1. PSYCHOPHARMACOLOGY
ANTI-PSYCHOTICS
ANTI-SCHIZOPHRENICS
Psychiatric Illness
Impairment of thinking process, mood, behavior and perception
Psychiatric Illness:-
Neurosis: Psychosis
 Mild Problem serve problem
Comprehension to accept reality that he is ill and exaggerate his condition. Patient
lives in imagination
Neurosis include anxiety states
 Anxiety
 Phobic states: fear of places, persons or situations
 Obsessive compulsive states even can’t stop himself voluntary, he compel to do it.
 Post traumatic stress disorder
 Hysteria: having severe physical sufferings, Rxn in response to severe disease, loss
of some relative or some hard situation etc.
 Reactive depression.
Psychosis:
 Schizophrenia
Split mind
Thought disorder
 Affective disorders
Depression
Mania
Bipolar depressive illness
 Organic Psychosis
Mentally disturb caused by
Alcoholism
Org - disease
Head injure
Schizophrenia:
 Most important and highly disabling
 Large portion of patients in mental hospitals
 Affect in early young adult life
Incidence:
 1 % of total population

2.  Ac episode ____ 20 % cured by treatment
 Rest follows a chronic cause
 Suicide is about 10% cases
Etiology:
 Not known
 Strong but incomplete genetic pre-disposition
 (1st degree relatives – 10%)
 (2nd monozygotic twin – 50%)
Genetic predisposition but not complete.
Hypothesis:
1. Environmental Factors:
Maternal viral infection associated with autoimmune process & high B.P during
pregnancy
2. Neurodevelopmental Factors:
Involving mainly cerebral, cortical neurons & limbic system
Symptoms:
1.Positive symptom: (result from Neurochemical Abnormality)
Increase do paminergic transmission Respond well to Rx
a) Delusions often paranoid in nature:
(persecuting type pt. feeling everybody conspirating against him, laughing at them) in
nature.
These delusions cant be rectified by reasoning.
b) Hallucinations:
(usually auditory often exhortatory in their message)
They may be
• Visual
• Auditory
• Tactile (CD Canine bugs)
Usually threatening, harsh types and pt. responding to those hallucinations.
c) Thought disorder
Wild train of thoughts and garbled sentences.
 Draw irrational conclusion with the feeling that thoughts are inserted or
withdrawn by an outside agency.
 Usually not like to be interfered, flight of ideas from one thought to other thought.
 Broadcast of ideas.
d) Abnormal stereotypical behavior, usually aggressive.

3. e) Defectiveness in selective attention unnecessary voices are ignored but he can’t
ignore unnecessary voices.
2. Negative Symptoms:
• Result from brain atrophy
• Don’t respond / less responsive to Rx
a) Emotional blunting (flattening of emotional responses) he likes to remain alone.
b) Poor Socialization (withdrawal of social contacts)
c) Cognitive deficit (Dementia)
Irritability more irritable.
Neurochemical Basis:
1) Dopamine Theory (Hypothesis by Carlson awarded noble prize in year 2000)
Dopamine hyperactivity in mesolimbic and mesocortical pathway & amygdale
positive symptoms of schizophrenia.
Proof:
• Dopamine agonists – produce these symptoms of schizophrenia e.g. central
sympatholytics Amphetamines)
• Block Dopamine recap Improve the symptoms
2) Glutamate Theory
 Glutamate and DA exert excitatory and inhibitory effects respectively on
GABA ergic striatal neurons which project to thalamus and constitute
“sensory Gate”
 Glutamate or DA disables the gate and uninhibited sensory input
reaches the cortex.
 Glutamate NMDA (N-methyl deaspartate) recep antagonists:
Phencyclidine
Katamine Produce Psychotic Symtoms
Dizoclipine
3) 5 – HT Theories:
• 5 – HT dysfxn
• LSD & 5-HT2 Receptors agonists produced schizophrenia like syndrome.
Mostly of Anti-psychotics in addition to affect dopamine also back serotonin
receptors.
4) Current views:
Combination of DA hyperactivity with 5-HT & glutamate dysfxn.
DA – Recognized as NT 1959

4. 1) Nigrostriatal Pathway:
 75% of dopamine in brain
 Co-ordination of motor movements activity: Parkinsonism activity
auntingtons chorea
2) Mesolimbic mesocortical pathway:
 Projects from neurons near S.N to limbic system & Neocortex
 Behaviorial effects
 Hyperactivity leads to schizophrenia.
3) Tuberoinfundibular (Tubrohypophy Scal) Pathway:
Connects arcuate nuclei & prevent nuclei hypothalamus and post pituitary.
Regulation endocrine control – control MSH, GH, Prolactin.
4) Medullary Perventricular Pathway:
 From neurons of Motor Nucleus of Vagus ___ Periventricular nuclei
 Eating behavior
Satiety center ____ Bolimia Nervosa
Appetite Cetre _____ Anorexiz Nervosa
5) Incertohypothalamic Pathway:
 From medial zone incerta to hypothalamus & Amygdala.
 Sexual drive, Microvasculatory function and temperature regulation.
6) Many local Dopaminergic Neurons in olfactory cortex & retina:
7) Dopaminergic transmission in periphery:
- Renal Vasculatory
- Mesenteric pathway
- CVS
DOPAMINE TRANSMISSION INVOLVED:
a- Motor Effect:
Deficient in nigrastriatal system ___ Parkinsonism Excess of DA ___ Huntigton
b- Behavior Effect:
DA hyperactivity in mesolimbic & mesocortex pathway ___ schizophrenia
c- Endocrine Effects:
i) Agonists (Ergot & Non-Ergot)
Decrease in Prolactin & MSH
Increase in GH (in N individuals, in acromegaly patients opposite effects)

