Psychopharmacology:

Central Nervous System Drugs II

AP Dr Ahmad Rohi Ghazali

OUTLINE
Central Nervous System Drugs

CNS Depressants

Anxiolytics

Neuroleptics

CNS Stimulants

ANALEPTICS

PSYCHOSTIMULANTS
Opioids
PSYCHODYSLEPTICS

CNS DEPRESSANTS :
OPIOIDS

BACKGROUND:
OPIUM:
poppy juice extracts Papaver somniferum.
medical (diarrhea & pain) + social uses.
about 20 & more active alkaloids.
Opioid:
substances with morphine-like effects.
antagonism with naloxone.
enkephalin, endorphin + dynorphin +
Synthetic analogues).
Opiate:
morphine derivative drugs.
similar chemical structure to morphine.
NOT including endogenous neuropeptides.

Morphine:

OPIUM:
1% Papaverine, 6% Narcotine,
10% Morphine + 0.5% Codein.
The structure of morphine + all
opium derivatives are
characterized by the piperidine
ring.
Pharmacological effects:
Analgesic (antinociceptive)
antidiarrhea
physical dependence
respiratory depression
Hydrophilic compared to heroin

Mechanism of Action, MOA of Opioid:

Pharmacological Responses of Opioid Sub Receptors :

Receptor Type

Analgesia
Supraspinal
Spinal
Peripheral

++ / ++ / ++
++ / -

+
++

Respiratory
Depression

++

Pupil (eye)

Constriction

Dilatation

GIT Motility

Smooth Muscle
Spasm

++

Behaviour / Emotion

Euphoria ++
Sedation ++

Dysphoria +
Sedation +

Dysphoria ++
Psychotomimetic

Physical Dependence

++

Receptor Type

Compounds

Opioid Peptides:
Beta-endorphin
Leu-enkaphalin
Dynorphin

+++
+
++

+++
+++
+

+++
+++

True Agonist:
Morphine
Codein
Pethidine
Etorphine
Fentanyl

+++
+
++
+++
+++

+
+
+
+++
+

++
+
+
+++
-

Partial Agonist :
Pentazocine
Nalorphine
Buprenorphine

(+)
(++)
+++

+
++
-

++
++
(++)

+
+
-

Antagonist:
Naloxone
Naltrexone

(+++)
(+++)

(++)
(++)

(++)
(++)

Opioids Adverse Reactions:

Major side effects are:
constipation + respiratory depression.

Sedation, GIT motility, nausea and vomiting.

Histamine release.
Tolerance also physical and psychological dependence.
Withdrawal: flu-like syndrome, yawn, runny nose,
hypertension, diarrhea, muscle spasm, fever and anxiety.
(Heroin:3-7 days, Methadone: 10-21 days).
OD Treatment:
Naloxone (Narcan) IV and Naltrexone (long acting).
Contraindication: respiratory depression, chronic lung
disease, liver or kidney disease, prostatic hypertrophy.

Other Opioids:
Diamorphine:
Heroin, Diacetylmorphine
vinegar smell & v lipophilic (BBB)

Codein:
3-methylmorphine+ antitussive (analgesic)
only 20% analgesia (NO euphoria)
Pethidine (DEMEROL):
NO sedation and antitussive effects.
antimuscarinic & analgesia (giving birth)
Fentanyl (China White) and Sufentanyl:
Short acting anaesthesia + ABUSE
(OD: rapid respiratory paralysis)
Etorphine:
Potency 1000X and tranquilizer

Pentazocine:

partial agonist: agonist / antagonist

arteriole BP
dependence + acute toxicity
very dysphoric + hallucination, nightmares
Buprenorphine:
structurally similar to Etorphine
BUT pharmacological responses are similar to Pentazocine.
Naloxone:
a pure opiate antagonist and prevents or reverses the
effects of opioids including respiratory depression, sedation
and hypotension.

Methadone:

effects similar to morphine, long acting

(t 1/2 = 15 -20 h) ie. highly bound + slowly
excreted.

sedative effects and physical

abstinence syndrome
heroin addiction alternative treatment +
morphine (oral)

(+ morphine / heroin injections, at low

doses, NO euphoria)
Mitragyna Speciosa, Ketom, Biak-biak:

Alternative treatment for heroin / opium

(replacement)?.
No naloxone activity

HAVE A BREAK!

CNS
DEPRESSANTS :
ANTIPSYCHOTIC
DRUGS

Fertility goddess of harvest and corn, sister of

Zeus, Demeter in agricultural societies.

