PHRM 311 Lecture Notes - Lecture 13: Domperidone, Chlorpromazine, Brainstem
Document Summary
First gen (typical) antipsychotics phenothiazines, butyrophenones, benzamides. Second generation (atypical) antipsychotics benzazepines, benzisoxazoles & benzisothiazoles, arylpiperazine quinolone. Preferred dopamine conformation is trans ( > ) for d1- and d2- type dopamine receptors as demonstrated for these rigid agonists. D1- & d5-type receptors are excitatory (i. e. stimulate adenylyl cyclase) D2- , d3-, & d4-type receptors are inhibitory (i. e. inhibit adenylyl cyclase) Striatal dopamine stimulation of direct & indirect pathways modulates thalamus excitatory outflow to the motor cortex. Approaches (e. g. antagonism) to reduce this effect will alleviate psychotic symptoms. Average daily dose of antipsychotic drug was found to inversely correlate with affinity toward the d2-type da receptor (eps effects correlate as well). Change from 2 to 3 methylenes improved antipsychotic activity. Phenothiazine & butyrophenone interactions: affinity for d2 greater than affinity toward d1 and 5-ht2a gpcrs. Benzamides also enhance gi motility used in treating eating disorders.
