All of the AP drugs have some effect on D₂ receptor.Many atypical AP's are 5-HT_2A inverse agonsts. No evidence indicaing that antagonism of any DA receptor other than D2 plays a role in anipsychotic action.Most atypical and some of the typicals have a higher affinity for the 5-HT_2A receptor than the D₂ receptor. Some can also antagonize α2 adrenoceptors

• Aliphatic derivative (less potent, but more sedation and weight gain).
  
• It has very strong anticholinergic (M₁) effect and should be avoided in elderly.
• causes deposits in the anterior portion of the eye, accentuate normal aging of the lens
  
• α₁-blockade →orthostatic hypotension
• H₁ - antagonism→ sedation (some tolerance can develop; rebound insomnia/sleep disturbance)
• H₁augmented by 5-HT_2C blockade - weight gain
• seizure risk
• can cause cholestatic jaundice (rare) and skin rxns/photosensitivity
• treatment for uncontrolled hiccups
• inhibits CYP2D6
  

α1=5-­HT2A>D2>D1

• Piperidine Derivative (less potent)
• can cause retinal deposits that are associated with "browning" of vision (max doses are limited to reduce this ADR)
  
• H₁/5-HT_2Cantagonism -but more sedation and weight gain
• black box warning regarding torsade/fatal arrhythmias
• inhibits Na⁺channels and at higher doses Ca²⁺channels
• has no antiemetc effect
• inhibits CYP 2D6
  

• Piperazine derivatives (more potent and selective in their Pharmacological effects)
• Fluphenazine is availabel in long acting injectable formulation
• Perphenazine inhibits CYP2D6

Thioxanthene derivatives (potent)

Typical

• Most widely used typical  drug
• Diphenylbutylpiperidines (pimozide) are closely relatedcompounds.
• Compared to phenothiazines, butyrophenones and congeners: Tend to be more potent; Tend to have fewer autonomic effects;  Tend to have greater EPS.
• black box warning regarding torsade/fatal arrhythmias
• available in a long acting injectable form
  

D₂>α₁>D₄>5-HT_2A>D₁>H₁

• "Newish" typical, used for Tourette Syndrome
• black box warning regarding torsade/fatal arrhythmias

• 1st Atypical. It is considered a 2nd -line. Clozapine has unique effectiveness in refractory disease.
• used in the patients with suicide attempt history
  
• Lower risk of hyperprolactinemia. It has a very strong antimuscarinic effect (M₁) and should be avoided in elderly. 
• It is also M₄ agonist - causes Sialorrhea
• α₁- blockade → orthostatic hypotension
• H₁; H₁/5-HT_2c antagonism - sedation; weight gain (some tolerance; rebound insomnia/sleep disturbance)
• 3-5% seizure risk
• associated with myocarditis
• 1% develop agranulocytosis (reversible, can't be rechallenged)
• not approved for acute mania
• levels drop by 50% in smokers
• should never be discontinued abruptly unless it's  an emergency
  

D4=α1>5-­HT2A>D2=D1

Atypical, but classified as typical sometimes. It is closely related to Clozapine, however it's active metabolite causes EPS like typical drugs

• Atypical (FDA 2009)
• not extensively metabolized

• New Atypical
• Not approved for acute mania

• Atypical, 2nd line drug
• high doses have effectiveness in refractory disease
  
• H₁/5-HT_2c antagonism →weight gain
• H₁antagonism alone - sedation
• dyslipidemia -reversible upon discontinuation
  
• hyperglycemia, impaired glycemic control  - Usually reversible
• approved as monotherapy for maintenance of mania
• available in a long acting injectable form
• w/fluoxitine approved for bipolar depression
  

• Atypical.
  
• Its metabolite has antimuscarinic effect (M₁), but not as storng as Clozapine and Chlorpomazine.
• dyslipidemia, but not as much as with clozapine/olanzapine
• hyperglycemia - much lower than with clozapine/olanzapine
• H₁antagonism - sedation
• effective as monotherapy for bipolar depression (NE reuptake inhibition), also effective in trials for unipolar depression
  

• Atypical.
  
• Risperidone is an active metabolite of Paliperidone  (except 10%people who are poor metabolizers).
  
• Unlike other atypicals, they have higher risk of hyperprolactinemia.
• hyperglycemia and dyslipidemia -some risk, but not as much as with clozapine/olanzapine (both usually reversible)
• Resperidone (inject) is approved as  maintenance monotherapy for mania
  
• Resperidone approved for irritability in autism
  

• Atypical
• not extensively metabolized

Atypical. Partial D₂ agonist. 90%  D₂ occupancy; It gains its efficacy thorough 5-HT_2Aantagonism and maybe 5-HT_1Apartial agonism. Has a low risk of hyperprolactinemia.

• Phenothiazine
• Storng H₁ antagonism - used for insomnia and preoperative sedation

• used in neuroleptanesthesia (with fentanyl)
• used in postoperative to decrease N&V

• primarily prompted as antiemetic