality)
 Women larger corpus callosum and anterior
commissure; women use both hemispheres for
verbal tasks; men better developed right
hemisphere  spatial tasks
Consciousness, arousal, coma,
death
 Thalamus – also pain, reticular formation
( a network in brainstem)
 Brainstem  thalamus (coma)
 Level of consciousness (Glasgow Coma
Scale 3 to 15)
 Profound coma (no cognitive function) 
persistent vegetative stage
PNS – sensory, motor, autonomic including spinal nerves,
cranial nerves, peripheral ganglia

 ANS - sympathetic, parasympathetic

 Hypothalamus – betn thalamus and
pituitary – biological control of emotions,
temperature, drinking and eating behavior,
sexual activity
 Damage to Ventromedial nucleus (satiety
center)  increased appetite
 Damage to lateral nucleus  decreased
appetite
hemispheres
Left Right
Larger in size Smaller in size
Information Information
processing faster processing slower
Calculation type Intuition type
problem solving problem solving
Damage: Damage: apathy
depression and indifference
Language Perception, artistic,
visual-spatial,
prosody
Frontal cortex
 Speech, abstract thought, memory, higher
mental functions, concentration, personality
development
 Affection of frontal lobe: Perseveration:
meaningless repetition of acts, words,
constructions
 – Mammmaa, Mammaa, Mammaa
 -- Original Patient
lesions
Dorsal prefrontal cortex Orbitomedial frontal
cortex
-Apathy and reduced -Withdrawal
initiative, reduced attention -Fearfulness
-Poor grooming -Dysinhibitions (loss of
-Inability for abstract inhibitions 
thinking -Mood explosions and
-Broca aphasia violent outbursts
Temporal cortex – Stroke, tumor, trauma, herpes virus,,
language, memory, dementia (bilateral)/ Left: euphoria,
delusions, hallu, thought, verbal
emotion
comprehension loss/ Right: dysphoria,
irritability, decreased visual and musical
abilities
Parietal cortex- info Left: Gerstmann syndrome: agraphia,
processing left acalculia, finger agnosia, right-left
disorientation, learning, dementia
verbal, right visual-
Right: anosognosia, construction apraxia
spatial
(difficulty outlining objects),
Hemineglect/hemi-inattention (neglect of
opposite side !)
Occipital cortex – Cortical blindness
visual inputs, recall Anton syndrome: (bilateral posterior
of objects scenes cerebral arteries): cortical blindness,
denial of blindness
distances
 Nondominant (right) parietal lobe
 Constructional Original Patient
apraxia:
 difficulty
outlining
objects
Right parietal lobe
 Hemi-neglect Original Patient
or
 Hemi-
inattention
Motor mechanism of articulated speech

 Broca’s center = Broadmann area 44 –

posterior part of inferior frontal gyrus of the
left (dominant) hemisphere
 Broca’s aphasia = telegraphic,
ungrammatical speech
 = students class bored sleep afternoon
= students in the class were bored and
were sleeping in the afternoon !!!
 No loss of comprehension
Wernicke’s aphasia

 Superior temporal gyrus – Broadmann

area 22
 Comprehensive impairment
 Incoherent speech, verbal paraphasias
 Rapid speech hyperactivity
Amygdala – dorsomedial part of temporal
lobe
 ? Unconscious mind
 Kluver-Bucy syndrome: No fear, “Love”,
taming effect,

 Korsakoff syndrome: amnesia due to

chronic thiamine deficiency, alcohol, can
progress to thalamic damage
Memory

 Medial temporal lobe – impaired new

learning but both recent and remote
memory is spared

 Hippocampus – Impaired new learning,

spared recent memory, but remote
memory is impaired
 Basal ganglia
 Parkinson: substantia nigra, cogwheel rigidity,
shuffling gait, mask face, pill rolling, resting tremor,
bradykinesia, may davp dementia
 Huntington chorea: AD chromosome 4
choreoathetoid movements and dementia, onset 30-
40, progression to psychosis to infantile state, life
another 15-20 years, suicide common
 Wilson disease: AR, chromosome 13q, ceruloplasmin
deficiency, Cu meta, Kayser-Fleischer rings,
dementia, liver cirrhosis
 Calcification of basal ganglia – Fahr disease –
resembles schizophrenia with negative symptoms
Pick disease Creutzfeldt-Jakob
disease
Frontal and parietal lobes Prions
VERY RARE Onset 40-50
Fatal Fatal in 2 years
Personality change Vague complaints,
Cerebral degeneration, anxiety, ataxia,
dementia choreoathetosis,
dementia,
cortical/cerebellar
atrophy, no treatment
Other more common dementias
 Primary degenerative dementia of Alzheimer
type (DAT) – PROGRESSIVE ONSET –
Females – general deterioration
 Mostly > 65 YEARS – diffuse brain atrophy,
enlarged ventricles – donepezil, tacrine

 Vascular dementia – multi-infarct type – QUICK

ONSET- Males- patchy deterioration – (CVA) –
earlier ONSET than DAT – (HTN, DM),
HYPERLIPIDEMIA
Delirium Dementia Depression
Consciousness No No
impaired/clouded
Quick onset Slow onset - Slow onset
alzheimer
Stupor or agitation Normal Normal arousal
arousal
Illusions, delusions or Uncommon uncommon
hallucinations
Reversible Rarely Antidepressant
reversible treatment
Impaired Loss of Sad mood
consciousness intellectual
ability