Typical Antipsychotics

(High Potency vs. Low Potency)

- Clozapine

- Risperidone

- Quetiapine

- Olanzapine

- Ziprasidone

- Aripiprazole

- Paliperidone

- Asenapine

- Iloperidone

- First line therapy

- Lower incidence of EP side effx

- Used to tx levodopa-induced & AD-related psychoses

- Augmentation therapy for tx-resistant depression

- May be effective in pts. not receiving benefit from 1st generation agents

- May be substituted for 1st generation when signs of Tardive Dyskinesia appear

Atypical Antipsychotics

(Side Effects)

- Wt. gain 

- Hyperglycemia

(previous 2 decrease compliance)

- QT prolongation

- Sedation

- Somnolence, dizziness, constipation, postural hypotension, dry mouth

- Mortality risk in dementia-related psychosis

- Suicidality risk if indicated for depression

Clozapine (Clozaril)

5-HT₂>D₂ (D_4, D₃ > D₂);

Also H₁; α₁ and M₁ receptors; 

Selectivity for limbic site (D₃ localization)

- may be most effective antipsychotic but use limited by agranulocytosis (compromise immune system, sever leukopenia)

- sedative effx high

• 5-HT₂ > D₂ 
• Also H₁
• α₁ and M₁ receptors
• Selectivity for limbic (D₃ localization)

• Potent 5-HT_2A antagonist with an affinity for 5-HT₂ receptors an order of magnitude greater than observed for D₂ receptors
• High affinity for the 5-HT_1A, 5-HT_1D and 5-HT_2C 
• Less potent α₁ antagonist than clozapine
• Less affinit for the H1 and M1 receptors than clozapine
• Better anxiolysis or antidepressant action
• Low potential for impairing cognitive abilities; useful in AD 

• 5-HT2 > D2
• H1
• α1 & α2 adrenergic receptors

• D1, D2 & D4
• 5-HT2, 5-HT3
• H1
• α1 
• M1

• Partial agonist for D2 (only one) & 5-HT1A receptors
• Useful in treatment of bipolar disorder

• 5-HT2A > D2
• D3 & D4
• 5-HT6 & 5-HT7
• α1 & α2 adrenergic receptors

• 5-HT2 > D2
• Low/no affinity for other receptors