2-Antipsychotic Drugs
A- Intro
1- Psychosis: a mental illness characterized by
disturbed or non-existing reality.
: Types/ revision of
schizophrenia.
2- Dopamine hypothesis: Aided our understanding of how psychosis happen through the
synthesis of some drugs like Chlorpromazine and Haloperidol.
‣ Chlorpromazine -> post-synaptic D2 antagonism -> effective for Tx of schizophrenia.
( This drug was the bases for the hypothesis )
‣ Reserpine -> Depletion of monoamines in the pre-synaptic terminal -> antipsychotic effect.
( derived from Rauwol a )
‣ Cocaine, amphetamine, L-dopa -> Increased synaptic DA -> Drug induced psychosis.
‣ This theory was the bases for the development of rst-generation antipsychotic drugs which
differ in potency but share that they cause D2 blockade and a risk for extrapyramidal side
effects.
‣ Limitations:
• Doesn't Explain the cognitive de cits that appear to be related with low DA in the prefrontal
cortex.
• Doesn't Explain the antipsychotic effect of other pathways like serotonin and NMDA
antagonists.
, 3- Serotonin Hypothesis:
‣ Discovery that some hallucinogens are serotonin agonists -> research?? -> Not useful info.
BUTTTTT we discovered that 5-HT2A and possibly C are the cause for the hallucinatory effect of
these agents.
‣ 5-HT2A :
• These receptors mediate the release of DA, NE, ACh, glutamate and GABA in the cortex,
limbic region and the striatum. It also cause the depolarization of Glutamate Neurons but
stabilize NMDA receptors on the port-synaptic receptors.
• Clozapine -> 5-HT2A antagonist -> antipsychotic effect ( the prototype of Atypical antipsych
drugs )
‣ 5-HT2C
• Its stimulation inhibit cortical DA release -> many atypical antipsych drugs are antagonists.
A- Intro
1- Psychosis: a mental illness characterized by
disturbed or non-existing reality.
: Types/ revision of
schizophrenia.
2- Dopamine hypothesis: Aided our understanding of how psychosis happen through the
synthesis of some drugs like Chlorpromazine and Haloperidol.
‣ Chlorpromazine -> post-synaptic D2 antagonism -> effective for Tx of schizophrenia.
( This drug was the bases for the hypothesis )
‣ Reserpine -> Depletion of monoamines in the pre-synaptic terminal -> antipsychotic effect.
( derived from Rauwol a )
‣ Cocaine, amphetamine, L-dopa -> Increased synaptic DA -> Drug induced psychosis.
‣ This theory was the bases for the development of rst-generation antipsychotic drugs which
differ in potency but share that they cause D2 blockade and a risk for extrapyramidal side
effects.
‣ Limitations:
• Doesn't Explain the cognitive de cits that appear to be related with low DA in the prefrontal
cortex.
• Doesn't Explain the antipsychotic effect of other pathways like serotonin and NMDA
antagonists.
, 3- Serotonin Hypothesis:
‣ Discovery that some hallucinogens are serotonin agonists -> research?? -> Not useful info.
BUTTTTT we discovered that 5-HT2A and possibly C are the cause for the hallucinatory effect of
these agents.
‣ 5-HT2A :
• These receptors mediate the release of DA, NE, ACh, glutamate and GABA in the cortex,
limbic region and the striatum. It also cause the depolarization of Glutamate Neurons but
stabilize NMDA receptors on the port-synaptic receptors.
• Clozapine -> 5-HT2A antagonist -> antipsychotic effect ( the prototype of Atypical antipsych
drugs )
‣ 5-HT2C
• Its stimulation inhibit cortical DA release -> many atypical antipsych drugs are antagonists.