 Antipsychotic drugs are also known as neuroleptic

drugs, antiSchizhoprenia or major tranquilizers.
Schizo(split) /phrenia (mind) :
1% world population.
Positive Symptoms (+): ACUTE
delusion, thought disturbances,
speech abnormalities, inner voices
and hallucination.
Negative Symptoms (-): CHRONIC
self-isolation (paranoid), less
emotional response and slow
mental and physical reaction (eg.
dementia).
Causes : combination genetic, environment
(anxiety + stress) + neurobiology (excess dopamine)

Dopamine Receptor Subtypes:

D1
Function

D1

D2

D5 D2 D3 D4

Distribution:
Cortex

Arousal, mood

+++

++

Limbic System

Emotion,
stereotype
behaviour

+++

++

Striatum

Motor Control

+++

++

Ventral
Hypothalamus +
Anterior pituitary

Prolactin
modulation

++

AntiSchizophrenia Drugs:
Classification of Antipsychotic Drugs:
Typical
Conventional (non-selective)
Block both dopamine and serotonin receptors
Cause several adverse effects eg. hypotension,
anticholinergic effects, extrapyramidal side effects
(EPS) eg. Chlorpozamine, Haloperidol
Atypical
Selective dopamine receptors
Primarily dopamine receptor blockers
May alleviate some of unpleasant effects
eg. Sulpiride, Clozapine

MOA of Neuroleptic Drugs:

More antagonisme at the dopamine receptor D2.
Also antagonisme at other monoamine receptors eg.
NAd, histamine, ACh and 5-HT.
neuroleptic side effects are from the actions on
other receptors than dopamine.
Onset time is long (days to weeks) and probable increase
of dopamine receptors may occur.

MOA of Neuroleptic Drugs:

Pharmacological Responses and Side Effects:

Antiemesis:
(+ cancer treatment, renal failure and pregnant mothers).
Endocrine effects:
serum prolactin concentration (gynaecomastia).
growth hormone secretion.
Others:
Effects from monoamine receptors inhibition:
M U S C A R I N E
Cardiovascular effects:
Vasodilatation, hypotension.
Idiosyncratic Effects and Hypersensitivity:
Jaundice (Chlorpromazine).
Leukopenia + agranulocytosis.
Skin reaction eg. Urticaria.

Extrapyramidal Syndrome (EPS):

PseudoParkinsonism (reversible and acute):
Tremor, dystonia, and muscle spasm
Direct inhibition at nigrostriatal receptors.
Tardive dyskinesia:
Involuntarily movement inhibition
Rabbit Syndrome
proliferation of dopamine receptors
at corpus striatum.

Tardive dyskinesia incidence is less occurring with

atypical drugs (Clozapine, Sulpiride).

A BEAUTIFUL MIND
SCHIZOPHRENIA IS FOR LIFE
There is no remission

SUMMARY: EFFECTS OF OPIOIDS

B A D

A M E R I C A N S :
B-Bradycardia and hypotension
A-Antitussive effect
D-Deep tendon reflexes are Depressed.

A-Analgesic effect
M-Miosis
E-Euphoria
R-Respiratory depression
I-Intracranial pressure is increased.
C-Constipation
A-Acute intoxication, Anaphylaxis - respiratory Acidosis,
N-Nausea and vomiting
S-Sedation

Drugs

Receptor Affinity

Side Effects

D1

D2

H1

mACh

5HT

EPS

Se

HiT

Chlorpromazine

++

+++

++

++

++

++

++

++

Haloperidol

+++

++

+/-

+++

++

Typical:

Lain2

Prolactin,
hypothermia,
anticholinergic,
hypersensitivity +
JAUNDICE.
SAME (NO jaundice
+ anticholinergic).

Flupenthixol

++

+++

++

+++

++

Atypical:
Sulpiride

Prolactin, anxiety.

Prolactin.
-

+++

Clozapine

++

++

++

++

+++

++

Quetiapine

+++

++

++

Notes

Risk of
agranulocytosis (1%).
Epilepsy. Sedation.
Saliva.
Anticholinergicity
effects.
Body weight.
Tachyicardia.
Agitation. Dry mouth.
Body weight.

Phenothiazine group (same with

Fluphenazine but no jaundice,
hypotension, EPS.

Butyrophenone group. Usual

Neuroleptic. EPS.

Same with Clopenthixol. Depot

preparation.
Benzamide group (same with
Pimozide). Selective towards
D2/3. absorption. EPS.
Dibenzodiazepine group (same
with Olanzepine but no risk of
agranulocytosis). Also at D4. NO
EPS. Effective for symptoms +/Schizophrenia. Suitable for
resistant patients to treatment.
Novel type. At alphaadrenoreceptor. Still under study.

THANK YOU