Neuroleptics, adenylate cyclase inhibition

Two types of dopamine receptors have been characterized in the mammalian brain, termed and D2. This subtyping largely arose in response to the finding that while all types of clinically useful neuroleptics inhibit dopaminergic transmission in the brain, there is a poor correlation between reduction in adenylate cyclase activity, believed to be the second messenger linked to dopamine receptors, and the clinical potency of the drugs. This was particularly true for the butyrophenone series (e.g. haloperidol) which are known to be potent neuroleptics and yet are relatively poor at inhibiting adenylate cyclase. 

The H2-stimulated adenylate cyclase response is sensitive to inhibition by a range of psychotropic drugs. A large number of neuroleptic drugs are effective inhibitors of histamine-stimulated cyclase activity in rabbit cerebral cortex [158, 192] and guinea-pig hippocampus and cerebral cortex [81, 193]. The most potent compounds in homogenates of guinea-pig hippocampus appear to... 

---