D2 antagonist

D2 dopamine receptor antagonist

If BBB-crossing:
Mesolimbic blockade → ↓ aberrant salience/positive symptoms
Nigrostriatal blockade → EPS
Extrapyramidal symptoms (EPS) – D2 blockade in nigrostriatal pathway → relative acetylcholine excess
Tranquilization without sedation
Cortical effect – mesocortical D2 blockade
may worsen negative/cognitive symptoms
Antimanic – dampens dopaminergic hyperactivity in mesolimbic and mesocortical circuits
prokinetic also – D2 blockade in myenteric plexus → disinhibits ACh release → ↑ gastric emptying and duodenal peristalsis
Tuberoinfundibular blockade → ↑ prolactin
Prolactin elevation – tuberoinfundibular D2 blockade → removal of DA’s tonic inhibition of pituitary lactotrophs
Chemoreceptor trigger-zone blockade → antiemetic effect
Alternative splicing of the DRD2 gene produces two isoforms: D2S (short) and D2L (long)
high efficacy in schizophrenia
atypical clinical profile despite minimal 5-HT2A blockade D2S isoform-preferring D2 blocker

Drugs with this mechanism (62)