This document discusses neuropsychiatry and antipsychotic medications. It begins by outlining the four dopamine pathways relevant to antipsychotic pharmacology: mesolimbic, mesocortical, nigrostriatal, and tuberoinfundibular. It then describes each pathway's anatomy, physiology, and implications for symptoms of schizophrenia. The document also covers types of antipsychotics, their mechanisms of action, indications, and various adverse effects including weight gain, sedation, and neurological side effects. In summary, it provides an overview of the neurobiology underpinning antipsychotic treatment and the therapeutic and adverse impacts of blocking different dopamine pathways in the brain.

1. NEUROPSYCHIATRY AND
ANTIPSYCHOTICS
By
EkamEmefiele
(Med. Student)

4. Dopamine pathways relevant to antipsychotic
pharmacology in the treatment of schizophrenia are:
 Mesolimbic pathway
 Mesocortical pathway
 Nigrostriatal pathway
 Tuberoinfundibular pathway
By blocking these pathways, antipsychotics can produce
both therapeutic and adverse effects.

5. Mesolimbic Pathway
This is relevant to positive symptoms of
schizophrenia (delusion and hallucination)
Anatomy: it is made up of projections from the
ventral tegmental area (VTA) to the nucleus
accumbens.
Physiology: it is the centre for motivation,
emotions, pleasure, compulsion.
Implication: D2 antagonism reduces positive
symptoms of schizophrenia

6. Mesocortical Pathway
Anatomy: This tract is made up of dopaminergic
neurons that projects from the VTA to the pre-frontal
cortex.
Physiology: it is relevant to the physiology of
cognition, negative symptoms, emotions and affects.
Implications: Hypofunction of this pathway might be
related to cognitive and negative symptoms of
schizophrenia

7. Nigrostriatal Pathway
This tract contains about 80% of the brain’s dopamine
Anatomy: It projects from the substantia nigra to basal
ganglia.
Physiology: It plays a key role in regulating movements.
Implication: D2 antagonism of this tract induces
extrapyramidal symptoms (pseudo-parkinsonism, akathisia,
acute dystonia) and Tardive dyskinesia (abnormal writhing
movement of the tongue, face and body).

8. Tuberoinfundibular Pathway
This pathway influences prolactin release.
Anatomy: This tract projects from the hypothalamus to
the anterior pituitary.
Physiology: Dopamine tonically inhibits prolactin
Implication: D2 antagonism increases prolactin level

9. Antipsychotics

10. Psychosis
Psychosis is a thought disorder characterized by
disturbances of reality and perception, impaired
cognitive functioning, and inappropriate or diminished
affect (mood).
Psychosis denotes many mental disorders.
Schizophrenia is a particular kind of psychosis
characterized mainly by a clear sensorium but a marked
thinking disturbance.

11. Substances that can induce psychotic
symptom
These includes;
 Alcohol
 Cannabis (Marijuana)
 Cocaine
 Amphetamines
 L. dopa

12. Schizophrenia
• It is a thought disorder.
• The disorder is characterized by a divorcement from
reality in the mind of the person (psychosis).
• Pathogenesis is unknown.
• Onset of schizophrenia is in the late teens early
twenties.
• Genetic predisposition -- Familial incidence.
• Multiple genes are involved.
• Afflicts 1% of the population worldwide.
• May or may not be present with anatomical changes

13. Symptoms
Positive Symptoms :
Hallucinations, delusions, paranoia, excited motor
behaviour.
Negative Symptoms :
Slow thought or speech, social withdrawal, emotional
blunting, cognitive deficits, extreme inattentiveness or
lack of motivation to interact with the environment.

14. Antipsychotic Medications (APMs)
 Used to treat manifestations of psychosis and other
psychiatry disorders
 Precise mechanism of action is unknown, however
APMs blocks several populations of dopamine (D2,
D4) receptors in the brain.
 The newer APMs also block serotonin (5-HT2)
receptors, a property that may be associated with
increased efficacy.
 APMs also variably blocks central and peripheral
cholinergic, histamine and alpha receptors

15. Classification of antipsychotic
drugs• PHARMACOLOGICAL CLASSIFICATION
– FIRST-GENERATION ANTIPSYCHOTIC (low potency)
• Chlorpromazine
• Prochlorperazine
• Thioridazine
– FIRST-GENERATION ANTIPSYCHOTIC (high potency)
• Fluphenazine (Modecate)
• Haloperidol (Haldol)
• Pimozide
• Thiothixene
• Zuclopenthixol (Clopixol)

16. – SECOND GENERATION ANTIPSYCHOTIC
• Aripiprazole • Asenapine
• Clozapine • Iloperidone
• Lurasidone • Olanzapine
• Quetiapine • Paliperidone
• Risperidone • Ziprasidone

17. Division of APMs based on receptor
blockade
There are three (3) main groups;
 Pure D2 antagonist: Typical APMs (low and high
potency).
 D2-5HT2 antagonist: Risperidone
 Multireceptor antagonist:
a. Clozapine - D2, D4, 5HT2
b. Olanzapine - D2, D4, 5HT2
c. Quetiapine - D2, D4, 5HT2
d. Ziprasidone - D2, D4, 5HT2
e. Aripiprazole - D2, D4, 5HT2

18. Typical versus Atypical APMs
Typical
• Older agents
• Dopamine effects
• Many side effects
• Treatment of positive
symptoms
Atypical
• Newer agents
• Dopamine and serotonin
effects
• Fewer side effects
• Treatment of positive
and negative symptoms

19. Indications for APMs
 Psychomotor agitation
 Schizophrenia
 Other psychotic disorders – delusional, brief
psychotic, schizophreniform, schizoaffective,
substance-induced psychotic disorders
 Mood disorders – useful for the treatment of agitation
and psychosis during mood episode.

20. General Adverse effects of APMs
 Weight gain (olanzapine)
 Sedation – due to antihistamine activity
 Hypotension – effect is due to alpha adrenergic
blockade. It is most common with low potency APMs
 Anticholinergic symptoms – dry mouth, blurred
vision, urinary retention, constipation, etc
 Endocrine effects – gynecomastia, galactorrhea,
amenorrhea, due to blockade of tuberoinfundibular
tract
 Hematological problems such as agranulocytosis
with atypical APMs (clozapine as the most
problematic agent).

21. Neurologic effects
 Pseudoparkinsonism: It is characterized by muscle rigidity,
shuffling gait, masklike facial expression, resting tremor.
 Acute dystonia: Prolonged muscle spasm. More common in
men younger than 40yrs. It may mimic seizure
 Akathisia: Subjective feeling of motor restlessness.
 Tardive dyskinesia: A disorder that involves involuntary,
repetitive movements of the muscles of the tongue, face and
body. You treat with low potency or atypical APMs.

22.  Neuroleptic malignant syndrome: A rare but
potentially life-threatening reaction to APMs. It
causes fever, muscular rigidity, altered mental status,
excessive sweating, salivation, increased BP and
pulse rate. It is treated by stopping the agent and
providing medical support.

23. Thank You