Professional Documents
Culture Documents
The therapeutic action of typical antipsychotic drugs not certain, but is correlated best
with antagonist activity at postjunctional dopamine (DA) D2-receptors in mesolimbic
and mesocortical areas of the CNS where DA normally inhibits adenylyl cyclase activity
Marc Imhotep Cray, M.D. Modified from: Lippincott Illustrated Reviews-Pharmacology Sixth Edition. 2015 16
CNS Pharmacology
Lecture 5
Antipsychotic Drugs (5)
Antipsychotic drugs block at dopaminergic and serotonergic receptors as
well as at adrenergic, cholinergic, and histamine binding receptors
Typical drugs:
Phenothiazines include:
Chlorpromazine (Thorazine) and thioridazine (Mellaril), which are
low potency phenothiazines
Fluphenazine (Prolixin) which is a high-potency phenothiazine
Toxicity:
Neuroleptic malignant syndrome (NMS) is a rare but severe
idiosyncratic reaction to antipsychotic medication
(20% mortality rate)
Syndrome is characterized by autonomic instability, muscle For NMS, think FEVER:
Fever
rigidity, diaphoresis, profound hyperthermia, and Encephalopathy
myoglobinuria Vitals unstable
Tx-antipsychotic should be discontinued and supportive Enzymes increase
care given along with bromocriptine to overcome DA Rigidity of muscles
receptor blockade, muscle relaxants such as diazepam or
dantrolene to reduce muscle rigidity
Pharmacokinetics:
These drugs are very long acting
Binding to many tissues results in a large Vd
Many drug metabolites due to extensive metabolism in liver
Marc Imhotep Cray, M.D. 23
CNS Pharmacology
Lecture 5
Other Uses of Antipsychotic Drugs:
Manic phase in bipolar disorder
Schizoaffective disorders
Atypical psychotic disorders
Depression with psychotic manifestations
Tourette syndrome (haloperidol, pimozide [Orap] or risperidone)
Severe nausea or vomiting associated with, e.g., radiation
treatment and cancer chemotherapy, as well as postoperative
nausea and vomiting
With the exception of thioridazine, typical antipsychotic
agents have strong antiemetic activity due to DA D2-receptor
blockade in chemoreceptor trigger zone (CTZ) of medulla
o most commonly used are phenothiazines prochlorperazine
and promethazine (both are void of antipsychotic activity)
THE END
Lectures/discussions to follow:
6. Drugs Affecting Movement Disorders and
Other Neurodegenerative Disorders
7. Analgesics
8. Anesthetics