5. ii) Antagonists (Anti-Psychotics)
Increase in prolactin ____ Infertility
d- CTZ & Vomiting:
Stimulated
DA Receptors & Their Location:
D1 Family:
 Increase in CAMP
 Increase in PIP2 hydrolysis
 Cat2 mobilization
 PKc activation
Distribution:
D1
 Striatum
 Neocortex
 Nucleus accustoms
 Olfactory tubercle
 Periphery
Fxn:
1. CNS
2. Horizontal cell coupling in retina
3. Dilation or renal & mesentreric
4. Increase in force of myocardial contraction
DS:
 Hippocampus
 Hypothalamus
D2 Family: (D2, D3 & D4)
 Decrease in CAMP Post Synaptic
 Increase in K conductance
 Decrease in voltage gated Cat2 currents (pre-synaptic)
Distribution:
D2
 Striatum (caudate & Putamen)
 Substantia nigra pars compacta (SNPC) ____ Pre & post synaptic inhibition
 Olfactory Tubercle
 Nucleus accumbans
 Pituitary

6. D3
 Olfactory tubercle
 Nucleus accumbanes
 Hypothalamus
 Frontal cortex & medulla & mid brain
D4
 Frontal Cortex
 Medulla
 Mid brain
PSYCHOTROPIC DRUGS:
Drugs which effect mood & behavior.
1) Anxiolytics, sedatives, hypnotics, Minor tranquillizers: (Psychorelaxants):
Reduce anxiety and induce sleep
2) (Anti-psychotics, Anti-Schizophrenics, Major tranquillizers, psycholeptic,
ataractic) Neuroleptics: ___ Neuron seize
Seize those neurons which are hyperactive
effectively relieve symptoms of schizophrenia.
3) (Thymoleptics, psychoenergisers) Anti-depressants:
 Depress depressive idealization
 No Anti-depressant is CNS stimulant
 Alleviate symptoms of depressive illness.
4) Psychomotor stimulants (Psychostimulants)
 Cause wakefulness & Euphoria
5) Psychodysleptics, psychotomumetic, psychedelics: (Hallucinogens)
Cause disturbance of perception & behavior _____ Psychosis like illness.
6) Antimaniacs (Mood Stabalizers)
Control mania
7) Neurotropic drugs:
Enhance mental performance
NEUROLEPTICS
(ANTI-PSYCHOTICS)
A) Classical Typical Nemoleptics:
1. Phenothiazines:
a) Aliphatic Comp:
 Chloropromazine (Largactil)
 Promazine
 Triflupromazine

7.  Promethazine (Phanergen)---got important anti-histaminic actions,
so, commonly placed in H1 blockers
Chlorpromazine: discovered by surgeon, trying to find that relief
person in surgery.
b) Piperidine Derivative:
 Thioridazine (Melleril) Polent Anti-Cholinergic
 Mesoridazine (metabolite of thioridazine) Action
 Mepozine
 Piperacetazine
 All Anti-psychotics cause parkinsonism by blocking DA receptors
in Nigrostriatal system so drug having Anti-muscarinic effect
neutralize this effect.
c) Piperazine Derivative:
 Fluphenazine (I/V preparation, slowly, release,
 Perphenazine Adv.
 Trifluperazine 1) Long DOA
 Prochlorperazine 2) Patient Compliance becomes
 Thioperazine better as in schizophrenia.
 Acctophenazine
 Carphenzaine
So, to overcome compliance problem as schizophrenia patients never
accept that he is sick, so longer acting DEPOT Preparation made to over
come this problem.
DEPOT preparation ____ slowly release
2. Thioxanthines: (also available as DEPOT preparation)
 Thiothixene
 Clopenthixol ___ inj. ____ for false thoughts
 Flupenthixol
 Zuclopenthixol
 Chlorprothixine
3. Butyrophenones:
 Haloperiodol
 Properidol
 Benperidol
 Triflupeidol
4. Rauwalfia alkaloids:

8. Reserpine ___ useful as deplete DA
___ Not used as induce suicidal thoughts
None of alkaloids are used now-a-days.
B) Atypical Neuroleptics:
Their mechanism of action is different from anti-psychotics
 Loxapine
 Clozapoine (Clozanl) ___ A/E: Cause agranulocyctosis ___ Bone marrow
depression
 Risperidone ____ commonly used D2 5HT2 selective activity for D4
receptors
 Olanzapine __ Disadv: cause agranulocytosis
 Ziprasidone
Treatment patients who are resistant to other drugs. Also R x of negative
effects
 Sulpirdie (D2 selective)
 Remazopride
 Remoxipride
 Primozide (D2 selective) long acting indole
 Quetiapine
 Aripiprazole (partial agonist at D & SHT a antagonist at x